29 votes
Posted 30 June 2015 - 07:53 PM
Lostfalco are you still using tadalafil drops from superiorpeptides? Do consider it a quality and safe product?
Hey, magta...yeah, that's what I've been using. I've had no problems with them at all but there is some guesswork involved. I haven't done a chemical analysis on their products or anything but they seem pretty effective to me. Of course, feel free to use a more trusted source if you have one. =)
OK so I have been using 1 or 2 drops per day for 3 weeks, really like its effects!
Posted 09 July 2015 - 08:52 PM
Disclaimer: clenbuterol is very dangerous and I am NOT recommending it's use.
However, clenbuterol does raise cAMP and significantly improves memory in rats. Clen builds tolerance quickly and can have detrimental effects on the heart...so that must be kept in mind. Bodybuilders use it to cut fat while maintaining muscle mass because it is mildly anabolic. It has been combined with PDE4 inhibitors in rats with synergistic effects on cAMP levels and memory. Surprisingly (to me, at least) it's also anti-inflammatory in the brain. Just sharing some research. =)
http://www.ncbi.nlm....pubmed/23596314
Learn Mem. 2013 Apr 17;20(5):274-84. doi: 10.1101/lm.030411.113.
Activation of β2-adrenoceptor enhances synaptic potentiation and behavioral memory via cAMP-PKA signaling in the medial prefrontal cortex of rats.
The prefrontal cortex (PFC) plays a critical role in cognitive functions, including working memory, attention regulation, behavioral inhibition, as well as memory storage. The functions of PFC are very sensitive to norepinephrine (NE), and even low levels of endogenously released NE exert a dramatic influence on the functioning of the PFC. Activation of β-adrenoceptors (β-ARs) facilitates synaptic potentiation and enhances memory in the hippocampus. However, little is known regarding these processes in the PFC. In the present study, we investigate the role of β2-AR in synaptic plasticity and behavioral memory. Our results show that β2-AR selective agonist clenbuterol facilitates spike-timing-dependent long-term potentiation (tLTP) under the physiological conditions with intact GABAergic inhibition, and such facilitation is prevented by co-application with the cAMP inhibitor Rp-cAMPS. Loading postsynaptic pyramidal cells with Rp-cAMPS, the PKA inhibitor PKI(5-24), or the G protein inhibitor GDP-β-S significantly decreases, but does not eliminate, the effect of clenbuterol. Clenbuterol suppresses the GABAergic transmission, while blocking GABAergic transmission by the GABA(A) receptor blocker partially mimics the effect of clenbuterol. In behavioral tests, a post-training infusion of clenbuterol into mPFC enhances 24-h trace fear memory. In summary, we observed that prefrontal cortical β2-AR activation by clenbuterol facilitates tLTP and enhances trace fear memory. The mechanism underlying tLTP facilitation involves stimulating postsynaptic cAMP-PKA signaling cascades and suppressing GABAergic circuit activities.
http://www.ncbi.nlm....pubmed/21871511
Neurochem Int. 2011 Nov;59(6):837-46. doi: 10.1016/j.neuint.2011.08.012. Epub 2011 Aug 17.
Combined anti-inflammatory effects of β2-adrenergic agonists and PDE4 inhibitors on astrocytes by upregulation of intracellular cAMP.Inflammation is an important hallmark of all neurodegenerative diseases and activation of different glial populations may be involved in the progression of some of these disorders. Especially, the activation of astroglia can lead to long-term detrimental morphological changes, such as scar formation. Therefore, improved strategies to modulate inflammation in these cells are currently being investigated. We investigated the interaction of phosphodiesterase (PDE) 4 inhibitors, such as rolipram, with other agents raising cellular cAMP levels. When used alone, none of the PDE4 inhibitors increased cAMP levels. The adenylate cyclase activator forskolin, the β(2)-adrenergic agonist clenbuterol and the mixed β(1)/β(2)-adrenergic agonist isoproterenol increased intracellular cAMP levels of cortical murine astrocytes. This increase was synergistically elevated by rolipram or the PDE4inhibitor RO-201724, but not by inhibition of PDE3. Inflammatory stimulation of the cells with the cytokines TNF-α, IL-1β and IFN-γ strongly induced PDE4B and augmented overall PDE4 activity, while PDE3 activity was low. Clenbuterol and forskolin caused downregulation of cytokines and chemokines such as IL-6 and MCP-1. This effect was further enhanced by rolipram, but not by the PDE3 inhibitor milrinone. The cAMP-raising drug combinations attenuated the upregulation of TNF-α and IL-6 mRNA and the secretion of IL-6, but did not affect initial NF-κB signalling triggered by the stimulating cytokines. These results indicate that PDE4 may be a valuable anti-inflammatory target in brain diseases, especially under conditions associated with stimulation of cAMP-augmenting astrocyte receptors as is observed by clenbuterol treatment.
http://www.ncbi.nlm....pubmed/25196704
Neurobiol Learn Mem. 2014 Nov;115:49-57. doi: 10.1016/j.nlm.2014.08.016. Epub 2014 Sep 6.
Noradrenergic actions in the basolateral complex of the amygdala modulate Arc expression in hippocampal synapses and consolidation of aversive and non-aversive memory.
The basolateral complex of the amygdala (BLA) plays a role in the modulation of emotional memory consolidation through its interactions with other brain regions. In rats, memory enhancing infusions of the β-adrenergic receptor agonist clenbuterol into the BLA immediately after training enhances expression of the protein product of the immediate early gene Arc in the dorsal hippocampus and memory-impairing intra-BLA treatments reduce hippocampal Arc expression. We have proposed that the BLA may modulate memory consolidation through an influence on the local translation of synaptic plasticity proteins, like Arc, in recently active synapses in efferent brain regions. To date, all work related to this hypothesis is based on aversive memory tasks such as inhibitory avoidance (IA). To determine whether BLA modulation of hippocampal Arc protein expression is specific to plasticity associated with inhibitory avoidance memory, or a common mechanism for multiple types of memory, we tested the effect of intra-BLA infusions of clenbuterol on memory and hippocampal synaptic Arc expression following IA or object recognition training. Results indicate that intra-BLA infusions of clenbuterol enhance memory for both tasks; however, Arc expression in hippocampal synaptoneurosomes was significantly elevated only in rats trained on the aversive IA task. These findings suggest that regulation of Arc expression in hippocampal synapses may depend on co-activation of arousal systems. To test this hypothesis, a "high arousal" version of the OR task was used where rats were not habituated to the testing conditions. Posttraining intra-BLA infusions of clenbuterol enhanced consolidation of the high-arousing version of the task and significantly increased Arc protein levels in dorsal hippocampus synaptic fractions. These findings suggest that the BLA modulates multiple forms of memory and affects the synaptic plasticity-associated protein Arc in synapses of the dorsal hippocampus when emotional arousal is elevated.
http://www.ncbi.nlm....pubmed/25613546
Neurobiol Learn Mem. 2015 Mar;119:34-41. doi: 10.1016/j.nlm.2014.12.004. Epub 2015 Jan 19.
Memory-enhancing intra-basolateral amygdala clenbuterol infusion reduces post-burst afterhyperpolarizations in hippocampal CA1 pyramidal neurons following inhibitory avoidance learning.
Activation of the basolateral amygdala can modulate the strength of fear memories, including those in single-trial inhibitory avoidance (IA) tasks. Memory retention, measured by the latency to re-enter a dark-compartment paired 24h earlier with a footshock, varies with intensity of this aversive stimulus. When higher intensity footshocks were used, hippocampal CA1 pyramidal neurons exhibited reduced afterhyperpolarizations (AHPs) 24h post-trial, an effect blocked by immediate post-trial inactivation of the basolateral complex of the amygdala (BLA). Similar AHP reductions in CA1 have been observed in a number of learning tasks, with time courses appropriate to support memory consolidation. When less intense footshocks were used for IA training of Sprague-Dawley rats, immediate post-trial infusion of the β-adrenergic agonist clenbuterol into BLA was required to enhance hippocampal Arc protein expression 45 min later and to enhance memory retention tested 48 h later. Here, using Long-Evans rats and low-intensity footshocks, we confirmed that bilateral immediate post-trial infusion of 15 ng/0.5 μl of the β-adrenergic agonist clenbuterol into BLA significantly enhances memory for an IA task. Next, clenbuterolwas infused into one BLA immediately post-training, with vehicle infused into the contralateral BLA, then hippocampal CA1 neuron AHPs were assessed 24 h later. Only CA1 neurons from hemispheres ipsilateral to post-trial clenbuterol infusion showed learning-dependent AHP reductions. Excitability of CA1 neurons from the same trained rats, but from the vehicle-infused hemispheres, was identical to that from untrained rats receiving unilateral clenbuterol or vehicle infusions. Peak AHPs, medium and slow AHPs, and accommodation were reduced only with the combination of IA training and unilateral BLA β-receptor activation. Similar to previous observations of BLA adrenergic memory-related enhancement of Arc protein expression in hippocampus, increased CA1 neuronal excitability in the fear-modulated IA task was activated by immediate post-trial β-receptor activation of the ipsilateral BLA.
Edited by lostfalco, 09 July 2015 - 08:57 PM.
Posted 10 July 2015 - 05:01 PM
Mitochondria produce adenosine triphosphate (ATP), critical for cellular metabolism. ATP declines with age, which is associated with inflammation. Here, we measure retinal and brain ATP in normal C57BL/6 and complement factor H knockout mice (Cfh-/-), which are proposed as a model of age-related macular degeneration. We show a significant premature 30% decline in retinal ATP in Cfh-/- mice and a subsequent shift in expression of a heat shock protein that is predominantly mitochondrial (Hsp60). Changes in Hsp60 are associated with stress and neuroprotection. We find no differences in brain ATP between C57BL/6 and Cfh-/- mice. Near infrared (NIR) increases ATP and reduces inflammation. ATP decline in Cfh-/- mice was corrected with NIR which also shifted Hsp60 labeling patterns. ATP decline in Cfh-/- mice occurs before inflammation becomes established and photoreceptor loss occurs and may relate to disease etiology. However, ATP levels were corrected with NIR. In summary, we provide evidence for a mitochondrial basis for this disease in mice and correct this with simple light exposure known to improve mitochondrial function.
Posted 14 July 2015 - 03:08 AM
Rimonabant can cause depression but its mechanism of action is still very fascinating.
It is an inverse agonist (or antagonist depending on who you talk to) of the CB1 receptor and has been shown to significantly enhance LTP in rodents and cells. It pretty much has the exact opposite effects of smoking cannabis...it decreases appetite and improves memory. Unfortunately, it increases suicide risk which is why it was withdrawn from the European market in 2008 (it was marketed as an anti-obesity drug).
http://www.ncbi.nlm....les/PMC2882689/
Drug Dev Res. 2009 Dec 1;70(8):555-565.
Are CB(1) Receptor Antagonists Nootropic or Cognitive Impairing Agents?
For more than a decade, a considerable amount of research has examined the effects of rimonabant (SR 141716) and other CB(1) receptor antagonists in both in vivo and in vitro models of learning and memory. In addition to its utility in determining whether the effects of drugs are mediated though a CB(1) receptor mechanism of action, these antagonists are useful in providing insight into the physiological function of the endogenous cannabinoid system. Several groups have reported that CB(1) receptor antagonists enhance memory duration in a variety of spatial and operant paradigms, but not in all paradigms. Conversely, disruption of CB(1) receptor signaling also impairs extinction learning in which the animal actively suppresses a learned response when reinforcement has been withheld. These extinction deficits occur in aversively motivated tasks, such as in fear conditioning or escape behavior in the Morris water maze task, but not in appetitively motivated tasks. Similarly, in electrophysiological models, CB(1) receptor antagonists elicit a variety of effects, including enhancement of long-term potentiation (LTP), while disrupting long-term depression (LTD) and interfering with transient forms of plasticity, including depolarization-induced suppression of inhibition (DSI) and depolarization-induced suppression of excitation (DSE). The collective results of the in vivo and in vitro studies employing CB(1) receptor antagonists, demonstrate that these receptors play integral roles in different components of cognitive processing. Functionally, pharmacological blockade of CB(1) receptors may strengthen memory duration, but interferes with extinction of learned behaviors that are associated with traumatic or aversive memories.
Edited by lostfalco, 14 July 2015 - 03:14 AM.
Posted 19 July 2015 - 12:07 AM
I interviewed Dr Michael Hamblin and we discussed some very important topics in LLLT....take a gander!
http://selfhacked.co...therapy-expert/
Edited by Joe Cohen, 19 July 2015 - 12:07 AM.
Posted 20 July 2015 - 12:23 AM
Q: I emailed him an important question after the interview….Is there a problem using C60 olive oil with LLLT?No problem combining C60 in olive oil and LLLT.
Good news.
In my experiments with LLLT I've noticed that the effects of c60 with LLLT compared with LLLT alone are a bit different, for example for hair loss LLLT is better when is applied alone. I think that the best protocol is to take c60, in a low dose like 4mg a week, then wait for 4 - 5 days, then apply LLLT and the next day take c60 again (with 4 or 5 days some of the effects of c60 dissapear, for example alcohol tolerance, increased breath oxygenation). For me this is the better way to get the benefits from the two things, the days when c60 is in my body I can apply LLLT also.
Edited by BieraK, 20 July 2015 - 12:24 AM.
Posted 25 July 2015 - 11:49 PM
I asked hamblin and he said there shouldn't be any negative interaction with C60 and LLLT.
Yes Joe, I know that, I also think that there is no negative interaction between c60 and LLLT (Understanding negative in the sense of detrimental). When I emailed to Dr. Gonzalez-lima, he said that consumption of antioxidants such as NAC not interfere with LLLT.
I think there are three things that should be taken into account:
It is not known what is the exact mechanism of action c60.
There are studies that talk about the disruptive effects of antioxidant consumption on the effects of exercise, for example delayed adaptation to ROS produced by exercise. (and LLLT works in part by a similar manner).
There are interesting reports in this forum about the interaction of LLLT and antioxidant supplementation, and with the use of c60, for example the following:
http://www.longecity...oo/#entry719804
As I said earlier, I have noticed differences between the application of LLLT alone, and the application of LLLT combined with other things, like c60.
The interaction between LLLT and c60 is not negative, however there is the possibility that some effects of LLLT can be blocked or delayed by intake of antioxidants, mito enhancers or mitoprotective agents. It is also possible that trough the combination of LLLT with supplements, it can be obtained effects that can't not be obtained with the usage of LLLT alone.
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I know this question has been performed many times, however it remains unclear to me
Considering the mechanism of action of LLLT. What can be the best time to apply it?
If this works similar to exercise, Could be better to apply LLLT in a fasted state, and then consume food? (Like the leangains protocol).
What do you think guys?
Edited by BieraK, 25 July 2015 - 11:59 PM.
Posted 05 August 2015 - 12:23 AM
I love having my mind blown by something I've never thought of before. I just had to share. =)
Astroglia invade synapses and prevent glutamate from reaching AMPA receptors.
Connexin 30 prevents astroglia from invading synapses.
Modafinil increases connexin 30.
http://www.nature.co...ll/nn.3662.html
Edited by lostfalco, 05 August 2015 - 12:25 AM.
Posted 05 August 2015 - 07:59 PM
Once we have astroglia out of the way, we can recruit more AMPA receptors to the post-synaptic neuron's surface.
Activating astroglial α7-containing nicotinic acetylcholine receptors (α7-nAChRs) adds extra AMPA receptors to the post-synaptic neuron (see pic below).
Acetylcholine, nicotine, etc...activate astroglial α7-containing nicotinic acetylcholine receptors.
Galantamine is a positive allosteric modulator of α7-containing nicotinic acetylcholine receptors.
Kynurenic acid blocks the allosteric potentiating site of the alpha7AChR. See this thread for more info http://www.longecity...ad/#entry716469
Note: AMPA receptor trafficking requires ATP to cause the movement (LLLT, Methylene Blue, etc.).
http://www.ncbi.nlm....les/PMC4222677/
J Neurochem. 2013 Dec;127(5):632-43. doi: 10.1111/jnc.12436. Epub 2013 Sep 30.
Activation of α7-containing nicotinic receptors on astrocytes triggers AMPA receptor recruitment to glutamatergic synapses.
Astrocytes, an abundant form of glia, are known to promote and modulate synaptic signaling between neurons. They also express α7-containing nicotinic acetylcholine receptors (α7-nAChRs), but the functional relevance of these receptors is unknown. We show here that stimulation of α7-nAChRs on astrocytes releases components that induce hippocampal neurons to acquire more α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors post-synaptically at glutamatergic synapses. The increase is specific in that no change is seen in synaptic NMDA receptor clusters or other markers for glutamatergic synapses, or in markers for GABAergic synapses. Moreover, the increases in AMPA receptors on the neuron surface are accompanied by increases in the frequency of spontaneous miniature synaptic currents mediated by the receptors and increases in the ratio of evoked synaptic currents mediated by AMPA versus NMDA receptors. This suggests that stimulating α7-nAChRs on astrocytes can convert 'silent' glutamatergic synapses to functional status. Astrocyte-derived thrombospondin is necessary but not sufficient for the effect, while tumor necrosis factor-α is sufficient but not necessary. The results identify astrocyte α7-nAChRs as a novel pathway through which nicotinic cholinergic signaling can promote the development of glutamatergic networks, recruiting AMPA receptors to post-synaptic sites and rendering the synapses more functional. We find that activation of nicotinic receptors on astrocytes releases a component that specifically recruits AMPA receptors to glutamatergic synapses. The recruitment appears to occur preferentially at what may be 'silent synapses', that is, synapses that have all the components required for glutamatergic transmission (including NMDA receptors) but lack sufficient AMPA receptors to generate a response. The results are unexpected and open up new possibilities for mechanisms underlying network formation and synaptic plasticity.
http://www.ncbi.nlm....pubmed/19690987
J Mol Neurosci. 2010 Jan;40(1-2):204-10. doi: 10.1007/s12031-009-9235-2. Epub 2009 Aug 19.
The astrocyte-derived alpha7 nicotinic receptor antagonist kynurenic acid controls extracellular glutamate levels in the prefrontal cortex.
The cognitive deficits seen in schizophrenia patients are likely related to abnormal glutamatergic and cholinergic neurotransmission in the prefrontal cortex. We hypothesized that these impairments may be secondary to increased levels of the astrocyte-derived metabolite kynurenic acid (KYNA), which inhibits alpha7 nicotinic acetylcholine receptors (alpha7AChR) and may thereby reduce glutamate release. Using in vivo microdialysis in unanesthetized rats, we show here that nanomolar concentrations of KYNA, infused directly or produced in situ from its bioprecursor kynurenine, significantly decrease extracellular glutamate levels in the prefrontal cortex. This effect was prevented by the systemic administration of galantamine (3 mg/kg) but not by donepezil (2 mg/kg), indicating that KYNA blocks the allosteric potentiating site of the alpha7AChR, which recognizes galantamine but not donepezil as an agonist. In separate rats, reduction of prefrontal KYNA formation by (S)-4-ethylsulfonyl benzoylalanine, a specific inhibitor of KYNA synthesis, caused a significant elevation in extracellular glutamate levels. Jointly, our results demonstrate that fluctuations in endogenous KYNA formation bidirectionally influence cortical glutamate concentrations. These findings suggest that selective attenuation of cerebral KYNA production, by increasing glutamatergic tone, might improve cognitive function in individuals with schizophrenia.
Edited by lostfalco, 06 August 2015 - 12:50 AM.
Posted 05 August 2015 - 08:06 PM
Now that we have more AMPA receptors at the surface of the post-synaptic neuron we can allosterically modulate them with ampakines (IDRA-21, Aniracetam, etc.).
Note: I am VERY aware of excitotoxicity issues here...proceed with caution. =)
Posted 05 August 2015 - 08:25 PM
Now that your receptors are ridiculously optimized for learning...use this form of spaced repetition learning.
Study for 20 minutes, take a break for 10 minutes, study for 20 minutes, break for 10 minutes, study for 20 minutes = total 80 minutes.
Note: Go over the exact same notes during each 20 minute study time.
Note 2: DO NOT think about the notes during your 10 minute break times. Do something COMPLETELY unrelated like juggling, walking your dog, or juggling your dog.
Note 3: Use a countdown timer to time yourself.
Note 4: Be prepared to be blown away by how much you can remember!
http://www.ncbi.nlm....les/PMC3782739/
Front Hum Neurosci. 2013 Sep 25;7:589. doi: 10.3389/fnhum.2013.00589. eCollection 2013.
Making long-term memories in minutes: a spaced learning pattern from memory research in education.
Memory systems select from environmental stimuli those to encode permanently. Repeated stimuli separated by timed spaces without stimuli can initiate Long-Term Potentiation (LTP) and long-term memory (LTM) encoding. These processes occur in time scales of minutes, and have been demonstrated in many species. This study reports on using a specific timed pattern of three repeated stimuli separated by 10 min spaces drawn from both behavioral and laboratory studies of LTP and LTM encoding. A technique was developed based on this pattern to test whether encoding complex information into LTM in students was possible using the pattern within a very short time scale. In an educational context, stimuli were periods of highly compressed instruction, and spaces were created through 10 min distractor activities. Spaced Learning in this form was used as the only means of instruction for a national curriculum Biology course, and led to very rapid LTM encoding as measured by the high-stakes test for the course. Remarkably, learning at a greatly increased speed and in a pattern that included deliberate distraction produced significantly higher scores than random answers (p < 0.00001) and scores were not significantly different for experimental groups (one hour spaced learning) and control groups (four months teaching). Thus learning per hour of instruction, as measured by the test, was significantly higher for the spaced learning groups (p < 0.00001). In a third condition, spaced learning was used to replace the end of course review for one of two examinations. Results showed significantly higher outcomes for the course using spaced learning (p < 0.0005). The implications of these findings and further areas for research are briefly considered.
Edited by lostfalco, 05 August 2015 - 08:32 PM.
Posted 06 August 2015 - 01:10 AM
I sense a new protocol coming soon [emoji1]
haha Indeed. A ton of the things we've discussed before such as PDEs, epigenetic modifications, lactate, cytoskeleton remodeling, etc. also play a role here.
I think the main reason that many people don't notice enhancements from a lot of the memory supplements is that they are not taking into account the fact that the brain is a temporal memory system (which I've mentioned before...see Jeff Hawkins' work on HTM). The 20/10 studying system really allows many of these enhancements to become noticeable. There is no look-at-something-once-and-remember-it-forever kind of thing going on. That's for movies and TV. It just doesn't make evolutionary sense for our brain to remember everything. It's too energetically costly and our brains would quickly run out of storage (we are bombarded by an unimaginable amount of data on a daily basis). The brain remembers things that it's repeatedly exposed to and forgets things that don't recur. Early on in the memory process this involves receptor trafficking (which we've just focused on) while later it involves protein transcription (in my humble opinion 
). Once an AMPA receptor is trafficked to the synapse you have to reactivate it before it gets trafficked out. All the ampakines in the world are not going to help you if you don't study properly.
Edited by lostfalco, 06 August 2015 - 01:15 AM.
Posted 06 August 2015 - 12:35 PM
lostfalco, how do you think this 20/10 method compares with just doing anki every day? Is there a way to combine them? I got brainscape on my phone for srs and so far its pretty good, but I am always open to optimize.
Hey alpal, I think they can definitely be combined. Use 20/10 for acquisition on day one and then the typical Anki spaced repetition review schedule from that point on for maintenance. Ebbinghaus would be proud. =)
Posted 09 August 2015 - 07:36 AM
Now that your receptors are ridiculously optimized for learning...use this form of spaced repetition learning.
Study for 20 minutes, take a break for 10 minutes, study for 20 minutes, break for 10 minutes, study for 20 minutes = total 80 minutes.
Note: Go over the exact same notes during each 20 minute study time.
Note 2: DO NOT think about the notes during your 10 minute break times. Do something COMPLETELY unrelated like juggling, walking your dog, or juggling your dog.
Note 3: Use a countdown timer to time yourself.
Note 4: Be prepared to be blown away by how much you can remember!
http://www.ncbi.nlm....les/PMC3782739/
Front Hum Neurosci. 2013 Sep 25;7:589. doi: 10.3389/fnhum.2013.00589. eCollection 2013.
Making long-term memories in minutes: a spaced learning pattern from memory research in education.
AbstractMemory systems select from environmental stimuli those to encode permanently. Repeated stimuli separated by timed spaces without stimuli can initiate Long-Term Potentiation (LTP) and long-term memory (LTM) encoding. These processes occur in time scales of minutes, and have been demonstrated in many species. This study reports on using a specific timed pattern of three repeated stimuli separated by 10 min spaces drawn from both behavioral and laboratory studies of LTP and LTM encoding. A technique was developed based on this pattern to test whether encoding complex information into LTM in students was possible using the pattern within a very short time scale. In an educational context, stimuli were periods of highly compressed instruction, and spaces were created through 10 min distractor activities. Spaced Learning in this form was used as the only means of instruction for a national curriculum Biology course, and led to very rapid LTM encoding as measured by the high-stakes test for the course. Remarkably, learning at a greatly increased speed and in a pattern that included deliberate distraction produced significantly higher scores than random answers (p < 0.00001) and scores were not significantly different for experimental groups (one hour spaced learning) and control groups (four months teaching). Thus learning per hour of instruction, as measured by the test, was significantly higher for the spaced learning groups (p < 0.00001). In a third condition, spaced learning was used to replace the end of course review for one of two examinations. Results showed significantly higher outcomes for the course using spaced learning (p < 0.0005). The implications of these findings and further areas for research are briefly considered.
That's interesting, but I don't quite understand how it actually works. The first exposure of any study material usually takes longer to grasp, but the second exposure would take shorter time to go through (the same material). How do you actually apply 20/10/20/10/20? or is it possible this is only apply to rote memorization of materials (understanding already been done), such as tables? How is that compared to mnemonic techniques in term of effectiveness? Sorry for so many questions
Posted 09 August 2015 - 02:56 PM
That's interesting, but I don't quite understand how it actually works. The first exposure of any study material usually takes longer to grasp, but the second exposure would take shorter time to go through (the same material). How do you actually apply 20/10/20/10/20? or is it possible this is only apply to rote memorization of materials (understanding already been done), such as tables? How is that compared to mnemonic techniques in term of effectiveness? Sorry for so many questions
Hey Amorphous, no problem about the questions. =)
I use this technique primarily to study lecture notes from class. For me, each 20 min segment usually involves a mix of memorization and new understanding. If I only understand 80% on the first time through then I quickly go through that 80% on the second time through and focus on understanding the 20% that's a bit hazier. Then I study all of it the third time through.
You bring up a great point though...in my previous example I learned the 80% on pass 1 and reviewed it twice (on pass 2 and 3). I learned 20% of the material on pass 2 and only reviewed it once (on pass 3). Of course, if I understood 100% before I even looked at the notes then I would have reviewed 100% 3 times.
I would say that this technique is better for memorization but it certainly helps with understanding. In practice, you could always take an extra 10 minute break and add a fourth 20 minute study segment in which you focus on really getting that 20% (from my example) down. I'd say experiment and tweak and see what you discover. Would 10 minutes on, 5 minutes off work just as well? Test it out and see. (It's actually pretty effective in my experience). The science gives us some general directions to look in but experience is always a bit messier.
I've found the effectiveness of mnemonic techniques to be very limited in practice. That's just me though. Some people love them. Yep, it's time for that dreaded acronym again....ymmv.
Edited by lostfalco, 09 August 2015 - 02:57 PM.
Posted 09 August 2015 - 03:55 PM
This looks like an interesting study though it does not seem to be published yet.
FASEB J. 2015 Aug 7. pii: fj.15-275404. [Epub ahead of print]Mitochondrial-targeted antioxidants.AbstractRedox homeostasis is maintained by the antioxidant defense system, which is responsible for eliminating a wide range of oxidants, including reactive oxygen species (ROS), lipid peroxides, and metals. Mitochondrial (mt)-localized antioxidants are widely studied because the mitochondria; the major producer of intracellular ROS, has been linked to the cause of aging and other chronic diseases. Mt-targeted antioxidants have shown great potential because they cross the mt phospholipid bilayer and eliminate ROS at the heart of the source. Growing evidence has identified mt-targeted antioxidants, such as MitoQ and tiron as potentially effective antioxidant therapies against the damage caused by enhanced ROS generation. This literature review summarizes the current knowledge on mt-targeted antioxidants and their contribution to the body's antioxidant defense system. In addition to addressing the concerns surrounding current antioxidant strategies, including difficulties in targeting antioxidant treatment to sites of pathologic oxidative damage, we discuss promising therapeutic agents and new strategic approaches.-Oyewole, A. O., Birch-Machin, M. A. Mitochondrial-targeted antioxidants.
© FASEB.
Posted 09 August 2015 - 09:22 PM
Some PDE5 updates:
1. Sildenafil increases testosterone production.
2. Tadalafil decreases aromatase expression (aromatase converts testosterone to estrogen) and increases androgen receptor number.
http://www.ncbi.nlm....les/PMC2741156/
Int J Exp Pathol. 2009 Aug;90(4):454-62. doi: 10.1111/j.1365-2613.2009.00660.x.
Chronic treatment with sildenafil stimulates Leydig cell and testosterone secretion.
The phosphodiesterase type 5 (PDE5) inhibitor, Sildenafil, is a novel, oral treatment approach for pulmonary hypertension. As Leydig cells present PDE5, this study was conducted to investigate the effects of the chronic treatment with Sildenafil (25 mg/kg) on male Swiss Webster mice steroidogenesis. After a 4-week long experimental design, Leydig cells were analysed by morphological and immunocytochemical procedures. Serum testosterone was assayed by radioimmunoassay. Leydig cells presented noteworthy ultrastructural alterations, such as a vesicular smooth endoplasmic reticulum, large vacuoles scattered through the cytoplasm, enlarged mitochondria with discontinue cristaes and whorle membranes with vesicles at the periphery, which are typical characteristics of an activated steroid-secreting cell. Important immunocytochemical labelling for steroidogenic acute regulatory protein, cytochrome P450 side-chain cleavage enzyme and testosterone were detected in isolated Leydig cells. In addition, Sildenafil-treated mice showed significant increased levels of total testosterone. The results obtained in the present study are consistent with the hypothesis that the accumulation of cyclic guanosine monophosphate by PDE5 inhibition could be involved in the androgen biosynthesis stimulation. Important clinical implications of hormonal disorders should be taken into account for patients with pulmonary hypertension.
http://www.ncbi.nlm....pubmed/26134065
J Endocrinol Invest. 2015 Jul 2. [Epub ahead of print]
Tadalafil modulates aromatase activity and androgen receptor expression in a human osteoblastic cell in vitro model.
Phosphodiesterase type-5 inhibitor (PDE5i) tadalafil administration in men with erectile dysfunction is associated with increased testosterone/estradiol ratio, leading to hypothesize a potential increased effect of androgen action on target tissues. We aimed to characterize, in a cellular model system in vitro, the potential modulation of aromatase and sex steroid hormone receptors upon exposure to tadalafil (TAD).
METHODS:Human osteoblast-like cells SAOS-2 were chosen as an in vitro model system since osteoblasts are target of steroid hormones. Cells were tested for viability upon TAD exposure, which increased cell proliferation. Then, cells were treated with/without TAD for several times to evaluate potential modulation in PDE5, aromatase (ARO), androgen (AR) and estrogen (ER) receptor expression.
RESULTS:Osteoblasts express significant levels of both PDE5 mRNA and protein. Exposure of cells to increasing concentrations of TAD (10-8-10-7 M) decreased PDE5 mRNA and protein expression. Also, TAD inhibited ARO mRNA and protein expression leading to an increase in testosterone levels in the supernatants. Interestingly, TAD increased total AR mRNA and protein expression and decreased ERα, with an increased ratio of AR/ER, suggesting preferential androgenic vs estrogenic pathway activation.
CONCLUSIONS:Our results demonstrate for the first time that TAD decreases ARO expression and increases AR protein expression in human SAOS-2, strongly suggesting a new control of steroid hormones pathway by PDE5i. These findings might represent the first evidence of translational actions of PDE5i on AR, which leads to hypothesize a growing relevance of this molecule in men with prostate cancer long-term treated with TAD for sexual rehabilitation.
Edited by lostfalco, 09 August 2015 - 09:23 PM.
Posted 12 August 2015 - 11:43 PM
Another method for AMPA receptor trafficking: increase norepinephrine/glucocorticoids (ephedrine, prolintane, etc.).
Combine with an ampakine for a synergistic enhancement of learning (Idra-21, Aniracetam, etc.).
***Insert obligatory high risk warning here. =)
http://www.nature.co...ll/nrn2913.html
Nat Rev Neurosci. 2010 Oct;11(10):675-81. doi: 10.1038/nrn2913. Epub 2010 Sep 8.
Stress hormones and AMPA receptor trafficking in synaptic plasticity and memory.
The acquisition and consolidation of memories of stressful events is modulated by glucocorticoids, a type of corticosteroid hormone that is released in high levels from the adrenal glands after exposure to a stressful event. These effects occur through activation of mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs). The molecular mechanisms that underlie the effects of glucocorticoids on synaptic transmission, synaptic plasticity, learning and memory have recently begun to be identified. Glucocorticoids regulate AMPA (α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate) receptor trafficking--which is crucially involved in synaptic transmission and plasticity--both rapidly and persistently. Stress hormones may, through modulation of AMPA receptor function, promote the consolidation of behaviourally relevant information.
http://www.sciencedi...092867407012056
Cell. 2007 Oct 5;131(1):160-73.
Emotion enhances learning via norepinephrine regulation of AMPA-receptor trafficking.
Emotion enhances our ability to form vivid memories of even trivial events. Norepinephrine (NE), a neuromodulator released during emotional arousal, plays a central role in the emotional regulation of memory. However, the underlying molecular mechanism remains elusive. Toward this aim, we have examined the role of NE in contextual memory formation and in the synaptic delivery of GluR1-containing alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA)-type glutamate receptors during long-term potentiation (LTP), a candidate synaptic mechanism for learning. We found that NE, as well as emotional stress, induces phosphorylation of GluR1 at sites critical for its synaptic delivery. Phosphorylation at these sites is necessary and sufficient to lower the threshold for GluR1 synaptic incorporation during LTP. In behavioral experiments, NE can lower the threshold for memory formation in wild-type mice but not in mice carrying mutations in the GluR1 phosphorylation sites. Our results indicate that NE-driven phosphorylation of GluR1 facilitates the synaptic delivery of GluR1-containing AMPARs, lowering the threshold for LTP, thereby providing a molecular mechanism for how emotion enhances learning and memory.
http://www.ncbi.nlm....les/PMC3059607/
Front Synaptic Neurosci. 2009 Oct 13;1:2. doi: 10.3389/neuro.19.002.2009. eCollection 2009.
Hormonal regulation of AMPA receptor trafficking and memory formation.Humans and rodents retain memories for stressful events very well. The facilitated retention of these memories is normally very useful. However, in susceptible individuals a variety of pathological conditions may develop in which memories related to stressful events remain inappropriately present, such as in post-traumatic stress disorder. The memory enhancing effects of stress are mediated by hormones, such as norepinephrine and glucocorticoids which are released during stressful experiences. Here we review recently identified molecular mechanisms that underlie the effects of stress hormones on synaptic efficacy and learning and memory. We discuss AMPA receptors as major target for stress hormones and describe a model in which norepinephrine and glucocorticoids are able to strengthen and prolong different phases of stressful memories.
Edited by lostfalco, 12 August 2015 - 11:44 PM.
Posted 13 August 2015 - 03:56 AM
Thanks for your reply. Definitely, experiment and tweak it to individual needs is the best approach. I will try 10/5/10/5/10 too. Thanks for sharing your approach to better learning
No problem. =) Hope it works for you.
Posted 13 August 2015 - 02:24 PM
Hey Falco what's up? Are you still lasering (2 years and a half later) your head every other day (TULIP, PQQ, COQ10)? Or not anymore? Any news with Methylene Blue and Laser?
Thanks man, as always.
Hey, what's up Lucas? Yep, still lasering and currently combining with MB with no problems. Taking a break from PQQ and CoQ10 right now for cost reasons. I want to test MB + laser for a bit longer before I discuss it...but as I said, nothing detrimental thus far.
Also, I think it's probably a good idea for me to emphasize at this juncture that all of the various enhancement ideas I've been talking about recently pretty much presuppose that you are taking care of your mitochondria. I still think that focusing on bioenergetics should be the foundation for all other enhancements. After all, how is a synapse going to grow without the ATP required to traffic receptors and build the dendrite?
http://www.ncbi.nlm....pubmed/20797537
Neuron. 2010 Aug 26;67(4):603-17. doi: 10.1016/j.neuron.2010.07.016.
Myosin IIb regulates actin dynamics during synaptic plasticity and memory formation.
Reorganization of the actin cytoskeleton is essential for synaptic plasticity and memory formation. Presently, the mechanisms that trigger actin dynamics during these brain processes are poorly understood. In this study, we show that myosin II motor activity is downstream of LTP induction and is necessary for the emergence of specialized actin structures that stabilize an early phase of LTP. We also demonstrate that myosin II activity contributes importantly to an actin-dependent process that underlies memory consolidation. Pharmacological treatments that promote actin polymerization reversed the effects of a myosin II inhibitor on LTP and memory. We conclude that myosin II motors regulate plasticity by imparting mechanical forces onto the spine actin cytoskeleton in response to synaptic stimulation. These cytoskeletal forces trigger the emergence of actin structures that stabilize synaptic plasticity. Our studies provide a mechanical framework for understanding cytoskeletal dynamics associated with synaptic plasticity and memory formation.
http://www.ncbi.nlm....pubmed/24465547
PLoS One. 2014 Jan 22;9(1):e85367. doi: 10.1371/journal.pone.0085367. eCollection 2014.
Myosin II ATPase activity mediates the long-term potentiation-induced exodus of stable F-actin bound by drebrin A from dendritic spines.
The neuronal actin-binding protein drebrin A forms a stable structure with F-actin in dendritic spines. NMDA receptor activation causes an exodus of F-actin bound by drebrin A (DA-actin) from dendritic spines, suggesting a pivotal role for DA-actin exodus in synaptic plasticity. We quantitatively assessed the extent of DA-actin localization to spines using the spine-dendrite ratio of drebrin A in cultured hippocampal neurons, and found that (1) chemical long-term potentiation (LTP) stimulation induces rapid DA-actin exodus and subsequent DA-actin re-entry in dendritic spines, (2) Ca(2+) influx through NMDA receptors regulates the exodus and the basal accumulation of DA-actin, and (3) the DA-actin exodus is blocked by myosin II ATPase inhibitor, but is not blocked by myosin light chain kinase (MLCK) or Rho-associated kinase (ROCK) inhibitors. These results indicate that myosin II mediates the interaction between NMDA receptor activation and DA-actin exodus in LTP induction. Furthermore, myosin II seems to be activated by a rapid actin-linked mechanism rather than slow MLC phosphorylation. Thus the myosin-II mediated DA-actin exodus might be an initial event in LTP induction, triggering actin polymerization and spine enlargement.
Edited by lostfalco, 13 August 2015 - 02:35 PM.
Posted 15 August 2015 - 12:06 PM
Hey, what's up Lucas? Yep, still lasering and currently combining with MB with no problems. Taking a break from PQQ and CoQ10 right now for cost reasons. I want to test MB + laser for a bit longer before I discuss it...but as I said, nothing detrimental thus far.
Also, I think it's probably a good idea for me to emphasize at this juncture that all of the various enhancement ideas I've been talking about recently pretty much presuppose that you are taking care of your mitochondria. I still think that focusing on bioenergetics should be the foundation for all other enhancements. After all, how is a synapse going to grow without the ATP required to traffic receptors and build the dendrite?
I never could tried yet lasering with enhancers, only with creatine and dha also for cost reasons. I will try MB soon cause is cheap.
Totally agree that the take care of the mitochondria is the first step.
Thanks again!
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