8 replies to this topic

[Valor5]

So according to Hellweg R in his paper,

Serum concentrations of nerve growth factor and brain-derived neurotrophic factor in depressed patients before and after antidepressant treatment.

Paroxetine at 40mg given to depressed patients decreased their bdnf by 12%. So the scary thing to me is the fact that these people lie to consumers because of the apparent contradictions...it's scary who can you trust?

[Turnbuckle]

First of all, you can't trust the pharmaceutical industry. They lie up a storm to sell their products . But did they (or anyone else) tell you that paroxetine would increase BDNF? 

[Major Legend]

I'm not surprised, the side effects of SSRIs are well documented. Arguably, people would rather have an impaired brain or sexual drive than be depressed.

[Valor5]

First of all, you can't trust the pharmaceutical industry. They lie up a storm to sell their products . But did they (or anyone else) tell you that paroxetine would increase BDNF?

Yes, it is understood that BDNF is what is bringing "relief" through these drugs, along with the inhibition of reuptake. But what concerns me is that, well this finding was found in humans and the others in mice, but there are contradictions out there and I am not sure what is true. Many people don't seem to find real relief from antidepressants so why the emphasis on BDNF, is it a selling point? A reduction in BDNF for a depressed person is a very serious concern.

[Valor5]

I'm not surprised, the side effects of SSRIs are well documented. Arguably, people would rather have an impaired brain or sexual drive than be depressed.

My view is people follow others like doctors and such with a childlike faith...people have been poisoned with mercury by so called doctors so I feel like someone is laughing, smiling I suppose all the way to the bank but this is conjecture and well there must be a better way than following old ways of living and expecting so called doctors with your life to make it better. May the force be with us because I feel we are in serious trouble. But perhaps I am being overly dramatic, but it's not the case with many broken desperate people. It's just that unless I understand and measure the BDNF I guess I won't be satisfied. I have faith in natural things, they seem to do the least damage although I must say mercury is natural but naturally really bad so we really need all the marketing and lying and buying and selling mentallity I guess out of the picture.

[Turnbuckle]

Yes, it is understood that BDNF is what is bringing "relief" through these drugs, along with the inhibition of reuptake. But what concerns me is that, well this finding was found in humans and the others in mice, but there are contradictions out there and I am not sure what is true. Many people don't seem to find real relief from antidepressants so why the emphasis on BDNF, is it a selling point? A reduction in BDNF for a depressed person is a very serious concern.

 

Paroxetine inhibits the reuptake of serotonin. Any effect on BDNF would be secondary. And if you look at papers about paroxetine and BDNF, they are with mice, or in vitro, or in small groups of humans with statistics that are borderline. In fact, it is not uncommon to find papers with apparently opposite conclusions, and esp. with something like this, where the effect is small to begin with.

 

I'm still wondering who is pushing the BDNF aspect. Is it the manufacturer? Or random people on the internet?

[Valor5]

Paroxetine inhibits the reuptake of serotonin. Any effect on BDNF would be secondary. And if you look at papers about paroxetine and BDNF, they are with mice, or in vitro, or in small groups of humans with statistics that are borderline. In fact, it is not uncommon to find papers with apparently opposite conclusions, and esp. with something like this, where the effect is small to begin with.

I'm still wondering who is pushing the BDNF aspect. Is it the manufacturer? Or random people on the internet?

Well to add to the complexity. My understanding is that agonism of 5ht1a and or 5ht2a leads to and is essential for learning. And paroxetine to my knowledge according to the affinity chart on Wikipedia is agonist at those receptors. Now my concern or interest would be what role BDNF plays in learning, and it does. Paroxetine is anticholinergic and I think this may explain the BDNF dilemma.

"More recent studies also
support the notion that circulating BDNF is a biomarker of
memory and general cognitive function in healthy adults
(Komulainen et al. 2008; Gunstad et al. 2008)."
To answer your last question I saw an excerpt I think from pubmed a paper that came from Novartis Symposium.

This is a little disorganized I am just out of time right now. But if anyone is interested I will try to expand more. Thank you.

[Ruth]

Curcumin?
melatonin?
https://www.nature.c...1380-018-0061-1
The diurnal regulation of dopamine is important for normal physiology and diseases such as addiction. Here we find a novel role for the CLOCK protein to antagonize CREB-mediated transcriptional activity at the tyrosine hydroxylase (TH) promoter, which is mediated by the interaction with the metabolic sensing protein, Sirtuin 1 (SIRT1). Additionally, we demonstrate that the transcriptional activity of TH is modulated by the cellular redox state, and daily rhythms of redox balance in the ventral tegmental area (VTA), along with TH transcription, are highly disrupted following chronic cocaine administration. Furthermore, CLOCK and SIRT1 are important for regulating cocaine reward and dopaminergic (DAergic) activity, with interesting differences depending on whether DAergic activity is in a heightened state and if there is a functional CLOCK protein. Taken together, we find that rhythms in cellular metabolism and circadian proteins work together to regulate dopamine synthesis and the reward value for drugs of abuse

The Neuroprotective Effects of Flaxseed Oil Supplementation on Functional Motor Recovery in a Model of Ischemic Brain Stroke: Upregulation of BDNF and GDNF
Cerebral ischemic stroke is a common leading cause of disability. Flaxseed is a richest plant-based source of antioxidants. In this study, the effects of flaxseed oil (FSO) pretreatment on functional motor recovery and gene expression and protein content of neurotrophic factors in motor cortex area in rat model of brain ischemia/reperfusion (I/R) were assessed. Transient middle cerebral artery occlusion (tMCAo) in rats was used as model brain I/R. Rats (6 in each group) were randomly divided into four groups of Control (Co+normal saline [NS]), Sham (Sh+NS), tMCAo+NS and tMCAo+FSO. After three weeks of pretreatment with vehicle or FSO (0.2 ml~800 mg/kg body weight), the rats were operated in sham and ischemic groups. Ischemia was induced for 1 h and then reperfused. After 24 h of reperfusion, neurological examination was performed, and animals were sacrificed, and their brains were used for molecular and histopathological studies. FSO significantly improved the functional motor recovery compared with tMCAo+NS group (P<0.05). A significant reduction in brain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor (GDNF) mRNAs and protein levels were observed in the tMCAo+NS group compared with Co+NS and Sh+NS group (P<0.05). A significant increase of BDNF and GDNF mRNAs and proteins was recorded in the tMCAo+FSO group compared with Co+NS, Sh+NS and tMCAO+NS groups (P<0.05). The results of the current study demonstrated that pretreatment with FSO had neuroprotective effects on motor cortex area following cerebral ischemic stroke by increasing the neurotrophic factors (BDNF, GDNF). ©

Edited by Ruth, 24 July 2018 - 09:44 PM.

[Valor5]

Curcumin?
melatonin?
https://www.nature.c...1380-018-0061-1
The diurnal regulation of dopamine is important for normal physiology and diseases such as addiction. Here we find a novel role for the CLOCK protein to antagonize CREB-mediated transcriptional activity at the tyrosine hydroxylase (TH) promoter, which is mediated by the interaction with the metabolic sensing protein, Sirtuin 1 (SIRT1). Additionally, we demonstrate that the transcriptional activity of TH is modulated by the cellular redox state, and daily rhythms of redox balance in the ventral tegmental area (VTA), along with TH transcription, are highly disrupted following chronic cocaine administration. Furthermore, CLOCK and SIRT1 are important for regulating cocaine reward and dopaminergic (DAergic) activity, with interesting differences depending on whether DAergic activity is in a heightened state and if there is a functional CLOCK protein. Taken together, we find that rhythms in cellular metabolism and circadian proteins work together to regulate dopamine synthesis and the reward value for drugs of abuse

The Neuroprotective Effects of Flaxseed Oil Supplementation on Functional Motor Recovery in a Model of Ischemic Brain Stroke: Upregulation of BDNF and GDNF
Cerebral ischemic stroke is a common leading cause of disability. Flaxseed is a richest plant-based source of antioxidants. In this study, the effects of flaxseed oil (FSO) pretreatment on functional motor recovery and gene expression and protein content of neurotrophic factors in motor cortex area in rat model of brain ischemia/reperfusion (I/R) were assessed. Transient middle cerebral artery occlusion (tMCAo) in rats was used as model brain I/R. Rats (6 in each group) were randomly divided into four groups of Control (Co+normal saline [NS]), Sham (Sh+NS), tMCAo+NS and tMCAo+FSO. After three weeks of pretreatment with vehicle or FSO (0.2 ml~800 mg/kg body weight), the rats were operated in sham and ischemic groups. Ischemia was induced for 1 h and then reperfused. After 24 h of reperfusion, neurological examination was performed, and animals were sacrificed, and their brains were used for molecular and histopathological studies. FSO significantly improved the functional motor recovery compared with tMCAo+NS group (P<0.05). A significant reduction in brain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor (GDNF) mRNAs and protein levels were observed in the tMCAo+NS group compared with Co+NS and Sh+NS group (P<0.05). A significant increase of BDNF and GDNF mRNAs and proteins was recorded in the tMCAo+FSO group compared with Co+NS, Sh+NS and tMCAO+NS groups (P<0.05). The results of the current study demonstrated that pretreatment with FSO had neuroprotective effects on motor cortex area following cerebral ischemic stroke by increasing the neurotrophic factors (BDNF, GDNF). ©

Thanks for sharing that Ruth. About cocaine and flaxseed. Seems like good sleep is very important. I'll have too look more into that.

In one of the quotes above paper and another it was found that paroxetine had similar effects on healthy adults that would happen in people with frontotemporal variant dementia when subjected to the elimination of tryptophan from the diet. Also paroxetine made things worse in this group as well as a schizophrenic group. So paroxetine is a looser in my book. It is doing something bad to the brain not sure what. So...

"Paroxetine does not improve symptoms and impairs cognition
in frontotemporal dementia: a double-blind randomized controlled trial"

"Low BDNF is associated with cognitive impairment
in chronic patients with schizophrenia"