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BDNF regulates neuronal sensitivity to endocannabinoids

bdnf endocannabinoids aea

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#1 Ruth

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Posted 19 June 2018 - 11:36 PM


https://www.scienced...304394009013111

The diacylglycerol lipases (DAGLα/β) synthesize 2-arachidonylglycerol (2-AG), the major endocannabinoid in the developing and adult brain (eCB). This lipid acts on cannabinoid receptors to regulate axonal growth and guidance, activity-dependent synaptic plasticity and adult neurogenesis, and can also protect neurons from excitotoxicity. 2-AG action is generally terminated by monoacylglycerol lipase (MAGL), however we know very little about the mechanisms that regulate neuronal sensitivity to eCBs. In the present study we show that the brain-derived neurotrophic factor (BDNF) can determine neuronal sensitivity to eCBs. In this context, in cultured cerebellar granule neurons (CGNs) BDNF increases the expression of CB1 receptor transcripts and decreases expression of MAGL transcripts. Using phosphorylation of Akt as the readout, we show that BDNF can promote a stable increase in neuronal sensitivity to eCBs. For example, concentrations of 2-AG and noladin either (NE) that normally do not lead to Akt phosphorylation in control neurons do so in neurons pre-treated with BDNF. In addition, Akt phosphorylation in response to a wide range of concentrations of NE was always greater in neurons pre-treated with BDNF. Our data suggests the existence of a positive feedback loop that might sustain neuronal survival in the normal brain.

https://www.scienced...27858461731000X


The shock and reminders model of PTSD resulted in depression-like symptoms.

Cannabinoid agents administered 2 h after shock exposure prevented these symptoms.

Symptoms were correlated with BDNF expression in the fear and reward circuit.

Cannabinoids may prevent and treat PTSD-depression comorbidity after severe stress.

"have shown that BDNF interacts with the eCB system in mediating neuronal survival and synaptic
plasticity (Blázquez et al., 2015; Maison et al., 2009); eg, pharmacological or genetic inhibition
of CB1 receptor down-regulated hippocampal BDNF expression (Ferreira-Vieira et al)"

https://academic.oup...1/5/485/4868137


Significance Statement

"The present research deals with the neurobiological basis of individual differences, in particular the predispositions in approach and avoidance. The findings indicated that the individual differences in the inherent predisposition to approach were associated with the basal cerebellar brain derived neurotrophic factor (BDNF) levels, and that the cerebellar BDNF levels were causally related with the acute response of approach in its double component of exploration and search for novelty. Here, we are proposing that the basal endogenous or acutely increased cerebellar BDNF levels promote explorative response and searching for novelty, components that sustain the approach pattern"

http://www.pnas.org/...2/43/15670.long

The molecular mechanisms contributing to the normal age-related decline of cognitive functions or to pathological learning and memory impairment are largely unknown. We demonstrate here that young mice (6–7 weeks) with a genetic deletion of the cannabinoid CB1 receptor performed as well as WT mice, or often better, in a number of learning and memory paradigms, including animal models of skill-learning, partner recognition, and operant conditioning. In contrast, the performance of mature mice (3–5 months) lacking CB1 receptors was much worse than that of age-matched WT animals. In most tests, these mice performed at the same level as old animals (14–17 months), suggesting that the decline in cognitive functions is accelerated in the absence of CB1 receptors. This rapid decline in CB1-deficient animals is accompanied by a loss of neurons in the CA1 and CA3 regions of the hippocampus.


https://jneuroinflam...2974-018-1059-y

Microglia function is essential to maintain the brain homeostasis. Evidence shows that aged microglia are primed and show exaggerated response to acute inflammatory challenge. Systemic inflammation signals to the brain inducing changes that impact cognitive function. However, the mechanisms involved in age-related cognitive decline associated to episodic systemic inflammation are not completely understood. The aim of this study was to identify neuropathological features associated to age-related cognitive decline in a mouse model of episodic systemic inflammation

"Early age-related cognitive impairment in mice lacking cannabinoid CB1 receptors. (full – 2005) Early age-related cognitive impairment in mice lacking cannabinoid CB1 receptors

These Cn1 (-/-) mice give us an example of a worst case scenario of a lack of functional CB1 receptors can do! They are also referred to as “knock-out” mice. Here is what happens when there are too few, or no, CB1 receptors-

Loss of Cannabinoid Receptor CB1 Induces Preterm Birth (full - 2008)Loss of Cannabinoid Receptor CB1 Induces Preterm Birth

Loss of cannabinoid receptor 1 accelerates intestinal tumor growth (full - 2008) Loss of cannabinoid receptor 1 accelerates intestinal tumor growth

Turned-Off Cannabinoid Receptor Turns On Colorectal Tumor Growth(news - 2008) Turned-off Cannabinoid Receptor Turns On Colorectal Tumor Growth

Worsening of Huntington disease phenotype in CB1 receptor knockout mice. (abst – 2011) Unbound MEDLINE | Worsening of Huntington disease phenotype in CB1 receptor knockout mice. PubMed Journal article abstract

Genes differentially expressed in CB1 knockout mice: involvement in the depressive-like phenotype. (abst – 2010) Genes differentially expressed in C... [Eur Neuropsychopharmacol. 2011] - PubMed - NCBI

Deficiency of type 1 cannabinoid receptors worsens acute heart failure induced by pressure overload in mice. (abst – 2011) Deficiency of type 1 cannabinoid receptors worse... [Eur Heart J. 2011] - PubMed - NCBI

Increased Severity of Stroke in CB1 Cannabinoid Receptor Knock-Out Mice (full - 2002) Increased Severity of Stroke in CB1 Cannabinoid Receptor Knock-Out Mice

Defective adult neurogenesis in CB1 cannabinoid receptor knockout mice. (full - 2004) Defective Adult Neurogenesis in CB1 Cannabinoid Receptor Knockout Mice

Pretty scary! So what can be done? The answer lies in this little gem of “Sci-Speak”! :D

Nutritional omega-3 deficiency abolishes endocannabinoid-mediated neuronal functions. (abst – 2011) http://www.unboundme...onal_functions_


Omega-3 fatty acids increase brain volume: while reversing many aspects of neurologic aging. (full – 2010) http://www.thefreeli......-a0237529250

#2 John250

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Posted 19 June 2018 - 11:39 PM

What’s the best omega-3 supplement available? If cost is no issue?

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#3 Ruth

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Posted 19 June 2018 - 11:40 PM

https://link.springe...-540-85081-6_28

Living systems are far from equilibrium open systems that exhibit many scales of emergent behavior. They may be abstractly viewed as a complex weave of dissipative structures that maintain organization by passing electrons from reduced hydrocarbons to oxygen. Free radicals are unavoidable byproducts of biological electron flow. Due to their highly reactive chemical properties, free radicals modify all classes of biological molecules (carbohydrates, lipids, nucleic acids, and proteins). As a result, free radicals are destructive. The generally disruptive nature of free radicals makes them the “friction of life.” As such, they are believed to be the etiological agents behind age related illnesses such as cardiovascular, immunological, and neurological diseases, cancer, and ageing itself. Free radicals also play a critical constructive role in living systems. From a thermodynamic perspective, life can only exist if a living system takes in sufficient negative entropy from its environment to overcome the obligatory increase in entropy that would result if the system could not appropriately exchange mass, energy and information with its environment. Free radicals are generated in response to perturbations in the relationship between a living system and its environment. However, evolution has selected for biological response systems to free radicals so that the cellular biochemistry can adapt to environmental perturbations by modifying cellular gene expression and biochemistry. Endocannabinoids are marijuana-like compounds that have their origins hundreds of millions of years in the evolutionary past. They serve as fundamental modulators of energy homeostasis in all vertebrates. Their widespread biological activities may often be attributed to their ability to minimize the negative consequences of free radicals.

#4 Ruth

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Posted 20 June 2018 - 12:41 AM

Well fish itself, algae-based, or if at least has verified-omegas...than many combinations of supplements for increased amounts of bio-availability, so basically different amounts of different supplements brands/strengths(same difference)

#5 Oakman

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Posted 20 June 2018 - 01:10 PM

Well fish itself, algae-based, or if at least has verified-omegas...than many combinations of supplements for increased amounts of bio-availability, so basically different amounts of different supplements brands/strengths(same difference)

 

Well, for example, what do you take to facilitate these functions you're discussing?



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#6 Ruth

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Posted 20 June 2018 - 02:35 PM

Like corporate supplements?





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