The Neurobiology of the Endocannabinoid System and Brain Plasticity (Lutz, 2020)

Описание: This video explores the innate cannabinoid system in the human brain & body, using Lutz' 2020 review as our guide.

I. Cannabis, Cannabinoids, & the Endocannabinoid System
Cannabis: Plant with psychedelic properties that yields marijuana.
Marijuana: Dried cannabis plant material.
THC & CBD: Cannaibnoids (active ingredients in marijuana).
Endogenous: Produced and/or exists internally (in the body &/or brain).
Endocannabinoid: Endogenous cannabinoids.
Cannabinoid molecules that act like THC & CBD...
But/and are synthesized and exist endogenously, in the brain and body.

II. The Endocannabinoid System (ECS)
The ECS is a highly versatile signaling system in the nervous system.
It is evolutionarily well conserved in vertebrates.
The system regulates many biological processes to maintain homeostasis.
Major components include the CB1 and CB2 cannabinoid receptors.
These are G protein-coupled receptors involved in signal transduction.
The system uses ligands called endocannabinoids like anandamide.
Another key ligand is 2-arachidonoylglycerol, or 2-AG.
These ligands are derivatives of the fatty acid arachidonic acid.
The ECS is integrated into broad functional networks in the body.

III. Receptor Expression And Localization
CB1 receptors are found in virtually all brain regions.
They are present in neurons, astrocytes, and microglia cells.
High levels of CB1 mRNA are found in GABAergic interneurons.
Glutamatergic neurons generally contain lower levels of CB1.
The dominant site of CB1 proteins is the presynaptic terminal.
CB1 activation suppresses presynaptic neurotransmitter release.
Functional CB1 receptors are also found in mitochondria.
CB2 receptors are found in peripheral and brain-resident immune cells.
CB2 expression is upregulated in response to chronic pain and stroke.

IV. Synaptic Plasticity And Signaling
The ECS fine-tunes physiological processes to keep homeostatic set-points.
2-AG travels retrogradely from postsynaptic to presynaptic sites.
This signaling reduces calcium influx at the presynaptic terminal.
This leads to depolarization-induced suppression of excitation.
It also mediates depolarization-induced suppression of inhibition.
CB1 receptor signaling depends on the specific cellular context.
Receptors can form homo- and heterodimers to integrate signals.
CB1 receptors are typically coupled to Gi/o proteins.
This coupling inhibits N- and P/Q-type calcium channels.

V. Cellular Plasticity And Neurogenesis
The ECS regulates the generation of new neurons in the adult brain.
Major neurogenesis sites include the hippocampus and lateral ventricle.
Proliferation of neural stem cells is tightly regulated by the ECS.
Blocking CB1 receptors can blunt exercise-induced neurogenesis.
2-AG signaling is required for maintaining cell proliferation.
Cannabidiol may enhance neurogenesis by facilitating ECS signaling.
The ECS helps replenish oligodendrocytes for myelin repair.
CB1 deficiency in stem cells reduces dendritic branching.

VI. Dysregulation And Therapeutic Potential
Dysregulated ECS activity is linked to neuropsychiatric disorders.
Chronic stress and metabolic factors can disrupt ECS balance.
Genetic polymorphisms in FAAH are linked to anxiety and depression.
Pharmacological interventions aim to restore homeostatic set-points.
Strategies include inhibiting enzymes like FAAH and MAGL.
Peripheral CB1 antagonists are being developed to avoid CNS side effects.
Allosteric modulators offer a promising alternative to direct agonists.
Understanding the ECS aids the design of better therapeutic drugs.

#neuroscience #endocannabinoidsystem #brainplasticity #neurobiology #CB1receptor #mentalhealth #synapticplasticity #neurogenesis #medicalresearch #brainscience

Lutz, B. (2020). Neurobiology of cannabinoid receptor signaling. Dialogues in Clinical Neuroscience, 22 (3), 207-222. https://doi.org/10.31887/DCNS.2020.22...

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