Endocannabinoids in synaptic plasticity and neuroprotection.

Area of Science:

• Neuroscience
• Molecular Biology
• Pharmacology

Background:

• Endocannabinoids (eCBs) are endogenous lipid mediators influencing numerous physiological and pathological processes.
• While typically inhibitory via CB1 receptors, eCB signaling can also facilitate excitatory synaptic transmission in the brain.

Purpose of the Study:

• To review the multifaceted roles of eCB signaling in synaptic plasticity and neuroprotection.
• To highlight the mechanisms underlying eCB-mediated potentiation of excitatory transmission and its role in brain homeostasis.

Main Methods:

• Review of recent studies on eCB signaling in the hippocampus.
• Analysis of molecular mechanisms involving 2-arachidonoylglycerol (2-AG), NMDA receptors, mGluRs, Ca(2+) influx, and PPAR-γ.

Main Results:

• Spatiotemporally primed inputs induce long-lasting potentiation of excitatory transmission at Schaffer collateral (SC)-CA1 synapses.
• This potentiation is mediated by 2-AG signaling, involving postsynaptic receptors and intracellular Ca(2+).
• 2-AG also exerts anti-inflammatory and neuroprotective effects through receptor-dependent and -independent pathways.

Conclusions:

• eCB signaling, especially via 2-AG, plays a more significant role in maintaining brain function and integrity than previously understood.
• 2-AG signaling contributes to neuroprotection and resolution of neuroinflammation, partly through peroxisome proliferator-activated receptor-γ activation.