Cognitive improvement via cortical cannabinoid receptors and choline-containing lipids.

Background And Purpose: Recent research linking choline-containing lipids to degeneration of basal forebrain cholinergic neurons in neuropathological states illustrates the challenge of balancing lipid integrity with optimal acetylcholine levels, essential for memory preservation. The endocannabinoid system influences learning and memory processes regulated by cholinergic neurotransmission. Therefore, we hypothesised that activation of the endocannabinoid system may confer neuroprotection against cholinergic degeneration.

Cannabinoid signaling modulation through JZL184 restores key phenotypes of a mouse model for Williams-Beuren syndrome.

Williams-Beuren syndrome (WBS) is a rare genetic multisystemic disorder characterized by mild-to-moderate intellectual disability and hypersocial phenotype, while the most life-threatening features are cardiovascular abnormalities. Nowadays, there are no pharmacological treatments to directly ameliorate the main traits of WBS. The endocannabinoid system (ECS), given its relevance for both cognitive and cardiovascular function, could be a potential druggable target in this syndrome.

Cannabinoid Receptors and Glial Response Following a Basal Forebrain Cholinergic Lesion.

The endocannabinoid system modulates learning, memory, and neuroinflammatory processes, playing a key role in neurodegeneration, including Alzheimer's disease (AD). Previous results in a rat lesion model of AD showed modulation of endocannabinoid receptor activity in the basalo-cortical pathway following a specific lesion of basal forebrain cholinergic neurons (BFCNs), indicating that the glial neuroinflammatory response accompanying the lesion is related to endocannabinoid signaling. In this study, 7 days after the lesion, decreased astrocyte and increased microglia immunoreactivities (GFAP and Iba-1) were observed, indicating microglia-mediated neuroinflammation.

Handling and novel object recognition modulate fear response and endocannabinoid signaling in nucleus basalis magnocellularis.

Storage of aversive memories is of utmost importance for survival, allowing animals to avoid upcoming similar stimuli. However, without reinforcement, the learned avoidance response gradually decreases over time. Although the molecular mechanisms controlling this extinction process are not well known, there is evidence that the endocannabinoid system plays a key role through CB receptor-mediated modulation of cholinergic signaling.