Abstract
The astrocytes have gained in recent decades an enormous interest as a potential target for neurotherapies, due to their essential and pleiotropic roles in brain physiology and pathology. Their precise regulation is still far from understood, although several candidate molecules/systems arise as promising targets for astrocyte-mediated neuroregulation and/or neuroprotection. The cannabinoid system and its ligands have been shown to interact and affect activities of astrocytes. Cannabidiol (CBD) is the main non-psychotomimetic cannabinoid derived from Cannabis. CBD is devoid of direct CB1 and CB2 receptor activity, but exerts a number of important effects in the brain. Here, we attempt to sum up the current findings on the effects of CBD on astrocyte activity, and in this way on central nervous system (CNS) functions, across various tested models and neuropathologies. The collected data shows that increased astrocyte activity is suppressed in the presence of CBD in models of ischemia, Alzheimer-like and Multiple-Sclerosis-like neurodegenerations, sciatic nerve injury, epilepsy, and schizophrenia. Moreover, CBD has been shown to decrease proinflammatory functions and signaling in astrocytes.
Highlights
Astrocytes are the most numerous cells populating the central nervous system (CNS)
CBD injections into the injured mice resulted in a significant rescue of dorsal root ganglia (DRG) neurons, spinal motoneurons, and pre-synaptic terminals, which was coupled with a reduction of neuronal apoptosis and of astrogliosis
Campos and co-authors [107] showed that the anxiolytic effect of CBD in mice subjected to chronic unpredictable stress was accompanied by increases in hippocampal neurogenesis as tracked using
Summary
Astrocytes are the most numerous cells populating the central nervous system (CNS). Research during the last two decades has shown that they actively participate in brain development and activity, and maintain tissue homeostasis, far beyond their previously believed role of a sole “glue”-like support for neurons. Following their activation, the astrocytes secrete chemokines, cytokines, neurotoxic factors, molecules affecting blood vessel diameter ( modulating blood flow), such as nitric oxide and prostaglandins, and by this way affect BBB permeability. The astrocytes secrete chemokines, cytokines, neurotoxic factors, molecules affecting blood vessel diameter ( modulating blood flow), such as nitric oxide and prostaglandins, and by this way affect BBB permeability Due to their crucial involvement in brain function, astrocytes have gained robust interest as a potential target for neurotherapies. Mounting evidence shows that many cannabinoids, including phytocannabinoids (constituents of the Cannabis plant), endocannabinoids, and synthetic ligands, can modulate the intensity of reactive gliosis, resulting in neuromodulatory, anti-inflammatory, and neuroprotective effects in both mature and immature brain [7,8,9,10]. Our aim in this manuscript is to summarize the findings on the effects of CBD on astrocytes in various experimental models of brain insults and pathologies
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