Spatial distribution of cannabinoid receptor type 1 (CB1) in normal canine central and peripheral nervous system

Abstract

The endocannabinoid system is a regulatory pathway consisting of two main types of cannabinoid receptors (CB1 and CB2) and their endogenous ligands, the endocannabinoids. The CB1 receptor is highly expressed in the central and peripheral nervous systems (PNS) in mammalians and is involved in neuromodulatory functions. Since endocannabinoids were shown to be elevated in cerebrospinal fluid of epileptic dogs, knowledge about the species specific CB receptor expression in the nervous system is required. Therefore, we assessed the spatial distribution of CB1 receptors in the normal canine CNS and PNS. Immunohistochemistry of several regions of the brain, spinal cord and peripheral nerves from a healthy four-week-old puppy, three six-month-old dogs, and one ten-year-old dog revealed strong dot-like immunoreactivity in the neuropil of the cerebral cortex, Cornu Ammonis (CA) and dentate gyrus of the hippocampus, midbrain, cerebellum, medulla oblongata and grey matter of the spinal cord. Dense CB1 expression was found in fibres of the globus pallidus and substantia nigra surrounding immunonegative neurons. Astrocytes were constantly positive in all examined regions. CB1 labelled neurons and satellite cells of the dorsal root ganglia, and myelinating Schwann cells in the PNS. These results demonstrate for the first time the spatial distribution of CB1 receptors in the healthy canine CNS and PNS. These results can be used as a basis for further studies aiming to elucidate the physiological consequences of this particular anatomical and cellular distribution.

miR‑1273g‑3p promotes proliferation, migration and invasion of LoVo cells via cannabinoid receptor 1 through activation of ERBB4/PIK3R3/mTOR/S6K2 signaling pathway

“…CNR1, the gene encoding cannabinoid receptors 1 (CB1), is highly expressed in the central and peripheral nervous systems (PNS) in mammalians and is involved in neuromodulatory functions (21). CNR1 expression outside the brain has been associated with cell migration and tumor growth (12). Previous studies demonstrated that CNR1 may provide a therapeutic target in tumor intervention and its anti-tumor actions by proliferation arrest or induction of apoptosis, suppression of angiogenesis and tumor metastatic spreading (18,22).…”

“…Cannabinoid receptor 1 (CNR1), the gene encoding cannabinoid receptors (CB1), a member of the endocannabinoid system, is highly expressed in the central and peripheral nervous systems (PNS) in mammalians (11,12). CNR1 expression outside the brain has been associated with cell migration and tumor procession (1).…”

Pharmacokinetics of Sativex® in Dogs: Towards a Potential Cannabinoid-Based Therapy for Canine Disorders

“…It is also important to remark that most elements of the endocannabinoid system have been found in canine tissues and cells with functions, in general, equivalent to humans. For example, the CB 1 receptors are highly expressed in both central and peripheral nervous system in dogs playing similar neuromodulatory functions and with a spatial distribution that mostly overlaps the one found in humans [28]. This cross-species similarity is also apparent for CB 2 receptor and fatty acid amide hydrolase (FAAH), and other indirect endocannabinoid-related components, including GPR55, peroxisome proliferator-activated receptors (PPAR) and transient receptor potential vanilloid type-1 (TRPV 1 ) [29,30].…”

Cannabis, One Health, and Veterinary Medicine: Cannabinoids’ Role in Public Health, Food Safety, and Translational Medicine

“…Salzet and colleagues noted that the "Cannabinoid system in all probability originated in 'simple' and primitive animals to control physio pathological responses, either similar or entirely different from those that are modulated by endocannabinoids in higher vertebrates and mammals" 161 and that "Anandamide, by acting at CB1-like receptors, seems to induce often similar responses in both mammalian and invertebrate cells, particularly for what concerns the modulation of neurotransmitter release and action and the control of immune cell function [emphasis added]." 171 Differences of cannabinoid receptors' density and distribution in animals [172][173][174] can account for therapeutic effects in animal models that do not translate well into human models.…”