Spontaneous Cannabinoid Receptor 2 (CB2) Expression in the Cochlea of Adult Albino Rat and Its Up-Regulation after Cisplatin Treatment

Abstract

We provide evidence for the presence of cannabinoid CB2 receptors in some cellular types of the cochlea of the adult albino rat. Cannabinoids and their receptors are increasingly being studied because of their high potential for clinical use. As a hyperspecialized portion of the peripheral nervous system, study of the expression and function of cannabinoid receptors in the hearing organ is of high interest. Stria vascularis and inner hair cells express CB2 receptor, as well as neurites and cell bodies of the spiral ganglion. Cellular types such as supporting cells and outer hair cells, in which the expression of other types of functional receptors has been reported, do not significantly express CB2 receptors in this study. An up-regulation of CB2 gene expression was detected after an ototoxic event such as cisplatin treatment, probably due to pro-inflammatory events triggered by the drug. That fact suggests promising potential of CB2 receptor as a therapeutic target for new treatments to palliate cisplatin-induced hearing loss and other ototoxic events which triggers inflammatory pathways.

Cnr2 is important for Ribbon Synapse Maturation and Function in Hair Cells and Photoreceptors

“…The underlying mode of action of Cnr2 in any of those cells/tissue remains to be determined. However, both groups demonstrated that Cnr2 expression was up-regulated after Cisplatin exposure [11,12]. This was strengthening an earlier claim for an anti-apoptotic role for Cnr2 in cisplatin-treated cultured cells of an auditory cells line [76].…”

“…In the inner ear, a recent report documented spontaneous Cnr2 expression in the cochlear canal of adult rats [11]. Strong immunolabelling of Cnr2 was found in the stria vascularis (SV), and maybe more surprisingly in all inner HCs (IHCs), as well as in the afferent neurites and cell bodies of spiral neurons [11]. All these localizations were confirmed independently, and additional cochlear expression was found in the spiral ligament (SL), the outer HCs (OHCs) and a subset of support cells (SCs), namely the inner and outer pillar cells (IPCs and OPCs respectively) [12].…”

“…For Cnr2, reports demonstrate the involvement in inflammation responses in the outer [74] and middle ear [75]. In the inner ear, a recent report documented spontaneous Cnr2 expression in the cochlear canal of adult rats [11]. Strong immunolabelling of Cnr2 was found in the stria vascularis (SV), and maybe more surprisingly in all inner HCs (IHCs), as well as in the afferent neurites and cell bodies of spiral neurons [11].…”

“…In sensory organs, Cnr2 expression was described in several cell types like photoreceptors of the adult retina in various mammals [9] as well as in fish [10]. More recently, Cnr2 expression was found in several cell types of the rodent inner ear like sensory hair cells (HCs) of the Organ of Corti [11,12]. However, little is known about the developmental expression pattern or the role of cnr2 in those epithelia.…”

Endocannabinoid receptor CB2R is significantly expressed in aspirin‐exacerbated respiratory disease: a pilot study

“…8 Activation of the type 2 cannabinoid receptor (CB2R) results in decreased leukotriene synthesis and leukocyte migration, as well as a reduction of T-helper 2 (Th2)-cytokine profiles. 9,10 AA is also produced by cleavage of the endocannabinoid and CB2R ligand 2-arachidonoylglycerol (2-AG) by fatty acid amid hydrolase (FAAH) or monoacylglycerol lipase (MAGL), directly increasing the production of inflammatory leukotrienes in AERD. 8,9 In this pilot study, we hypothesized that altered CB2R expression is associated with AERD and represents a novel target for future discovery.…”