A major challenge in neuroscience lies in understanding how molecular and circuit differences in the brain synergistically contribute to sex differences in behavioral phenotypes. Sex differences in the brain may arise from the identity, distribution and relative abundance of cell types.  

The cannabinoid 1 receptor (CB₁R), the main receptor for cannabinoids and endocannabinoids (eCB), is the most abundantly expressed G-protein-coupled receptor in the brain and is highly conserved in animal evolution. However, whole-brain mapping of CB₁R expression in adult male and female mice has not yet been described in detail. 

Recently, a research team focusing on the neural functions of the endocannabinoid system led by Dr. WANG Feng, from Brain Cognition and Brain Disease Institute of Shenzhen Institute of Advanced Technology at Chinese Academy of Sciences, demonstrated that CB₁R mRNA expression displays a sexual dimorphic pattern in several regions in the adult mouse brain.  

According to the current study published on the JOURNAL OF COMPARATIVE NEUROLOGY in January 2020, a systemic mapping of CB₁R mRNA expression was conducted and compared for the first time in the male and female adult C57BL/6J mouse (a common inbred strain of laboratory mouse) brain.  

This study found that the neocortex, medial habenula, striatum, hippocampus and cerebellum are enriched with CB₁R mRNA signals. In the orbital cortex, insular cortex, cingulate cortex, piriform cortex, secondary visual cortex, caudate putamen and ventral hippocampus CA1, there were significantly more CB₁R positive cells in males than in females. In the fornix and dorsal hypothalamus, CB₁R positive cells displayed more in females on the contrary. It is plausible that CB₁R expression difference in the brain contributes to sex differences in various phenotypes. For example, the striatum, which harbors greater amount of CB₁R positive cells in males, has been widely recognized as the main affected region in Parkinson’s disease with a higher incidence in males. The dorsal hypothalamus with a female-biased number of CB₁R positive cells is associated with maternal behaviors.  

More interestingly, CB₁R mRNA seems to fluctuate along estrous cycle in female brain regions, including the medial amygdala, basolateral amygdala and parabrachial nucleus, which has not been reported before.  

This study maps, for the first time, the localization of CB1R positive cells on a whole‐brain scale in both genders, these findings provide a basis for understanding sexual dimorphism in physiological and pathological brain functions related to cannabinoids and endocannabinoids. 

Figure. Brain regions that show sex difference in CB₁R positive cells. (Image by Prof. WANG)

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ZHANG Xiaomin

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