Microglial cannabinoid receptor type 1 mediates social memory deficits in mice produced by adolescent THC exposure and 16p11.2 duplication.
Yuto HasegawaJuhyun KimGianluca UrsiniYan JouroukhinXiaolei ZhuYu MiyaharaFeiyi XiongSamskruthi MadireddyMizuho ObayashiBeat LutzAkira SawaSolange P BrownMikhail V PletnikovAtsushi KamiyaPublished in: Nature communications (2023)
Adolescent cannabis use increases the risk for cognitive impairments and psychiatric disorders. Cannabinoid receptor type 1 (Cnr1) is expressed not only in neurons and astrocytes, but also in microglia, which shape synaptic connections during adolescence. However, the role of microglia in mediating the adverse cognitive effects of delta-9-tetrahydrocannabinol (THC), the principal psychoactive constituent of cannabis, is not fully understood. Here, we report that in mice, adolescent THC exposure produces microglial apoptosis in the medial prefrontal cortex (mPFC), which was exacerbated in a model of 16p11.2 duplication, a representative copy number variation (CNV) risk factor for psychiatric disorders. These effects are mediated by microglial Cnr1, leading to reduction in the excitability of mPFC pyramidal-tract neurons and deficits in social memory in adulthood. Our findings suggest the microglial Cnr1 may contribute to adverse effect of cannabis exposure in genetically vulnerable individuals.
Keyphrases
- inflammatory response
- neuropathic pain
- mental health
- copy number
- prefrontal cortex
- lipopolysaccharide induced
- young adults
- lps induced
- spinal cord
- mitochondrial dna
- traumatic brain injury
- healthcare
- depressive symptoms
- spinal cord injury
- oxidative stress
- working memory
- high fat diet induced
- genome wide
- cell death
- dna methylation
- type diabetes
- emergency department
- endoplasmic reticulum stress
- gene expression
- binding protein
- signaling pathway
- skeletal muscle
- cell cycle arrest
- adverse drug
- cell proliferation