Expression And Distribution Of ErbB4 And CB1R In Monkey Prefrontal Cortex

Part I: Expression and Distribution of ErbB4 in Monkey Prefrontal CortexErbB4 and its ligand NRG1 are two well-known susceptibility genes of schizophrenia.ErbB4 is widely distributed and involved in many physiological processes,such as neurogenesis,synaptic plasticity,neuronal migration,synaptic formation,and regulation of neurotransmission.Clinical studies have shown that cognitive manifestations of schizophrenia is of lower working memory ability.In mice,blockade of ErbB4 in the prefrontal cortex leads to severe impairment of working memory,providing experimental evidence that loss function of NRG1/ErbB4 signaling in the prefrontal cortex may lead to schizophrenia.By constructing Er Bb4-reporter mice,previous studies have shown that Er Bb4 is highly expressed in GABAergic interneurons in the cerebral cortex,especially in PV-positive cells,suggesting that PV-positive cells may be the main target of NRG1/Er Bb4 signaling in the brain.However,the previous studies were all carried out in rodents and their brains differ very much from primate’s brains in terms of structures and functions.The present study aimed to investigate whether and how ErbB4 is expressed and distributed in the PFC of non-human primate.The expression and distribution of ErbB4 in the PFC of rhesus monkeys was determined by using western blot and immunofluorescence staining.The results showed that:1)ErbB4 was highly expressed in the monkey prefrontal cortex;2)ErbB4 was expressed differently in subareas of the prefrontal cortex,with the most abundant expression in area 46;3)ErbB4 was distributed in laminar-dependent pattern,with highest expression in layer Ⅳ.Both the fluorescence density and the number of cells in layer Ⅳ were the largest among all the prefrontal cortical layers.ErbB4 demonstrated an inverted "U" pattern of distribution,with an increase in layers Ⅱ-Ⅳ and a decrease in layers Ⅳ-Ⅵ;4)ErbB4 was highly co-expressed in PV-positive interneurons in area 46.The present work provides experimental evidence that NRG1/ErbB4 signaling may be involved in regulating prefrontal cortical cognitive functions in nonhuman primates,and provides insights for the development of drug targets for schizophrenia.Part II: Expression and Distribution of CB1 R in Monkey Prefrontal CortexCannabis is one of the first plants to be identified as having addictive properties.China is believed to be the earliest country to grow and use cannabis,dating back 3,400 years.Marijuana has long been used to treat mental illness.However,its abuse can cause many side effects.The main active ingredients of cannabis have three main categories: plant cannabinoids,endocannabinoids,and synthetic cannabinoids.The endocannabinoid system exists and participates in regulating various physiological functions in animals,and this system contains endocannabinoids and cannabinoid receptors.Cannabinoid receptor 1(CB1R)and cannabinoid receptor 2(CB2R)are currently identified and classified in humans.CB1 R mainly exists in the central nervous system,while CB2 R mainly in the peripheral system.The signaling pathways mediated by the two subtypes of receptors are associated with many diseases.The prefrontal cortex is considered as the central brain area for higher cognitive functions.It is known that CB1 R is expressed in the PFC of mice.The rodent brain differs greatly from the primate brain in structures and functions.It is necessary to know whether and how CB1 R is expressed and distributed in the prefrontal cortex of primates.In the present study,we investigated the expression and distribution of CB1 R in the prefrontal cortex of rhesus monkeys using western blot and immunofluorescence staining.Our results showed that: 1)CB1R was highly expressed in the monkey prefrontal cortex;2)CB1R had different expression in different subregions of the prefrontal cortex,with relatively abundant expression in area 46;and 3)CB1R was co-expressed in PV-positive interneurons in area 46.The present study provides an important morphological basis for understanding the regulation mechanism of prefrontal cortical CB1 R in cognitive functions.