| Empathy refers to that one can experience what others are going through,feel others’ emotions and respond to it.As a prosocial behavior,empathy is evolutionarily conservative and it is widespread from birds and rodents to primate animals.Empathy not only plays a crucial role in the survival and reproduction of animals,but also shows a key role in promoting the social development and the formation of good personal relationships in human society.High empathy promotes the formation of mutual help behaviors and altruism,while low empathy will lead to apathy,crimes and other anti-social behaviors,which is not conducive to the harmonious development of the society.Therefore,it is essential to study the mechanism of empathic behavior for promoting the harmonious development of the society and preventing from related mental diseases.Empathy consists of two parts in function,which are emotional empathy and cognitive empathy.Emotional empathy refers to that individuals can feel and experience what others are going through.Cognitive empathy refers to that individuals can understand the goals and the viewpoints of others,feeling others’ emotional states meanwhile.Empathy can be divided into three levels which is made up of emotional contagion,consolation and goal helping.Emotional contagion and consolation focus on emotional empathy,while goal helping focuses on cognitive empathy.Emotional empathy is widespread in lower and higher animals while cognitive empathy mainly exists in humans.Rodents often exhibits emotional contagion and consolation,which means mice are often freezing when observing its companion suffering from electric shock and comforting its companion after stress.At present,the mechanism of these behaviors is not well understood.Studies have found that testosterone can promote aggressive behavior and inhibit parental behavior.Vasopressin(AVP)promotes aggression,and testosterone promotes the synthesis of AVP and it is considered that empathic behavior is derived from parental behavior,so we hypothesized that testosterone might affect empathic behavior,and there is a downstream pathway that affects empathic behavior by promoting the synthesis and secretion of AVP.PVN is the key region for AVP secretion,and the anterior cingulate gyrus(ACC)is an important brain region for regulation of empathic behavior.Whether they are sensitive to changes in testosterone content and thus affect individual empathic behavior is unknown.1.Species and sexual differences in social and empathic behavior between monogamous mandarin voles and C57 miceA total of 30 adult monogamous mandarin voles and C57 mice were elected,dividing into four groups: male monogamous mandarin vole group,female monogamous mandarin vole group,male C57 mice group female C57 group.The results showed that the sociality of male monogamous mandarin vole group was significantly higher than that of male C57 mice group while there was no significant difference between female monogamous mandarin vole group and female C57 mice group.C57 mice showed significant difference in gender in empathy behavior(gnawing,neglecting and freezing),while monogamous mandarin voles showed no significant difference in gender in empathy behavior.Since female voles showed more aggressive behavior than male voles,and male mice in C57 showed more aggressive behavior than female mice,we speculated that the difference in empathy level between male and female mice was caused by the difference of testosterone level between males and females.Therefore,the following studies mainly selected C57 mice as animal models.2.Effects of testosterone reduction induced by castration on sociability and empathy in C57 miceC57 mice of 6 weeks were divided into control group and castration group which were respectively under sham surgery and castration surgery.After a week of restoring from surgery,they were established a relationship with one other mice.In the third week,the control group and castration group were tested for open field test,elevated plus maze test,emotional contagion test and consolation test.Results show that serum testosterone level decreased significantly after castration according to Elisa and the duration of emotional contagion and consolation is significantly increased in castration group compared with control group.3.Effects of reduced testosterone induced by castration on AVP system in C57miceThe relative expression of AVP m RNA and protein of AVP and V1 a R and the numbers of AVP-ir cells in PVN,ACC and Hip of C57 mice were detected by q PCR WB and IF assay,respectively.The experimental results showed that the relative expression of AVP m RNA in PVN and ACC of castration surgery group was significantly decreased and the relative density of AVP protein and V1 a R protein was significantly decreased compared with sham surgery group.The results suggested that reduction of testosterone can significantly reduce the expression of AVP and its receptor V1 a R in ACC and PVN,accompanied by a significant increase in empathic behavior.4.Effects of exogenous injection of testosterone propionate and V1 a R antagonist on empathy behavior in C57 miceMale castrated C57 mice were injected with testosterone propionate(TP)alone or testosterone propionate combined with V1 a Rantagonist(TP+A)in ACC.The results suggested that male castrated C57 mice injected with testosterone propionate(TP)alone had significantly reduced ability of emotional contagion and consolation,compared with the control group.Compared with male C57 mice injected with testosterone propionate(TP)alone,the ability of emotional contagion and consolation of male castrated C57 mice injected with V1 a R antagonist(TP+A)were significantly increased.The results showed that exogenous injection of testosterone propionate can reduce the empathic ability of castrated male C57 mice,nevertheless V1 a R antagonist can inhibit the reduction effect of testosterone on empathic behavior.In conclusion,this study found that there was no sexual difference in the empathetic behavior of monogamous mandarin voles,but significant sex difference of was found in C57 mice.The empathetic behavior of male C57 mice was significantly higher than that of female mice.The reduction of testosterone induced by castration resulted in increased empathetic behavior of male C57 mice,accompanied by a significant reduction of AVP and its receptor at the transcription level and protein expression level.Pharmacological experiments further confirmed that testosterone regulates the empathic behavior of male C57 mice by affecting the AVP system.These findings help us to understand the neuroendocrine mechanism underlying empathic behavior and provide us with a laten target for the treatment of low empathy-related psychiatric disorders... |