An Experimental Study Of Brain-derived Neurotrophic Factor Intervention In Neonatal Dexamethasone-related Mental Disorder

Brain-derived neurotrophic factor(BDNF),which regulates the neuronal survival,differentiation and synaptic plasticity,has been proved to play a critical role in the pathology and treatment of several psychiatric disorders including depression.Dexamethaone(DEX)are indicated for a number of conditions in perinatal medicine,however,the long-term impact of early-life DEX exposure on BDNF and its signaling pathway molecules Me CP2,p CREB expression in hippocampus remains unknown.Here we found that neonatal DEX(ND)exposure leads to insignificant change of BDNF,Me CP2,p CREB expression levels in the adulthood,albeit increased hyperanxious and depressive-like behaviors.However,the bdnf m RNA and BDNF protein levels were significantly reduced in all the hippocampal subregions during the developmental stages including the perinatal period and puberty,while the expression of Me CP2,p CREB significantly increased.We conclude that early life DEX exposure leads to a persistent disturbance of BDNF signaling during the developmental stages,which might be associated with the life-long impairment of hippocampal function.Puberty is another key period of brain development and structural remodeling.ND exposure can lead to a decreased BDNF expression in adolescence and accompanied with increased hyperanxious and depressive-like behaviors in adulthood.Therefore,overexpression of BDNF in puberty becomes a possible option to retrieve the harmful behaviors in adulthood caused by ND exposure.Thus,we constructed an adeno-associated virus vector carrying the BDNF gene,and prepared the corresponding adeno-associated virus.Stereotaxic injection of adeno-associated virus into the hippocampus region of mice to make over-expression of adeno-associated virus during puberty.We found that overexpression of BDNF in ND-exposed mice resulted in a significant increase of BDNF expression in the adult hippocampus region,which was also accompanied by a certain degree of anxiety-like,depression-like behaviors and spatial memory repair.Besides,after overexpression of BDNF during puberty in ND exposed mice,the synaptic protein expression of PSD95,Synapsin I,and apoptosis inhibitor expression of Bcl-2 in the hippocampus of adult mice all showed amarkedly enhanced state.We conclude that overexpression of BDNF during adolescence can improve the phenotype of undesirable behavior caused by ND exposure,which is also accompanied by enhanced synaptic germination and increased ability to suppress apoptosis.