| Depression is a kind of mental illness with persistent unpleasant mind and cognitive dysfunction,which has caused incalculable damage to our lives and economy.Although there have been long and extensive studies on depression,the mechanism of its occurrence is still not fully understood.Therefore,it is of great significance to study the pathogenesis of depression.Estrogen(17β-Estradiol,E2)plays a very important role in hippocampal function in rats.In female rodents,the beneficial effects of E2 on learning and memory,and emotional behavior are mainly derived from ovarian synthesis of E2.After ovariectomy in female rats,not only does it impair the ability to learn and memory,but it also affects the emotional behavior,resulting in anxiety-like behavior.Exogenous E2 supplementation can improve learning and memory,and anxiety-like behavior can also be improved.Clinical studies have found that hormone therapy(HT)is widely used to control the symptoms of menopause,including prevention of cardiovascular disease,osteoporosis,cognitive decline and senile dementia in elderly women.Subsequent studies found that E2 not only synthesizes in female rat ovaries and hippocampal neurons,regulates synaptic plasticity,but also synthesizes in hippocampal neurons of male rats.It has even been reported that E2 concentration in hippocampus of male rats is higher than that of female rats.However,the specific role of E2 in hippocampal synthesis on the emotional behavior of male rats is not known.To investigate the role of E2 in the hippocampus of male rats and its effect on hippocampal neural plasticity and emotional behavior in male rats,we established a chronic unpredictable mild stress(CUMS)model and used bilateral dorsal hippocampal injections of E2 and E2 synthesis aromatase inhibitor letrozole.Observed the behavioral changes in rats and the expression of hippocampal Kalirin-7 and changes of apical dendritic spines in CA3 pyramidal neurons.The results show:1.Chronic Unpredictable Mild Stress(CUMS)rats exhibited depression-like behavior,the expression of hippocampal Kalirin-7 decreased,and dendritic spine density of pyramidal neurons in CA3 decreased.Compared with the control group,there was a significant difference(P<0.01,P<0.05).After the injection of E2 in CUMS rat,the behavior of rats and the expression of hippocampal Kalirin-7 were significantly improved compared with CUMS group(P<0.05).2.After the rat hippocampus microinjection E2 synthesis of aromatase inhibitor letrozole,compared with the normal control group rats showed depression-like behavior,hippocampal Kalirin-7 expression decreased,CA3 pyramidal neurons dendritic spines density decreased(P<0.01,P<0.05);3.After the rats were given microinjection of E2 to aromatase inhibitor letrozole in normal rats group,the depression-like behavior of rats,the decrease of hippocampal Kalirin-7 expression,and the decrease of dendritic spine density in pyramidal neurons in CA3 region were able to be reduced.Subsequently,exogenously supplemented E2 in the hippocampus was improved(P<0.01,P<0.05);4.CUMS rats and the microinjection of E2 to aromatase inhibitor letrozole in the Hippocampus of normal rats,the rats exhibited depression-like behavior,and the hippocampal glutamate receptor NR 1 and postsynaptic protein PSD95 decreased significantly(P<0.05).Hippocampal injection of E2 significantly improved the role of letrozole(P<0.05).From the above results,we conclude that:hippocampal E2 in male rats plays an important role in the regulation of emotional behaviors.Chronic stress or inhibition of E2 synthesis in the hippocampus can cause depression-like behavior,accompanied by decreased expression of Kalinin-7 in the hippocampus,and neuronal dendritic spine density in CA3 region,NR1,PSD95 expression decreased.Hippocampal microinjection of E2 significantly improved the role of CUMS or the role of bilateral dorsal hippocampal injection of letrozole.The mechanism of action of E2 in hippocampus of male rats is closely related to changes of hippocampal Kalirin-7 expression and dendritic spine densities in CA3 neurons and changes in glutamatergic synaptic plasticity. |
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