The Effects Of Early Life Stress On The Expression Of NMDA Receptors Subunits And C-fos In The Forebrain Of Rodents

As clinical research and epidemiological survey shows, early life stress is oneof the important risk factors for mental disease. Early negative life event willincrease an individual’s susceptibility to mental illness which has the environmentalrisk, such as anxiety, depression. The forebrain (e.g. hippocampus and prefrontalcortex) is not only the high regulating center for stress, but also the important brainareas involved in cognitive function, which has a important place in the study of themechanism of mental illness. In animal model studies, the change of the synapticplasticity and cognitive impairment in forebrain which induced by early life stressprovides a unique perspective for the mental disease pathogenesis research.Glutamate is an important central excitatory neurotransmitter, which combined withthe postsynaptic membrane NMDA receptor, plays an important physiological role.Animal studies have shown that early MK-801treatment induce cognitiveimpairment. This research chooses drug injection to mimic the early life stress, theninvestigate whether the developmental expression of NMDA receptor subunits inforebrain is affected by early life stress.The first experimentObjective: This research chooses injection of MK-801to mimic the early life stress,then investigate whether the developmental expression of NMDA receptor subunitsis affected by early life stress.Methods: In the experiment, rats were administrated subcutaneously with MK-801 or normal saline from postnatal day(PND)5to PND14. The expression of NMDAreceptor subunits (NR1, NR2A and NR2B) in hippocampus and prefrontal cortex inadult rats have been tested.Results:1.In neonatal period(PND15), there were no significant differences on the expressionof NR1, NR2A, NR2B in prefrontal cortex and hippocampus between the twogroups(P>0.05);2.In adolescence(PND42), there were no significant differences on the expression ofNR1, NR2A, NR2B in prefrontal cortex and hippocampus between the twogroups(P>0.05);3.In adulthood(PND70), the expression of NR1, NR2A in hippocampus in researchgroup was significantly higher than control group[NR1:（149.55±12.08） vs.（100.00±14.34）; NR2A:（171.54±8.88）vs.（100.00±22.83）],(P<0.05); theexpression of NR2B in hippocampus and the expression of NR1, NR2A, NR2B inprefrontal cortex have been showed no diffrences between the two groups(P>0.05).After neonatal repeated treatment of MK-801, the expression of NMDAreceptor subunits (NR1, NR2A) is up-regulated in hippocampus in adulthood. Theresults suggest that neonatal blockade of the NMDA receptors will influence thegrowth and development of the nervous system, although the mechanismsunderlying these changes await further investigation, which has an important guidingsignificance for clinical treatment and prognosis.The second experimentObjective: This research investigated the effects of early life stress on the expressionof c-fos in hippocampus and prefrontal cortex in adult mice.Methods: The limited nesting and bedding material paradigm was performed duringPND2-PND9, then the experiment detected the expression of c-fos in hippocampus and prefrontal cortex in adult mice.Results:1.There were no significant differences on the expression of c-fos in prefrontalcortex between the stress group and control group(P>0.05);2.There were no significant differences on the expression of c-fos in hippocampusbetween the stress group and control group(P>0.05);In conclusion, the expression of c-fos in the stress group is not diffrent from thecontrol group, which suggests that the early life stress have not affected the basicexpression of c-fos in adult mice.Conclusion The research indicated that the stress in early life interact with NMDAsystems and cause the long-term dysplasia, suggest that the neural development isaffected for long time. Meanwhile, the early life stress has no effect on the the basicexpression of c-fos in adult mice, which provide evidences for the next experimentto study the effect of early life stress and the expression of c-fos after the behavioraltest, which provide an important basis for studying the mechanisms of treatment andprevention in mental illness.