| Objective:Affective disorder is a series of diseases, which core symptoms are significant and long-lasting mood changes caused by many reasons. Depression's incidence rate was the highest among the affective disorder, it can occur in every stage of one's life, especially in juvenile or adolescent. Up to now, about million people were suffering from it, the society is threaten by the high incidence rate, recurrence rate and also the rate about suicide of the depression. A substantial number of human epidemiological data, as well as experimental studies with animals, suggest that prenatal stress (PS) is closely related with abnormal behavior and mental and cognition disorder in some disease, but it is still unclear about the pathology and mechanism of it. Glutamate, the main excitatory neurotransmitter of the central nervous system, is considered to be associated with the neuronal excitotoxicity in many diseases. Glutamate with its receptors may have some important roles in depression. In this study, we aimed to investigate the effects of prenatal stress on mGluR1, mGluR5, BDNF expression in offspring rat hippocampus, striatum, the prefrontal cortex, also aimed to improve our knowledge in molecule mechanisms about offspring rats'depressive-like behavior caused by prenatal restraint stress. And this may have beneficial to health care of newborn and pregnant women.Methods:In this study, a rat model of prenatal constraint stress was adopted, the pregnant rats were randomly divided into late-prenatal stress group, mid-prenatal stress group and control group(n=6 for each grouup). Late-stressed group pregnant rats were given restraint stress (3a times/day for 7days and 45 minutes each time) at the 14-20d of gestation, mid-stressed group pregnant rats were given restraint stress (45 minutes each time,3 times/day for 7 days)at the 7-13d of gestation 1-month-old offspring rats.Control group pregnant rats were not given any restraint stress.1-month-old offspring rats were used in all experiments. The depressive-like behavior of offspring rats were measured by forced swimming test (FST). The expression of mGluR1,mGluR5 in hippocampus,striatum and the prefrontal cortex were determined by Western-blot. Furthermore, the transcription level of BDNF in hippocampus,striatum and the prefrontal cortex were detected by RT-PCR.Results:1. The effects of prenatal restraint stress on depressive-like behavior of offspring rats: 1) Female offspring:The time spent immobile was significantly increased in female offspring rats of late-stressed group. Compared with mid-stressed group and control group, there were significantly differences (261.67±57.03 vs 148.75±54.16, P<0.05; 261.67±57.03 vs 147.67±50.53, P<0.05), and there was no significantly difference between mid-stressed group and control group;2) Male offspring:The time spent immobile was significantly increased in male offspring rats of late-stressed group, and there was significantly difference between mid-stressed group and late-stressed group (201.92±57.46 vs 119.67±49.57, P<0.05), both mid-stressed group and control group, late-stressed group and mid-stressed group had no significantly differences between each other;3) Comparison of male offspring and female offspring:Compared with male offspring rats, the female rats spent longer immobile time (261.67±57.03 vs 201.92±57.46, P<0.05), and there was no significantly difference between female and male offspring rats in both mid-stressed group and control group(P>0.05)2. The effects of prenatal restraint stress on mGluR1 expression in offspring rat hippocampus, striatum, the prefrontal cortex:Hippocampus:1) Female offspring:The expression of mGluR1 was increased in offspring hippocampal neurons of stress group, and there was significantly increased in offspring rats between late-stressed group and control group (1.18±0.28 vs 0.69±0.20, P<0.05), and also in offspring rats between late-stressed group and mid-stressed group (1.18±0.28 vs 0.77±0.21, P<0.05)., and there was no significantly difference between mid-stressed group and control group(P>0.05);2) Male offspring:The expression of mGluRl was increased in offspring hippocampal neurons of stress group, and there was significantly increased in offspring rats between late-stressed group and control groupl.14±0.22 vs 0.67±0.27, P<0.05), and also in offspring rats between late-stressed group and mid-stressed group (1.14±0.22 vs 0.70±0.14, P<0.05), and there was no significantly difference between mid-stressed group and control group(P>0.05);3) Comparison of male offspring and female offspring:There was no significantly difference on the expression level of mGluR1 between male and female offspring rats in both control group and stress group(P>0.05).Striatum:There was no significantly differences between stress group and control group, compared with the female offspring rats, the male offspring rats have no significantly differences;The prefrontal cortex:1) Female offspring:The expression of mGluRl was increased in offspring hippocampal neurons of stress group, and there were significantly increased in offspring rats between late-stressed group and control group (1.25±0.34 vs 0.77±0.27, P<0.05), both mid-stressed group and control group, late-stressed group and mid-stressed group had no significantly differences between each other (P>0.05); 2) Male offspring:The expression of mGluRl was increased in offspring hippocampal neurons of stress group, and there were significantly increased in offspring rats between late-stressed group and control group (1.15±0.32 vs 0.66±0.30, P<0.05), both mid-stressed group and control group, late-stressed group and mid-stressed group had no significantly differences between each other (P>0.05);3) Comparison of male offspring and female offspring:There was no significantly difference on the expression level of mGluRl between male and female offspring rats in both control group and stress group(P>0.05).3. The effects of prenatal restraint stress on mGluR5 expression in offspring rat hippocampus, striatum, the prefrontal cortex:Hippocampus:1) Female offspring:The expression of mGluR5 was increased in offspring hippocampal neurons of stress group, and there were significantly increased in offspring rats between late-stressed group and control group (1.38±0.48 vs 0.76V0.26,p<0.05), and also in offspring rats between late-stressed group and mid-stressed group(1.38±0.48 vs 0.84±0.20, P<0.05), and there was no significantly difference between mid-stressed group and control group(p>0.05);2) Male offspring:The expression of mGluR5 was increased in offspring hippocampal neurons of stress group, and there were significantly increased in offspring rats between late-stressed group and control group (1.64±0.36 vs 0.93±0.13, P<0.05), and also in offspring rats between late-stressed group and mid-stressed group(1.64±0.36 vs 1.15±0.25, P<0.05), and there was no significantly difference between mid-stressed group and control group(p>0.05);3) Comparison of male offspring and female offspring:There was no significantly difference on the expression level of mGluR5 between male and female offspring rats in both control group and stress group(P>0.05).Striatum:1) Female offspring:The expression of mGluR5 was increased in offspring hippocampal neurons of stress group, and there were significantly increased in offspring rats between late-stressed group and control group (1.10±0.33 vs 0.55±0.12, P<0.05), and also in offspring rats between mid-stressed group and control group ((0.79±0.18 vs 0.55±0.12, P<0.05), and there was no significantly difference between mid-stressed group and late-stressed group(P>0.05);2) Male offspring:The expression of mGluR5 was increased in offspring hippocampal neurons of stress group, and there were significantly increased in offspring rats between late-stressed group and control group (1.14±0.33 vs 0.69±0.31, P<0.05), and also in offspring rats between late-stressed group and mid-stressed group (1.14±0.33 vs 0.70±0.21, P<0.05), and there was no significantly difference between mid-stressed group and control group(P>0.05);3) Comparison of male offspring and female offspring:There was no significantly difference on the expression level of mGluR5 between male and female offspring rats in both control group and stress group(P>0.05).The prefrontal cortex:1) Female offspring:The expression of mGluR5 was increased in offspring hippocampal neurons of stress group, and there were significantly increased in offspring rats between late-stressed group and control group (1.12±0.23 vs 0.61±0.23, P<0.05), and also in offspring rats between late-stressed group and mid-stressed group (1.12±0.23 vs 0.64±0.26, P<0.05), and there was no significantly difference between mid-stressed group and control group(P>0.05);2) Male offspring:The expression of mGluR5 was increased in offspring hippocampal neurons of stress group, and there were significantly increased in offspring rats between late-stressed group and control group (1.15±0.34 vs 0.71±0.20, P<0.05), and also in offspring rats between late-stressed group and mid-stressed group (1.15±0.34 vs 0.81±0.14, P<0.05), and there was no significantly difference between mid-stressed group and control group(P>0.05);3) Comparison of male offspring and female offspring:There was no significantly difference on the expression level of mGluR5 between male and female offspring rats in both control group and stress group(P>0.05).4. The effects of prenatal restraint stress on the transcription level of BDNF in offspring rat hippocampus,striatum and the prefrontal cortex:Hippocampus:1) Female offspring:The transcription level of BDNF was decreased in offspring hippocampal neurons of stress group, and there was significantly decreased in offspring rats between late-stressed group and control group (0.61±0.33 vs 1.22±1.08, P<0.05), Compared to the mid-stressed group, there were no significantly differences among late-stressed group and control group;2) Male offspring:The transcription level of BDNF was decreased in offspring hippocampal neurons of stress group, and there was significantly decreased in offspring rats between late-stressed group and control group (0.70±0.21 vs 1.21±0.21, P<0.05), Compared to the mid-stressed group, there were no significantly differences among late-stressed group and control group;3) Comparison of male offspring and female offspring:There was no significantly difference on the transcription level of BDNF between male and female offspring rats in both control group and stress group(P>0.05).Striatum:1) Female offspring:The transcription level of BDNF was decreased in offspring striatum neurons of stress group, and there was significantly decreased in offspring rats between late-stressed group and control group (0.72±0.21 vs 1.28±0.35, P<0.05), Compared to the mid-stressed group, there were no significantly differences among late-stressed group and control group;2) Male offspring:The transcription level of BDNF was decreased in offspring striatum neurons of stress group, but there were no significantly differences among each other;3) Comparison of male offspring and female offspring:There was no significantly difference on the transcription level of BDNF between male and female offspring rats in both control group and stress group(P>0.05).The prefrontal cortex:1) Female offspring:Compared to the control group, there was little increase in mid stressed group; There were significantly decreased in offspring the prefrontal cortex neurons between late-stressed group and mid-stressed group (0.72±0.21vs1.37±0.74, P<0.05); and also between late-stressed group and control group (0.72±0.21vs1.28±0.35, P<0.05);2) Male offspring:Compared to the control group, there was little increase in mid stressed group; There were significantly decreased in offspring the prefrontal cortex neurons between late-stressed group and mid-stressed group (1.13±0.56 vs 1.60±0.36, P<0.05); and also between late-stressed group and control group (0.99±0.56 vs 1.49±1.50,p<0.05);3) Comparison of male offspring and female offspring:There was no significantly difference on the transcription level of BDNF between male and female offspring rats in both control group and stress group(P>0.05).Conclusion:The result above indicated that prenatal stress could cause depressive-like behavior of offspring rats.The prenatal stress animal models could be used to study the etiology of depression. mGluRâ… with BDNF play an important role in it. The increase of the expression of mGluR1 and mGluR5 proteins play a part in depression, which may indicate that the prenatal stress can not only cause the abnormality of glutamic system in pups, but strengthen the toxic effect of glutamic as well. On one hand, the decrease of BDNF cut down the protection of BDNF to the neuronal, on the other, it also strengthen the toxic effect of glutamic, advance the happen of depression. Therefore, the complex mechanism concerned is to be further studied.
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