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Study on mGluRs Involved in Depressive Behaviour Induced by Prenatal Stress in Offspring Rats

Author: SongZuo
Tutor: ZhuZhongLiang
School: Northwestern University
Course: Zoology
Keywords: Prenatal stress Depressive disorder Metabotropic glutamate receptor Brain-derived neurotrophic factor
CLC: R749.4
Type: Master's thesis
Year: 2011
Downloads: 45
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Abstract

Objective: affective disorders is obvious and lasting emotional or mood changes as the main clinical characteristics of a group of diseases caused by a variety of reasons, which Youyi highest depressive disorder morbidity in all ages have occurred, but most occurred in human childhood or adolescence, afflicts millions of people worldwide, and its high incidence and high recurrence rate and the high rate of suicide caused great threat to society. Zoology experiments and human epidemiological studies show that prenatal stress and offspring acquired abnormal behavior is closely related to certain disease states, particularly significant in the spiritual and intellectual aspects, but the specific mechanism unclear. Previous studies have shown that the the glutamate excitotoxicity role involved in the damage of the nerve cells in the pathogenesis of many diseases, glutamic acid and its receptor interactions may play a role in depressive disorders. On this basis, we choose a prenatal restraint stress in rats offspring as the object of study, to investigate the neuronal cells in various brain regions of rat offspring prenatal restraint stress metabotropic glutamate receptor 1, 5; expression of brain-derived neurotrophic factor, and further reveal the molecular mechanisms of prenatal stress effects on the rat offspring depressive-like behavior for perinatal care of pregnant women, and promote the scientific theories of early childhood brain development basis. Methods: In this study, using rat restraint prenatal stress model: 18 pregnant rats were randomly divided into late stress group (n = 6), Interim stress group (n = 6), control group (n = 6). Late stress group of pregnant rats given 14-20 days to restraint stress three times a day, every 45 minutes; interim stress group mothers to give restraint stress during pregnancy on days 7-13, 3 times a day every 45 minutes; control group was not given any treatment. 1-month-old rat offspring into the experiment. Application detects forced swimming test in rat offspring depressive-like behavior; application of protein immunoblotting were detected in rat offspring hippocampus, striatum, frontal cortex metabotropic glutamate receptor 1 (of mGluR1) metabotropic Valley acid receptor 5 (mGluR5); Using semi-quantitative reverse transcription - polymerase chain reaction detection in rat offspring hippocampus, striatum, frontal lobe neurons, brain-derived neurotrophic factor transcription level. Results: 1. Prenatal stress on depression-like behavior in rat offspring: 1) female offspring: late stress group offspring rats, compared with mid-stress group and control group offspring rats not dynamic time, have a significant extension of (261.67 ± 57.03 vs 148.75 ± 54.16, P lt; 0.05; 261.67 ± 57.03 vs147.67 ± 50.53, P lt; 0.05), while the mid-stress group and control group offspring rats No significant differences; 2) for male offspring: late stress group offspring rats, rats immobility time compared with the control group offspring significantly prolonged (201.92 ± 57.46 vs 119.67 ± 49.57, P lt; 0.05 ), while the mid-stress group and the control group, and late stress group had no significant difference; 3) female and male offspring comparison: late stress group female offspring rats fixed the time was significantly longer than that for male offspring (261.67 ± 57.03 vs 201.92 ± 57.46, P lt; 0.05) between the control group and the medium-term stress group of male and female offspring were not statistically different (P gt; 0.05). Prenatal stress on offspring rat brain metabotropic glutamate receptor 1 expression: the hippocampus: 1) Female Offspring: stress group compared with the control group offspring rats mGluRl-expression were increased rat offspring of the late stress group compared with the control group (1.18 0.28 vs 0.69 ± 0.20, P lt; 0.05) and medium-term stress group (1.18 ± 0.28 vs0.77 ± 0.21, P lt; 0.05) were significant differences ; interim stress group offspring rats and control group no significant difference; 2) for male offspring: stress group compared with the control group the offspring rats mGluRl expression levels increased late stress group offspring rats. compared with the control group (1.14 ± 0.22 vs 0.67 0.27, P lt; 0.05) and medium-term stress group (1.14 ± 0.22 vs0.70 ± 0.14, P lt; 0.05) were significantly different; mid-stress group offspring no statistically significant difference between the mice and the control group; 3) between male and female: male and female offspring rats in each group there was no significant difference (P gt; 0.05). The striatum: between stress and control groups, male and female groups had no significant difference (P gt; 0.05). Frontal cortex: 1) Female Offspring: stress group compared with the control group offspring the rat mGLuRl expression were increased by late stress group offspring rats compared with the control group, a significant difference (1.25 ± 0.34 vs 0.77 ± 0.27 , P lt; 0.05); interim stress group and control group, and the late stress group offspring rats were not statistically different (P gt; 0.05); 2) for male offspring: stress group compared with the control group of offspring the rat mGluR1 expression levels increased and late stress group offspring rats compared with the control group, a significant difference (1.15 ± 0.32 vs 0.66 0.30, P lt; 0.05); interim stress group and the control group and late stress group progeny The rats were not statistically different (P gt; 0.05); 3) between the male and female: male and female offspring rats in each group had no significant difference (P gt; 0.05). 3. Prenatal stress on offspring rat brain metabotropic glutamate receptor 5 expression the hippocampus in: 1) female offspring: stress group compared with the control group offspring mGluR5 expression in neurons amount rise late stress group the offspring rats than in the control group (1.38 0.48 vs 0.76 ± 0.26, P lt; 0.05), as well as medium stress group (1.38 ± 0.48 vs 0.84 ± 0.20, P lt; 0.05) were significantly difference, between mid-stress group offspring rats and a control group, no significant difference (P gt; 0.05); 2) for male offspring: stress group compared with the control group of offspring in neurons mGluR5 expression levels rise late stress group the offspring rats than in the control group (1.64 0.36 vs 0.93 ± 0.13, P lt; 0.05), as well as medium stress group (1.64 ± 0.36 vs 1.15 ± 0.25, P lt; 0.05) were significantly difference between mid-stress group offspring rats and a control group, no significant differences (P gt; 0.05); 3) between the male and female: male and female offspring rats in each group were not significantly different (P gt; 0.05). Striatum: 1) Female Offspring: stress group compared with the control group offspring mGluR5 expression levels increased in neurons, late stress group offspring rats compared with the control group, a significant difference (1.10 ± 0.33 vs 0.55 0.12, P lt; 0.05), medium-term stress group than in the control group had significant difference (0.79 0.18 vs 0.55 ± 0.12, P lt; 0.05), while the mid-stress group offspring rats and late stress group between no significant difference (P gt; 0.05); 2) for male offspring: stress group compared with the control group offspring mGluR5 expression levels increased in neurons, late stress group offspring rats compared with the control group (1.14 ± 0.33 vs 0.69 ± 0.31, P lt; 0.05), as well as medium stress group (1.14 ± 0.33 vs 0.70 ± 0.21, P lt; 0.05) There was no statistical difference between the significant difference between the control group and the medium-term stress group ( P gt; 0.05); 3) male and female: male and female offspring rats in each group had no significant sex difference (P gt; 0.05). MGluR5 expression levels increased in the prefrontal cortex: 1) Female Offspring: stress group compared with the control group of offspring in neurons, the the advanced stress group offspring rats compared with the control group (1.12 ± 0.23 vs 0.61 ± 0.23, P lt; 0.05), as well as medium stress group (1.12 ± 0.23 vs 0.64 ± 0.26, P lt; 0.05) There was no significant difference between the control group and the medium-term stress group a significant difference (P gt; 0.05); 2) for male offspring: stress group compared with the control group offspring mGluR5 expression levels increased in neurons, late stress group offspring rats compared with the control group (1.15 ± 0.34 vs 0.71 ± 0.20, P lt; 0.05) , as well as medium stress group (1.15 ± 0.34 vs 0.81 ± 0.14, P lt; 0.05) significant statistical difference between the difference between the control group and the medium-term stress group (P gt; 0.05); 3) between male and female: male and female offspring rats in each group had no significant difference (P gt; 0.05). Hippocampus of prenatal stress on offspring rat brain, brain-derived neurotrophic factor transcription level: 1) Female Offspring: stress group compared with the control group of offspring rats BDNF mRNA expression were dropped late in rat offspring stress group compared with the control group, a significant difference (0.61 0.33vs1.22 ± 1.08, P lt; 0.05), while there was no between offspring rats and the control group, stress group in the mid and late stress group significant difference (P gt; 0.05); 2) for male offspring: the stress group compared with the control group of offspring rats BDNF mRNA expression were decreased in rat offspring of the late stress group compared with the control group, a significant difference (0.70 ± 0.21vs1.21 ± 0.21, P lt; 0.05); offspring rats of the control group and the interim group, and late stress group and the medium-term group had no statistical difference (P gt; 0.05); 3) male and female between: male and female offspring rats in each group had no significant difference (P gt; 0.05). Striatum: 1) Female Offspring: stress group compared with the control group offspring rat BDNF mRNA expression were decreased in rat offspring of the late stress group compared with the control group had significant difference (0.72 ± 0.21vs1.28 ± 0.35, P lt; 0.05); offspring rats of the control group and the interim group, and late stress group and the interim group had no significant difference; 2) for male offspring: stress group offspring rats. BDNF mRNA expression levels of the control group decreased, but no significant differences (P gt; 0.05); 3) male and female: male and female offspring rats in each group had no significant difference. Frontal cortex: 1) Female Offspring: Interim stress group offspring rats compared with the control group BDNF mRNA expression levels increased, but there was no significant difference (P gt; 0.05); late stress group than in the mid-stress group significantly decreased (0.72 ± 0.21vs1.37 ± 0.74, P lt; 0.05); the advanced stress group compared with the control group is also significantly decreased (0.72 ± 0.21vs1.28 ± 0.35, P lt; 0.05): 2) male offspring: Interim stress group offspring rats compared with the control group BDNF mRNA expression levels increased, but no significant differences (P gt; 0.05); late stress group compared with the mid-term stress group was significantly decreased (1.13 ± 0.56vs1.60 ± 0.36, P lt; 0.05); late stress group compared to the control group also decreased significantly (0.99 0.56vsl.49 ± 1.50 P lt; 0.05); 3) between male and female: male and female offspring mouse between groups, there was no significant difference (P gt; 0.05). Conclusions: prenatal stress cause offspring rats produces symptoms of major depressive disorder, prenatal restraint stress model can be used to study animal models of depression, can reflect the behavior of the depressive disorder. mGluR I and BDNF in which play an important role. the mGluRl and mGluR5 protein expression of the amount of the increase is closely related to depression, to offspring rats glutamatergic system disorder caused by prenatal stress, and strengthen the toxic effects of glutamate. BDNF decline on the one hand to reduce the protection of the neurons survived, the other hand, to strengthen the role of glutamate toxicity strengthen the occurrence of depression. Specific complex mechanism should be further researched.

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