ABSTRACT
OBJECTIVE: To observe the effect of maltolate aluminum on synaptic plasticity in the hippocampus of rats and to explore the regulatory effect and mechanism of metabotropic glutamate receptor 1(mGluR1). METHODS: Specific pathogen free healthy adult male SD rats were randomly divided into control group, aluminum group, aluminum agonist group and aluminum antagonist group, 8 rats in each group. The rats in the control group received no treatment; the rats in aluminum group were injected with 5 μL 10 mmol/L maltolate aluminum solution into the lateral ventricle; the rats in aluminum agonists and aluminum antagonist group were injected with 3 μL 10 mmol/L maltolate aluminum solution plus 2 μL 0.1 μmol/L mGluR1 agonist or 2 μL 0.2 μmol/L mGluR1 antagonists into the lateral ventricle, respectively.Maltolate aluminum solution was injected every 2 days and continued for 10 days. After maltolate aluminum exposure, the amplitudes of long-term potentiation(LTP) in hippocampal CA1 region of rats were measured, and the relative expression levels of mRNA and protein of mGluR1, N-methyl-D-aspartate receptor(NMDAR1) and protein kinase C(PKC) in hippocampus tissue of rats were detected by real-time fluorescence quantitative polymerase chain reaction and Western blotting. RESULTS: The amplitude of LTP in hippocampal CA1 region in aluminum group and aluminum agonist group was lower than that in the control group and the aluminum antagonist group(P<0.05). Compared with the control group, the relative expression of mGluR1 mRNA and protein in the aluminum group increased, the relative expression of PKC and NMDAR1 mRNA and protein in the aluminum group decreased(P<0.05). Compared with the aluminum group, the relative expression of mGluR1 mRNA and protein in the aluminum agonist group increased, while the NMDAR1 mRNA decreased(P<0.05); the relative expression of mGluR1 mRNA and protein in the aluminum antagonist group decreased, while the NMDAR1 mRNA and protein increased(P<0.05). Compared with the aluminum agonist group, the relative expression of mGluR1 mRNA and protein decreased, while the NMDAR1 mRNA and protein increased in the aluminum antagonist group(P<0.05). The relative expression level of PKC mRNA and protein in aluminum agonist group and aluminum antagonist group was not statistically significant(P>0.05), and there was no statistical significance in these two groups compared with control group and aluminum group(P>0.05). CONCLUSION: Maltolate aluminum exposure can inhibit synaptic plasticity by inhibiting LTP in hippocampus of rats, and the mechanism may be related to the regulation of NMDAR1 expression by mGluR1.
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Aim To study the regulatory of Jiaweisini-san on expression of hippocampal BDNF, NR1 and dental gyrus ( DG ) neurogenesis in rats with chronic stressed-depression and its possible mechamisms. Methods Chronic unpredictable mild stress was used to establish the rat model of stressed depression. The expression of BrdU, NeuN, brain -derived neurotro-phic factor ( BDNF ) and N-methyl-D-aspartate recep-tor1 ( NR1 ) in hippocampal dental gyrus were detected by fluorescently labeled immunohistochemical method. In addition, BDNFmRNA was detected by in situ hy-bridization. Results Chronic stress could inhibit the proliferation of neural precursors in hippocampal DG ( P<0. 01 );the expression of BDNF decreased signifi-cantly in DG in model rats ( P <0. 01 ) , while the ex-pression of NR1 increased significantly ( P <0. 01 ) . JWSNS and Fluoxetine hydrochloride significantly en-hanced the amount of new proliferating cells and the number of neurons in unit area of DG ( P<0. 01 ) , in-creased the expression of BDNF ( P <0. 01 ) and de-creased the expression of NR1 in DG(P<0. 01). Con-clusion JWSNS could promote the neuronal prolifera-tion in hippocampal DG of rat with chronic stressed-de-pression,and may exert an effect of promoting the pro-liferation of neurons in hippocampal DG by enhancing the expression of BDNF and decreasing the expression of NR1 .
ABSTRACT
Our objective was to investigate the protein level of phosphorylated N-methyl-D-aspartate (NMDA) receptor-1 at serine 897 (pNR1 S897) in both NMDA-induced brain damage and hypoxic-ischemic brain damage (HIBD), and to obtain further evidence that HIBD in the cortex is related to NMDA toxicity due to a change of the pNR1 S897 protein level. At postnatal day 7, male and female Sprague Dawley rats (13.12 ± 0.34 g) were randomly divided into normal control, phosphate-buffered saline (PBS) cerebral microinjection, HIBD, and NMDA cerebral microinjection groups. Immunofluorescence and Western blot (N = 10 rats per group) were used to examine the protein level of pNR1 S897. Immunofluorescence showed that control and PBS groups exhibited significant neuronal cytoplasmic staining for pNR1 S897 in the cortex. Both HIBD and NMDA-induced brain damage markedly decreased pNR1 S897 staining in the ipsilateral cortex, but not in the contralateral cortex. Western blot analysis showed that at 2 and 24 h after HIBD, the protein level of pNR1 S897 was not affected in the contralateral cortex (P > 0.05), whereas it was reduced in the ipsilateral cortex (P < 0.05). At 2 h after NMDA injection, the protein level of pNR1 S897 in the contralateral cortex was also not affected (P > 0.05). The levels in the ipsilateral cortex were decreased, but the change was not significant (P > 0.05). The similar reduction in the protein level of pNR1 S897 following both HIBD and NMDA-induced brain damage suggests that HIBD is to some extent related to NMDA toxicity possibly through NR1 phosphorylation of serine 897.
Subject(s)
Animals , Female , Male , Rats , Cerebral Cortex/metabolism , Hypoxia-Ischemia, Brain/metabolism , Receptors, N-Methyl-D-Aspartate/metabolism , Animals, Newborn , Blotting, Western , Cerebral Cortex/physiopathology , Fluorescent Antibody Technique , Hypoxia-Ischemia, Brain/etiology , Hypoxia-Ischemia, Brain/physiopathology , N-Methylaspartate , Phosphorylation , Rats, Sprague-DawleyABSTRACT
Objectiye To study the mechanism by which transcranial magnetic stimulation (rTMS) affects cognitive dysfunction in vascular dementia (VD). Methods Thirty-six male Wistar rats were randomly divided into a control group, a VD group, a low frequency rTMS group and a high frequency rTMS group. Two-vessel occlusion was employed to induce VD models. Low frequency rTMS group rats were given 0.5 Hz rTMS for six weeks. High frequency rTMS group rats were given 5 Hz rTMS for six weeks. Morris' water maze test was used to measure their spatial learning ability and memory. The ultrastructures of the synapses in the four groups were detected with transmission electron microscopy. The expression of synaptophysin (SYN), brain derived neurotrophic factor (BDNF) and Nmethyl-D-aspartate receptor 1 ( NMDAR1 ) mRNA and protein in the hippocampus were determined by real-time PCR and Western blotting. Results The behavior and morphology of the rats treated with rTMS improved. The average expression of SYN, BDNF and NMDAR1 mRNA and protein in the low frequency rTMS group and the high frequency rTMS group were significantly higher than in the VD group. Conclusion rTMS can provide a rehabilitative effect for VD. The mechanism might be associated with enhancing the expression of SYN, BDNF and NMDAR1 in the hippocampus.
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Objective: To observe the effect of auricular needling on abilities of learning and memory as well as expression of NMDAR1 in rats with vascular dementia(VD).Methods:VD rat model was established by blocking 4-vessel.The immunohistochemistry method was used to detect the changes of NMDAR1 expression,the Y-type maze test was used to measure the abilities of learning and memory.Results:There were slight expression of NMDAR1cells in the brain tissue of normal group.Compared with the normal group,the expression of NMDAR1 positive cells in model group were significantly enhanced,but the average optical density is obvious reduced(P