The Study Of Effects Of Noise Exposure On Cognition And Mechanisms In Hippocampus

With rapid development in modern industry and weapon equipments, noise pollution is on an ever-increasing trend, both in industrial areas and military operation areas. The WHO document indicated that noise exposure may lead to many detrimental effects including hearing impairment; psychophysiological, mental-health and performance effects; effects on residential behaviour and annoyance. It has been documented in both laboratory subjects and in workers exposed to occupational noise that noise adversely affects cognitive task performance. Cognition is coordinated with Glu-NMDAR system in different brain regions especially hippocampus. However, the advanced mechanisms responsible for noise-induced cognitive impairment are not well understood. The aim of this research is to study the effects of acute and chronic noise exposure on spatial learning and memory and mechanism in hippocampus. So experiments were performed to probe the effects and mechanisms of high intensity impulse noise acute exposure and medium intensity continuous steady white noise chronic exposure on cognition and hippocampus. It is helpful to has profound insight into the effects of noise exposure on CNS, as well as to provide experimental basis for precaution.Male SD rats were exposed to high intensity impulse noise or medium intensity continuous steady state white noise. Morris water maze(MWM) and evoked potential were respectively used to examine the changes of spatial cognition and event related potential P300. Effects of noise on Glu-NMDAR system, tau phosphorylation and neural state in hippocampus were investigated by means of high performance liquid chromatogram, Western blot, immunohistochemistry and TUNNEL respectively. To probe the roles and in-depth mechanisms of Glu-NMDAR system in noise-induced cognitive and hippocampal impairment, we used Memantine hydrochloride,a noncompetitive antagonist of NMDAR, as an intervention. The research was divided into three parts, and the grouping of test animals and main findings were as follows. 1. Effects of high intensity impulse noise acute exposure on cognition and hippocampus.Male SD rats used in the study were randomly divided into 5 groups: control group (CTR), and groups 0h (IMP0), 3h(IMP3), 6h(IMP6) and 24h(IMP24) after impulse noise exposure. Animals were exposed 20 times to impulse noise with a peak sound pressure level 165±1dB and duration of 100 msecs.After impulse noise exposure, the latency of hidden-plat-from-acquisition in MWM was in upward trend, and the performance in probe trial testing of rats in IMP0 and IMP3 groups decreased significantly, indicating that impulse noise exposure could induce cognitive impairment. The latency of ERP P300 in IMP0 group was significantly higher than CTR group, while latency in IMP3, IMP6 and IMP24 groups recovered and had no significantly difference compared with CTR group. The concentrations of Glu and Asp were significantly increased in all IMP groups, as well as Gly in IMP24 group. Western blot showed that the expression of NR2B in hippocampus increased in all IMP groups, and immunohistochemistry staining also showed that the expression of NR2B in CA1, DG and CA3 regions increased after impulse noise exposure, especially in DG region. Impulse noise acute exposure caused not only an early phase reversible tau phosphorylation, but also a later phase tau phosphorylation after 6 h, and immunohistochemistry staining showed that this tendency was more significant in CA1 and DG regions. TUUNEL staining showed that a few positive cells existed only in DG region in IMP6 and IMP24.2. Effects of medium intensity continuous steady white noise chronic exposure on cognition and hippocampus.Male SD rats were grouped as: control group(CTR); MWM training group(L): MWM training and testing started at 14:00 from experimental day 26 to 30; white noise chronic exposure group(N): 100 dB white noise, 4 h /d×30d, from 8:00 to 12:00; white noise chronic exposure followed by MWM training group(NL): noise exposure as Group N, followed by MWM training as in Group L.After chronic noise exposure, the latency of hidden-plat-from-acquisition in MWM was markedly increased in test day 1 an 3 and in upward trend in test day 2 an 4, and the performance in probe trial testing of rats in NL group decreased significantly, indicating that chronic noise exposure could induce cognitive impairment. The latency of ERP P300 in N and NL groups was significantly higher than CTR and L groups the 20 and 30 experimental day. The concentration of glutamate was significantly increased in groups N and NL,whereas GABA decreased markedly. Western blot showed that the expression of NR2B in hippocampus reduced after chronic noise exposure, and immunohistochemistry staining also showed that the expression of the NR2B was significantly decreased in CA1,CA3 and DG regions in group N and CA1 and CA3 regions in group NL as compared with groups CTR and L. Western blot and immunohistochemistry staining both showed chronic noise exposure caused expression of p-Tau increased markedly in CA1,CA3 and DG regions in hippocampus, and rate of increase was higher than that after impulse noise exposure. TUUNEL staining showed that lots of positive cells existed in CA1,CA3 and DG regions in N and NL groups,whereas few in groups CTR and L. All above data analyzed by two-factor ANOVA (general linear model) tests showed that only noise exposure had significant effects on experiment result.3. Role of antagonist of NMDAR in relief of noise-induced cognitive and hippocampal impairment.Male SD rats were grouped as: control group (CTR), memantine administration group(M), impulse noise exposure group(IMP) and impulse noise exposure after memantine administration group(M+IMP). Memantine was administered 3h before impulse noise exposure in M and M+IMP group (10mg/kg).After MH intervention, performance in MWM and P300 latency of M+IMP group had a tendency to retrieval compared with IMP group and no significant difference with CTR group. Tau phosphorylation was inhibited markedly in hippocampus of M+IMP group, of which expression of p-Tau recovered to control level.To sum up, we can draw conclusions as follow. First, both acute and chronic noise exposure can induced cognitive impairment. Second, aberrant hyperphosphorylation of tau induced by abnormal Glu-NMDAR system in hippocampus can cause neuron dysfunction or death, which may be common pathway of hippocampal impairment induced by acute or chronic noise exposure. Third, abnormities in Glu-NMDAR system induced by noise exposure play key roles in tau hyperphosphorylation, which can be inhibited by memantine.