title: Role of NMDA receptors in noise-induced tau hyperphosphorylation in rat hippocampus and prefrontal cortex.
abstract: Chronic noise exposure has been associated with abnormalities in glutamate (Glu)-NMDAR signaling and tau hyperphosphorylation. However, further studies are necessary to clarify potential causal relationships. The aim of the present study was to evaluate the role of NMDA receptors in noise-induced tau hyperphosphorylation in the rat hippocampus and prefrontal cortex. Male Wistar rats were randomly divided into three groups in the present study: control with isotonic saline instillation (n=10); noise exposure (100 dB SPL white noise, 4h/d × 14d) and treated with saline (n=10); and noise exposure and treated with MK-801 (0.5mg/kg, intraperitoneally; n=10). The levels of tau phosphorylated at Ser202 and Ser396, and proteins involved in hyperphosphorylation, namely glycogen synthase kinase 3β (GSK3β) and protein phosphatase 2A (PP2A), were measured in the hippocampus and prefrontal cortex (PFC) after the last noise exposure. We showed that phosphorylated tau levels were enhanced in noise-exposed-rat hippocampus and PFC. MK-801 decreased the hyperphosphorylation of tau at Ser202 and Ser396 sites in the hippocampus and PFC. Furthermore, MK-801 reversed noise-induced GSK3β overexpression but had no significant effect on PP2A levels. This suggests that MK-801 protects against chronic-noise-induced tau hyperphosphorylation in the hippocampus and PFC. These findings demonstrate that Glu-NMDAR signaling may be involved in triggering aberrant tau hyperphosphorylation in the hippocampus and PFC after chronic noise exposure.
authors.affiliation: Department of Occupational Hygiene, Institute of Health and Environmental Medicine, Tianjin 300050, China.
authors.forename: Kang
authors.initials: K
authors.lastname: Li
authors.affiliation: Bethune International Peace Hospital of PLA, Shijiazhuang 050082, China.
authors.forename: Hengchuan
authors.initials: H
authors.lastname: Jia
authors.affiliation: Department of Occupational Hygiene, Institute of Health and Environmental Medicine, Tianjin 300050, China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: She
authors.affiliation: Department of Occupational Hygiene, Institute of Health and Environmental Medicine, Tianjin 300050, China. Electronic address: iamcuib@sina.com.
authors.forename: Bo
authors.initials: B
authors.lastname: Cui
authors.affiliation: Department of Occupational Hygiene, Institute of Health and Environmental Medicine, Tianjin 300050, China.
authors.forename: Na
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Occupational Hygiene, Institute of Health and Environmental Medicine, Tianjin 300050, China.
authors.forename: Xuewei
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Occupational Hygiene, Institute of Health and Environmental Medicine, Tianjin 300050, China.
authors.forename: Chuanxiang
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of Occupational Hygiene, Institute of Health and Environmental Medicine, Tianjin 300050, China.
authors.forename: Gaihong
authors.initials: G
authors.lastname: An
authors.affiliation: Department of Occupational Hygiene, Institute of Health and Environmental Medicine, Tianjin 300050, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Ma
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009622:Noise; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D054648:Protein Phosphatase 2 / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D016875:tau Proteins; D016291:Dizocilpine Maleate; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D038362:Glycogen Synthase Kinase 3; C582184:Ppp2r2a protein, rat; D054648:Protein Phosphatase 2
keywords: MK-801; NMDAR; Noise; Tau hyperphosphorylation