Region-Specific Expression of Tau, Amyloid-β Protein Precursor, and Synaptic Proteins at Physiological Condition or Under Endoplasmic Reticulum Stress in Rats

Article type: Research Article

Authors: Lin, Li | Yang, Shu-Sheng | Chu, Jiang | Wang, Lu | Ning, Lin-Na | Zhang, Teng | Jiang, Qian | Tian, Qing^{; *} | Wang, Jian-Zhi^{; *}

Affiliations: Department of Pathophysiology, Key Laboratory of Ministry of Education of Neurological Diseases, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

Correspondence: [*] Correspondence to: Dr. Dr. Qing Tian and Dr. Jian-Zhi Wang, Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, 430030 Wuhan, China. Tel.: +86 27 83692625; Fax: +86 27 83692608; E-mail: tianq@mail.hust.edu.cn; Tel./Fax: +86 27 83693883; E-mail: wangjz@mails.tjmu.edu.cn (Dr. Jian-Zhi Wang).

Abstract: Region-specific neurodegeneration was reported in brains of Alzheimer's disease (AD), but the mechanism is not fully understood. Here, we studied the expression of some AD-associated proteins in temporal cortex, frontal cortex, cerebellum, and hippocampus of 4-month-old male Sprague-Dawley rats. Levels of the phosphorylated tau at Thr231, Ser396, and Ser202/Thr205, phosphorylated amyloid-β protein precursor (AβPP) and amyloid-β, synapse-associated proteins glutamate receptors 2, N-methyl-D-aspartic receptors 1 (NR1), NR2A, NR2B, and postsynaptic density protein 95 were much lower in cerebellum, while the levels of total tau, phosphorylated tau at Thr205, Ser214, Ser262, and Ser198/199/202 epitopes, and total AβPP were similar in the four brain regions. As endoplasmic reticulum (ER) stress was reported in the early stage of AD, we injected tunicamycin, an ER stress inducer, into the lateral ventricular of rats and 48 hours later found in the other three brain regions but not cerebellum, increasing of binding immunoglobulin protein with the increased phosphorylation of pancreatic ER kinase, inositol-requiring enzyme 1, and activating transcription factor 6. Simultaneously, levels of phosphorylated tau at all of the above sites were significantly increased with the activation of glycogen synthase kinase-3β in temporal cortex, frontal cortex, and/or hippocampus, but not cerebellum. The synapse-associated proteins, GluR2, PSD95, and synapsin1, were found decreased in the hippocampus after tunicamycin exposure. These data together may partially explain why the AD-like neuropathology, such as formation of neurofibrillary tangles, was rarely detected in cerebellum.

Keywords: Cerebellum, endoplasmic reticulum stress, frontal cortex, hippocampus, synaptic protein, tau, temporal cortex

DOI: 10.3233/JAD-140207

Journal: Journal of Alzheimer's Disease, vol. 41, no. 4, pp. 1149-1163, 2014