Region-specific expression of tau, amyloid-β protein precursor, and synaptic proteins at physiological condition or under endoplasmic reticulum stress in rats.
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.
Department of Pathophysiology, Key Laboratory of Ministry of Education of Neurological Diseases, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Li
L
Lin
Department of Pathophysiology, Key Laboratory of Ministry of Education of Neurological Diseases, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Shu-Sheng
SS
Yang
Department of Pathophysiology, Key Laboratory of Ministry of Education of Neurological Diseases, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Jiang
J
Chu
Department of Pathophysiology, Key Laboratory of Ministry of Education of Neurological Diseases, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Lu
L
Wang
Department of Pathophysiology, Key Laboratory of Ministry of Education of Neurological Diseases, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Lin-Na
LN
Ning
Department of Pathophysiology, Key Laboratory of Ministry of Education of Neurological Diseases, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Teng
T
Zhang
Department of Pathophysiology, Key Laboratory of Ministry of Education of Neurological Diseases, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Qian
Q
Jiang
Department of Pathophysiology, Key Laboratory of Ministry of Education of Neurological Diseases, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Qing
Q
Tian
Department of Pathophysiology, Key Laboratory of Ministry of Education of Neurological Diseases, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Jian-Zhi
JZ
Wang
D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D000076122:Disks Large Homolog 4 Protein; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*; D016704:Synapsins / Q000378:metabolism; D014415:Tunicamycin / Q000494:pharmacology; D016875:tau Proteins / Q000378:metabolism*
D016564:Amyloid beta-Protein Precursor; D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D017470:Receptors, Glutamate; D016704:Synapsins; D016875:tau Proteins; D014415:Tunicamycin
Cerebellum; endoplasmic reticulum stress; frontal cortex; hippocampus; synaptic protein; tau; temporal cortex