Hippocampal glutamate level and glutamate aspartate transporter (GLAST) are up-regulated in senior rat associated with isoflurane-induced spatial learning/memory impairment.
Postoperative cognitive decline is a clinical concern especially for senior patients. It is generally recognized that glutamatergic system plays a crucial role in the physiopathologic process of neurocognitive deterioration. However, alterations of glutamatergic system in prolonged isoflurane-induced learning/memory decline are still unclear. This study investigates the question whether glutamate concentration and corresponding transporters or receptors display any alternations in aged rat suffering from isoflurane-induced learning/memory impairment. 111 male Sprague-Dawley rats (>18 months) were randomly divided into two main groups: hippocampal microdialysis group (n = 38) and western blotting group (n = 73). Each group was subdivided into three subgroups including (1) control subgroup (n = 6 and 10, receiving no behavioral trial, anesthesia or air exposure); (2) air-exposed subgroup (n = 7 and 15, receiving behavioral trial and air exposure but not anesthesia); (3) isoflurane anesthesia subgroup (n = 25 and 48, receiving both behavioral trial and anesthesia). The isoflurane-exposed rats were further divided into a learning/memory-impaired subgroup and a non-learning/memory-impaired subgroup according to their behavioral performance, which was measured using Morris water maze. Hippocampal glutamate concentrations in microdialysates were determined by high-performance liquid chromatography. Expression levels of GLAST, GLT-1, NMDAR1, NMDAR2A/B, AMPAR and tau in hippocampus were assessed via quantitative Western blotting. The incidences of learning/memory impairment of isoflurane-exposed rats in hippocampal microdialysis group and western blotting group were 12.0 (3/25) and 10.4 % (5/48) respectively. The intra-anesthesia hippocampal glutamate levels were significantly lower than those of non-anesthesized rats. The learning/memory-impaired rats showed a long-lasting increased glutamate level from 24 h after isoflurane exposure to the end of the study, but the other 22 isoflurane-exposed rats did not. The learning/memory-impaired subgroup displayed a significantly higher GLAST level than the other three subgroups (p = 0.026, 0.02 and 0.032 respectively). The expression levels of GLT-1, NMDAR1, NMDAR2A/B and AMPAR of every subgroup were comparable. We found a continuous raised hippocampal glutamate and an up-regulation of GLAST rather than GLT-1, NMDAR1, NMDAR2A/B, AMPAR or tau in hippocampus of aged rats associated with isoflurane-induced learning/memory impairment.
Beijing Chao-yang Hospital, Capital Medical University, Beijing, China.
Xiangdong
X
Qu
Chengshi
C
Xu
Hui
H
Wang
Jie
J
Xu
Weiran
W
Liu
Yun
Y
Wang
Xingyuan
X
Jia
Zhongcong
Z
Xie
Zhipeng
Z
Xu
Chao
C
Ji
Anshi
A
Wu
Yun
Y
Yue
D000375:Aging / Q000502:physiology / Q000523:psychology*; D018685:Anesthetics, Inhalation / Q000633:toxicity*; D000818:Animals; D015153:Blotting, Western; D027341:Excitatory Amino Acid Transporter 1 / Q000096:biosynthesis*; D027342:Excitatory Amino Acid Transporter 2 / Q000096:biosynthesis; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D007530:Isoflurane / Q000633:toxicity*; D007859:Learning Disabilities / Q000139:chemically induced / Q000378:metabolism* / Q000523:psychology; D018782:Maze Learning / Q000187:drug effects*; D008569:Memory Disorders / Q000139:chemically induced / Q000378:metabolism* / Q000523:psychology; D017551:Microdialysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000096:biosynthesis; D016194:Receptors, N-Methyl-D-Aspartate / Q000096:biosynthesis; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D018685:Anesthetics, Inhalation; D027341:Excitatory Amino Acid Transporter 1; D027342:Excitatory Amino Acid Transporter 2; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; C493395:Slc1a2 protein, rat; C493392:Slc1a3 protein, rat; D018698:Glutamic Acid; D007530:Isoflurane