Alterations of NR2B and PSD-95 expression in hippocampus of kainic acid-exposed rats with behavioural deficits.
Temporal lobe epilepsy (TLE), characterized by spontaneous recurrent seizure (SRS), is associated with behavioural problems, but the underlying molecular mechanisms have not been clearly identified. In the present study, kainic acid (KA) was administered systemically in adult male Wistar rats to induce SRS. Behavioural performance analyses at 2, 4, and 6 weeks post-status epilepticus (post-SE) showed spatial learning memory deficit, anxiety and increased locomotor activity in rats with long-term SRS compared with rats without SRS after normal saline (NS) or KA-valproate (KA-VPA) treatment. No neuronal cell loss was observed in the hippocampus at 6 weeks post-SE. Reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot analyses revealed that down-regulation of NMDA receptor subunit 2B (NR2B) and postsynaptic density protein-95 (PSD-95) expression in adult hippocampus was found at 4 weeks post-SE and a further decrease at 6 weeks post-SE compared with rats without SRS after NS or KA-VPA treatment. Furthermore, the decreased expression of NR2B and PSD-95 was correlated with the representatively behavioural deficit. These findings suggest that long-term SRS might decrease NR2B/PSD-95 expression in adult hippocampus and consequently cause behavioural deficits, including spatial learning memory deficit, anxiety and increased locomotor activity. Maintaining the expression of NR2B/PSD-95 might partially contribute to the normal behaviour in rats with long-term SRS.
Sun
Qin-Jian
QJ
Department of Neurology, Qianfoshan Hospital, Shandong University, 66 Jingshi Road, Jinan, Shandong 250014, PR China. sqj1210@163.com
Duan
Rui-Sheng
RS
Wang
Ai-Hua
AH
Shang
Wei
W
Zhang
Tao
T
Zhang
Xiu-Qing
XQ
Chi
Zhao-Fu
ZF
D000818:Animals; D000076122:Disks Large Homolog 4 Protein; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced / Q000378:metabolism*; D005106:Exploratory Behavior / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D007608:Kainic Acid; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008565:Membrane Proteins / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013037:Spatial Behavior / Q000502:physiology*; D013226:Status Epilepticus / Q000139:chemically induced / Q000378:metabolism
D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D007608:Kainic Acid