title: Orexin-A-induced ERK1/2 activation reverses impaired spatial learning and memory in pentylenetetrazol-kindled rats via OX1R-mediated hippocampal neurogenesis.
abstract: Epilepsy is characterized by the occurrence of repetitive seizures and can greatly affect a patient's cognition, particularly in terms of learning and memory. Orexin-A is an excitatory neuropeptide produced by the lateral hypothalamus that has been shown to be involved in learning and memory. A reduction in the levels of orexin-A after seizures may underlie the learning and memory impairments induced by epilepsy. Thus, we used pentylenetetrazol (PTZ)-kindled rats to investigate the effects of orexin-A on learning and memory and the involvement of neurogenesis in the dentate gyrus in OX1R-mediated ERK1/2 activation. A Morris water maze test revealed reduced escape latencies, prolonged times in the target quadrant and an increased number of platform crossings in PTZ-kindled rats exposed to orexin-A. These ameliorating effects of orexin-A on spatial learning and memory were attenuated by the intracerebroventricular injection of the OX1R antagonist SB334867 or the ERK1/2 inhibitor U0126. Further studies using bromodeoxyuridine (BrdU) revealed that orexin-A increased the number of BrdU-positive cells, doublecortin (DCX)/BrdU levels and the number of NeuN/BrdU double-positive nuclei in the dentate gyrus of PTZ-kindled rats. However, these effects were inhibited by treatment with SB334867 or U0126. Taken together, these data suggest that orexin-A attenuated the impairment of spatial learning and memory in PTZ-kindled rats and that this attenuation involved neurogenesis in the dentate gyrus via OX1R-mediated ERK1/2 activation.
authors: Department of Neurology, Qianfoshan Hospital, Shandong University, 16766 Jingshi Road, Jinan, Shandong 250014, PR China.
authors: Xuan
authors: X
authors: Zhao
authors: Department of Neurology, Qianfoshan Hospital, Shandong University, 16766 Jingshi Road, Jinan, Shandong 250014, PR China.
authors: Rui xue
authors: Rx
authors: Zhang
authors: Department of Neurology, Qianfoshan Hospital, Shandong University, 16766 Jingshi Road, Jinan, Shandong 250014, PR China.
authors: Shi
authors: S
authors: Tang
authors: Department of Neurology, Qianfoshan Hospital, Shandong University, 16766 Jingshi Road, Jinan, Shandong 250014, PR China.
authors: Yan yan
authors: Yy
authors: Ren
authors: Department of Neurology, Qianfoshan Hospital, Shandong University, 16766 Jingshi Road, Jinan, Shandong 250014, PR China.
authors: Wei xia
authors: Wx
authors: Yang
authors: Department of Neurology, Qianfoshan Hospital, Shandong University, 16766 Jingshi Road, Jinan, Shandong 250014, PR China.
authors: Xiao min
authors: Xm
authors: Liu
authors: Department of Neurology, Qianfoshan Hospital, Shandong University, 16766 Jingshi Road, Jinan, Shandong 250014, PR China. Electronic address: tangjiyou@sohu.com.
authors: Ji you
authors: Jy
authors: Tang
mesh_terms: D000818:Animals; D001583:Benzoxazoles / Q000494:pharmacology; D000089662:Doublecortin Protein; D004789:Enzyme Activation / Q000187:drug effects; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009287:Naphthyridines; D055495:Neurogenesis / Q000187:drug effects*; D009479:Neuropeptides / Q000378:metabolism / Q000494:pharmacology*; D000068796:Orexin Receptor Antagonists; D064446:Orexin Receptors / Q000378:metabolism*; D000068797:Orexins; D010433:Pentylenetetrazole / Q000494:pharmacology*; D017208:Rats, Wistar; D065853:Spatial Learning / Q000187:drug effects*; D014508:Urea / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: C420062:1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea; D001583:Benzoxazoles; C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; C578627:Hcrtr1 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D009287:Naphthyridines; D009479:Neuropeptides; D000068796:Orexin Receptor Antagonists; D064446:Orexin Receptors; D000068797:Orexins; D014508:Urea; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D010433:Pentylenetetrazole
keywords: ERK(1/2); Epilepsy; Learning and memory; Neurogenesis; OX1R; Orexin-A