title: NMDA receptor NR2B subunits contribute to PTZ-kindling-induced hippocampal astrocytosis and oxidative stress.
abstract: The N-methyl-d-aspartate (NMDA) receptor plays an important role in the pathophysiology of several neurological diseases, including epilepsy. The present study investigated the effect of NMDA receptor NR2B subunits on pentylenetetrazole (PTZ)-kindling-induced pathological and biochemical events in mice. Our results showed that PTZ-kindling up-regulates the expression of NMDA receptor NR2B subunits in the hippocampus and that kindled mice were characterized by significant astrocytosis and neuron loss in the hippocampus. Oxidative stress, including excessive malondialdehyde (MDA) production and decreased enzymatic activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX), were detected in the hippocampus after the mice were fully kindled. Additionally, expression of brain-derived neurotrophic factor (BDNF) in the hippocampus was found to be up-regulated in PTZ-kindled mice. However, selectively blocking NMDA receptor NR2B subunits by ifenprodil significantly suppressed PTZ-kindling-induced hippocampal astrocytosis, oxidative stress and neuron loss. Furthermore, blocking NMDA receptor NR2B subunits also abolished PTZ-kindling-induced BDNF expression. These results indicate that NMDA receptor NR2B subunits contribute to epilepsy-associated pathological and biochemical events, including hippocampal astrocytosis, oxidative stress and neuron loss, and these events might be correlated with up-regulation of BDNF expression.
authors.affiliation: Department of Pharmacology, Medical School of Southeast University, Nanjing, China. Electronic address: xinjianzhu@seu.edu.cn.
authors.forename: Xinjian
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Neurology, Nanjing Brain Hospital, Nanjing, China.
authors.forename: Jingde
authors.initials: J
authors.lastname: Dong
authors.affiliation: Department of Pharmacology, Medical School of Southeast University, Nanjing, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Shen
authors.affiliation: Department of Pharmacology, Medical School of Southeast University, Nanjing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Bai
authors.affiliation: Department of Pharmacology, Medical School of Southeast University, Nanjing, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Medical School of Southeast University, Nanjing, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Lv
authors.affiliation: Department of Physiology, Medical School of Southeast University, Nanjing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Chao
authors.affiliation: Department of Pharmacology, Medical School of Southeast University, Nanjing, China.
authors.forename: Honghong
authors.initials: H
authors.lastname: Yao
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D004827:Epilepsy / Q000378:metabolism; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005911:Gliosis / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D005979:Glutathione Peroxidase / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D007696:Kindling, Neurologic / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D010433:Pentylenetetrazole; D010880:Piperidines / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D018691:Excitatory Amino Acid Antagonists; C121001:NR2B NMDA receptor; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D008315:Malondialdehyde; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; C010739:ifenprodil; D010433:Pentylenetetrazole
keywords: Astrocytosis; BDNF; Epilepsy; Kindling; NMDA receptor