title: Spastin in the human and mouse central nervous system with special reference to its expression in the hippocampus of mouse pilocarpine model of status epilepticus and temporal lobe epilepsy.
abstract: In the present in situ hybridization and immunocytochemical studies in the mouse central nervous system (CNS), a strong expression of spastin mRNA and protein was found in Purkinje cells and dentate nucleus in the cerebellum, in hippocampal principal cells and hilar neurons, in amygdala, substantia nigra, striatum, in the motor nuclei of the cranial nerves and in different layers of the cerebral cortex except piriform and entorhinal cortices where only neurons in layer II were strongly stained. Spastin protein and mRNA were weakly expressed in most of the thalamic nuclei. In selected human brain regions such as the cerebral cortex, cerebellum, hippocampus, amygdala, substania nigra and striatum, similar results were obtained. Electron microscopy showed spastin immunopositive staining in the cytoplasma, dendrites, axon terminals and nucleus. In the mouse pilocarpine model of status epilepticus and subsequent temporal lobe epilepsy, spastin expression disappeared in hilar neurons as early as at 2h during pilocarpine induced status epilepticus, and never recovered. At 7 days and 2 months after pilocarpine induced status epilepticus, spastin expression was down-regulated in granule cells in the dentate gyrus, but induced expression was found in reactive astrocytes. The demonstration of widespread distribution of spastin in functionally different brain regions in the present study may provide neuroanatomical basis to explain why different neurological, psychological disorders and cognitive impairment occur in patients with spastin mutation. Down-regulation or loss of spastin expression in hilar neurons may be related to their degeneration and may therefore initiate epileptogenetic events, leading to temporal lobe epilepsy.
authors.affiliation: Epilepsy Research Laboratory, National Neuroscience Institute, Singapore 308433, Singapore.
authors.forename: Dong Liang
authors.initials: DL
authors.lastname: Ma
authors.forename: Shwn Chin
authors.initials: SC
authors.lastname: Chia
authors.forename: Yong Cheng
authors.initials: YC
authors.lastname: Tang
authors.forename: May Ling Joyce
authors.initials: ML
authors.lastname: Chang
authors.forename: Alphonse
authors.initials: A
authors.lastname: Probst
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Burgunder
authors.forename: Feng Ru
authors.initials: FR
authors.lastname: Tang
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000648:ultrastructure; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism*; D003292:Convulsants; D018891:Dentate Gyrus / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004827:Epilepsy / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D004833:Epilepsy, Temporal Lobe / Q000378:metabolism* / Q000503:physiopathology; D005911:Gliosis / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D008297:Male; D051379:Mice; D046529:Microscopy, Electron, Transmission; D018721:Muscarinic Agonists; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure; D010862:Pilocarpine; D012333:RNA, Messenger / Q000378:metabolism; D000074181:Spastin; D013045:Species Specificity; D013226:Status Epilepticus / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D003292:Convulsants; D018721:Muscarinic Agonists; D012333:RNA, Messenger; D010862:Pilocarpine; D000251:Adenosine Triphosphatases; D000074181:Spastin; C498515:Spast protein, mouse