title: Synaptotagmin I hypothalamic knockdown prevents amygdaloid seizure-induced damage of hippocampal neurons but not of entorhinal neurons.
abstract: We have previously demonstrated that an acute pharmacological interruption of the afferent inputs from the hypothalamus to the hippocampus resulted in the blockade of the genesis and spread of intra-amygdala kainate-induced seizure activity in the hippocampus. This finding suggests that a sustained interruption of the hypothalamic stimulative influences may completely prevent amygdaloid seizure-induced hippocampal neuron damage. To test this assumption, we delivered antisense oligodeoxynucleotides (ODNs) against synaptotagmin I, a regulatory protein of the transmitter release machinery, into the hypothalamus by using a Hemagglutinating virus of Japan (HVJ)-liposome-mediated gene transfer technique. Four days prior to the induction of status epilepticus by intra-amygdala injection of kainate, the synaptotagmin I antisense was injected into the supramammillary nucleus (SuM) of the hypothalamus to chronically suppress the stimulative influences to the hippocampus via the reduction of transmitter release. The synaptotagmin I hypothalamic knockdown resulted in the almost complete prevention of seizure-induced damage of hippocampal neurons but not of entorhinal neurons following the kainate-induced amygdaloid seizures. This result suggests that the hypothalamic stimulative influences to the hippocampus have a major contribution to the amygdaloid seizure-induced hippocampal sclerosis, probably via disinhibition mechanism.
authors.affiliation: Department of Physiology, School of Allied Health Sciences, Kitasato University, Sagamihara, Kanagawa 228-8555, Japan. shizuka@ahs.kitasato-u.ac.jp
authors.forename: Shizuka
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Kousaku
authors.initials: K
authors.lastname: Ohno
authors.forename: Miwa
authors.initials: M
authors.lastname: Iwakuma
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Kaneda
authors.forename: Makoto
authors.initials: M
authors.lastname: Saji
mesh_terms: D000679:Amygdala / Q000503:physiopathology; D000818:Animals; D002135:Calcium-Binding Proteins; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D018728:Entorhinal Cortex / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D004833:Epilepsy, Temporal Lobe / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D007031:Hypothalamus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007608:Kainic Acid; D008297:Male; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009434:Neural Pathways / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D050863:Synaptotagmin I; D050857:Synaptotagmins
chemical_list: D002135:Calcium-Binding Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D016376:Oligonucleotides, Antisense; D050863:Synaptotagmin I; C494312:Syt1 protein, rat; D050857:Synaptotagmins; D007608:Kainic Acid