title: Injection of muscimol, a GABAa agonist into the anterior thalamic nucleus, suppresses hippocampal neurogenesis in amygdala-kindled rats.
abstract: The relationship between neurogenesis and epilepsy remains to be solved so far, although aberrant electric circuit recognized in epilepsy might be involved in neurogenesis. In this study, neurogenesis and the proliferation of astrocytes in the subgranular zone of the hippocampus were explored using unilateral amygdala-kindled rats with or without muscimol, a gamma-aminobutyric acid a (GABAa) agonist injection into the bilateral anterior thalamic nuclei (AN). Muscimol injection significantly ameliorated the behavioral scores of epilepsy without any significant alteration on the electroencephalography recorded at the stimulated basolateral amygdala, thus suggesting that muscimol injection might affect the secondary generalization, but not the initial discharge itself. The number of bromodeoxyuridine (BrdU), BrdU/doublecortin and BrdU/glial fibrillary acidic protein-positive cells in the subgranular zone of kindled animals increased markedly. Muscimol injection significantly suppressed neurogenesis, but not the proliferation of astrocyte, in the subgranular zone of the non-stimulated side, probably through the suppression of secondary generalization via AN. The results might indicate the underlying relationships between neurogenesis and epilepsy, that epileptic propagation in unilateral amygdala-kindled rats might go through AN into the contralateral side with subsequent neurogenesis, although further studies need to clarify the hypothesis.
authors.affiliation: Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kuramoto
authors.forename: Takao
authors.initials: T
authors.lastname: Yasuhara
authors.forename: Takashi
authors.initials: T
authors.lastname: Agari
authors.forename: Akihiko
authors.initials: A
authors.lastname: Kondo
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Matsui
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Miyoshi
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Shingo
authors.forename: Isao
authors.initials: I
authors.lastname: Date
mesh_terms: D000679:Amygdala; D000818:Animals; D020643:Anterior Thalamic Nuclei / Q000187:drug effects* / Q000502:physiology; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D004558:Electric Stimulation / Q000009:adverse effects; D004569:Electroencephalography / Q000379:methods; D004827:Epilepsy / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D007839:Functional Laterality; D018755:GABA Agonists / Q000494:pharmacology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000502:physiology*; D007211:Indoles; D007696:Kindling, Neurologic / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009118:Muscimol / Q000494:pharmacology*; D055495:Neurogenesis / Q000187:drug effects*; D009479:Neuropeptides / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C000714848:Dcx protein, rat; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D018755:GABA Agonists; D005904:Glial Fibrillary Acidic Protein; D007211:Indoles; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D009118:Muscimol; C007293:DAPI; D001973:Bromodeoxyuridine