title: Somatostatin receptor type 2 undergoes plastic changes in the human epileptic dentate gyrus.
abstract: Temporal lobe epilepsy (TLE) is characterized by hippocampal sclerosis together with profound losses and phenotypic changes of different classes of interneurons, including those expressing somatostatin (SRIF). To understand the functional significance of the plasticity of SRIF transmission in TLE, unraveling the status of SRIF receptors is, however, a prerequisite. To address this issue, we characterized expression and distribution of the major SRIF receptor, the sst2 subtype, in hippocampal tissue resected in patients with TLE using complementary neuroanatomic approaches. In patients with hippocampal sclerosis, the number of cells expressing sst2 receptor mRNA as well as sst2 receptor-binding sites and immunoreactivity decreased significantly in the CA1-3, reflecting neuronal loss. By contrast, in the dentate gyrus, sst2 receptor mRNA expression was strongly increased in the granule cell layer, and sst2 receptor-binding sites and immunoreactivity was preserved in the inner but decreased significantly in the outer molecular layer. In this latter region, pronounced changes in SRIF terminal fields were observed. Decreased receptor density in the distal dendrites of granule cells is likely to reflect downregulation of sst2 receptors in response to physiopathologic release of SRIF. Because sst2 receptors have anticonvulsant and antiepileptogenic properties, this phenomenon may contribute to the etiology of TLE seizures.
authors.affiliation: Neuroendocrine Research Laboratory, Hungarian Academy of Sciences and Department of Human Morphology and Developmental Biology, Semmelweis University, Budapest.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Csaba
authors.forename: Susanne
authors.initials: S
authors.lastname: Pirker
authors.forename: Benjamin
authors.initials: B
authors.lastname: Lelouvier
authors.forename: Axelle
authors.initials: A
authors.lastname: Simon
authors.forename: Catherine
authors.initials: C
authors.lastname: Videau
authors.forename: Jacques
authors.initials: J
authors.lastname: Epelbaum
authors.forename: Thomas
authors.initials: T
authors.lastname: Czech
authors.forename: Christoph
authors.initials: C
authors.lastname: Baumgartner
authors.forename: Günther
authors.initials: G
authors.lastname: Sperk
authors.forename: Pascal
authors.initials: P
authors.lastname: Dournaud
mesh_terms: D000293:Adolescent; D000328:Adult; D001345:Autoradiography / Q000379:methods; D002648:Child; D002675:Child, Preschool; D004833:Epilepsy, Temporal Lobe / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D008297:Male; D008875:Middle Aged; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000378:metabolism*; D015282:Octreotide / Q000493:pharmacokinetics; D011180:Postmortem Changes; D011485:Protein Binding / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D017481:Receptors, Somatostatin / Q000235:genetics / Q000378:metabolism*; D013004:Somatostatin / Q000378:metabolism; D013223:Statistics as Topic
chemical_list: D012333:RNA, Messenger; D017481:Receptors, Somatostatin; D013004:Somatostatin; C093733:somatostatin receptor 2; D015282:Octreotide