title: Increased mu-opioid receptor labeling is found on inner molecular layer terminals of the dentate gyrus following seizures.
abstract: The hippocampal formation is a brain region sensitive to seizure development, a phenomenon thought to be mediated in part by mu-opioid receptor (MOR) activation. Previous studies have found a delayed increase in MOR immunoreactivity (IR) in the inner molecular layer (IML) of the dentate gyrus after experimentally induced seizures. However, whether these increases in MOR-IR are restricted to certain cell types or cellular compartments (i.e., presynaptic, postsynaptic, or glial profiles) has not been determined. Thus, the present study examined which subcellular profiles demonstrate changes in MOR-IR after kainic acid (KA)-induced seizures. Light microscopic (LM) analysis demonstrated seizure-induced increases in MOR-IR at three points of the IML (dorsal blade, ventral blade, and crest) at three levels of section (septal, mid-septotemporal, and temporal). Electron microscopic analysis of the IML revealed that MOR-IR was present in the same types of cellular profiles in both control and KA-treated rats. However, a significant increase in the number of MOR-labeled terminal profiles was revealed in KA-treated rats compared to controls. Additionally, some MOR-labeled terminals in KA-treated rats possessed excitatory-type morphology and contained enkephalin or dynorphin, peptides found in mossy fiber terminals. These data suggest that most of the seizure-induced increases in MOR expression in the IML are associated with terminals originating from several different neuronal populations, including granule cells, and possibly, surviving GABAergic interneurons, septal cholinergic, and/or supramamillary projection neurons.
authors.affiliation: Division of Neurobiology, Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, NY 10021, USA.
authors.forename: P S
authors.initials: PS
authors.lastname: Skyers
authors.forename: S
authors.initials: S
authors.lastname: Einheber
authors.forename: J P
authors.initials: JP
authors.lastname: Pierce
authors.forename: T A
authors.initials: TA
authors.lastname: Milner
mesh_terms: D000818:Animals; D003712:Dendrites / Q000648:ultrastructure; D018891:Dentate Gyrus / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D004745:Enkephalins / Q000096:biosynthesis; D007150:Immunohistochemistry; D007608:Kainic Acid; D008297:Male; D019599:Mossy Fibers, Hippocampal / Q000378:metabolism / Q000648:ultrastructure; D017729:Presynaptic Terminals / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000378:metabolism*; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology
chemical_list: D004745:Enkephalins; D017450:Receptors, Opioid, mu; D007608:Kainic Acid