title: The dendrites of granule cell layer neurons are the primary injury sites in the "Brain Diabetes" rat.
abstract: We previously demonstrated that rats that receive dorsal third ventricle (3V) streptozotocin (STZ) injections (STZ-3V-rats) exhibit cognitive decline as measured by the Morris Water Maze (MWM) and can be used as an animal model of Alzheimer's disease (AD). Immunohistochemical studies of the hippocampal formations of these animals have revealed significant changes in cerebral insulin signalling pathways, as well as marked increases of amyloid beta (Ab) deposition. Here, we performed Sholl analyses of granule cell layer dendrites and measured dendrite spine densities to assess the effect of STZ on hippocampal morphology. In STZ-3V rats as the results, more branching, complex dendrite arborisation, and increased soma size of the granule cells were observed, while spine densities were decreased in all three spine types. An intraventricular injection of a long-acting insulin analogue improved STZ-induced behavioural and immunohistochemical changes. Nevertheless, dendrite spine densities remained diminished, presumably due to overall null changes since new spine formation due to insulin stimulation has been compensated by loss of old spines. It is concluded that cognitive decline in the "Brain Diabetes" rats is primarily due to impaired intracerebral insulin signalling and the ultimate results were injured excitatory inputs through the perforant pathway.
authors.affiliation: Okinaka Memorial Institute for Medical Research, Tokyo, Japan. Electronic address: akisheashin@toranomon.gr.jp.
authors.forename: Akiko Sheala
authors.initials: AS
authors.lastname: Shingo
authors.affiliation: University of South Florida College of Medicine, FL, USA.
authors.forename: Ronald F
authors.initials: RF
authors.lastname: Mervis
authors.affiliation: Biopathology Institute, Ohita, Japan.
authors.forename: Tomomichi
authors.initials: T
authors.lastname: Kanabayashi
authors.affiliation: Chigasaki Tokushu-kai Clinic, Kanagawa, Japan.
authors.forename: Shozo
authors.initials: S
authors.lastname: Kito
authors.affiliation: Okinaka Memorial Institute for Medical Research, Tokyo, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Murase
mesh_terms: D000818:Animals; D048429:Cell Size / Q000187:drug effects; D003712:Dendrites / Q000187:drug effects / Q000473:pathology* / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D007150:Immunohistochemistry; D007276:Injections, Intraventricular; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D017208:Rats, Wistar; D013311:Streptozocin
chemical_list: D013311:Streptozocin
keywords: Dendritic spine; Dentate gyrus; Insulin; Streptozotocin