title: Dimethyl fumarate attenuates intracerebroventricular streptozotocin-induced spatial memory impairment and hippocampal neurodegeneration in rats.
abstract: Intracerebroventricular (ICV) injection of streptozotocin (STZ) is a widely-accepted animal model of sporadic Alzheimer's disease (sAD). The present study evaluated the ability of dimethyl fumarate (DMF), an agent with antioxidant and anti-inflammatory properties, to prevent spatial memory impairments and hippocampal neurodegeneration mediated by ICV injection of STZ in 4-month-old rats. Rodent chow containing DMF (0.4%) or standard rodent chow was made available on day 0. Rat body weight and food intake were measured daily for whole the experiment (21days). STZ or vehicle (SHAM) ICV injections were performed on days 2 and 4. Spatial reference and working memory were evaluated using the Morris water maze on days 14-21. Cells containing Fluoro-Jade B (neurodegeneration marker), IL-6, IL-10 were quantified in the hippocampus and choline acetyltransferase (ChAT) in the basal forebrain. The disruption of spatial memory and a high density of hippocampal CA1-3 cells labeled with Fluoro-Jade B or containing IL-6 or IL-10 were observed in the STZ group but not in the STZ+DMF group, as compared to the SHAM or SHAM+DMF groups. STZ vs. STZ+DMF differences were found: worse reference memory acquisition, fewer ChAT-positive neurons in the medial septum (Ch1), more Fluoro-Jade-positive CA1 hippocampal cells in STZ rats. DMF therapy in a rodent model of sAD prevented the disruption of spatial reference and working memory, loss of Ch1 cholinergic cells and hippocampal neurodegeneration as well as the induction of IL-6 and IL-10 in CA1. These beneficial cognitive and molecular effects validate the anti-inflammatory and neuroprotective properties of DMF in the hippocampus.
authors.affiliation: Department of Animal and Human Physiology, Faculty of Biology, University of Gdańsk, Gdańsk, Poland. Electronic address: irena.majkutewicz@biol.ug.edu.pl.
authors.forename: Irena
authors.initials: I
authors.lastname: Majkutewicz
authors.affiliation: Department of Animal and Human Physiology, Faculty of Biology, University of Gdańsk, Gdańsk, Poland.
authors.forename: Ewelina
authors.initials: E
authors.lastname: Kurowska
authors.affiliation: Department of Animal and Human Physiology, Faculty of Biology, University of Gdańsk, Gdańsk, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Podlacha
authors.affiliation: Department of Animal and Human Physiology, Faculty of Biology, University of Gdańsk, Gdańsk, Poland.
authors.forename: Dorota
authors.initials: D
authors.lastname: Myślińska
authors.affiliation: Department of Animal and Human Physiology, Faculty of Biology, University of Gdańsk, Gdańsk, Poland.
authors.forename: Beata
authors.initials: B
authors.lastname: Grembecka
authors.affiliation: Department of Animal and Human Physiology, Faculty of Biology, University of Gdańsk, Gdańsk, Poland.
authors.forename: Jan
authors.initials: J
authors.lastname: Ruciński
authors.affiliation: Department of Animal and Human Physiology, Faculty of Biology, University of Gdańsk, Gdańsk, Poland.
authors.forename: Karolina
authors.initials: K
authors.lastname: Plucińska
authors.affiliation: Department of Animal and Human Physiology, Faculty of Biology, University of Gdańsk, Gdańsk, Poland.
authors.forename: Grażyna
authors.initials: G
authors.lastname: Jerzemowska
authors.affiliation: Department of Animal and Human Physiology, Faculty of Biology, University of Gdańsk, Gdańsk, Poland.
authors.forename: Danuta
authors.initials: D
authors.lastname: Wrona
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D001835:Body Weight / Q000187:drug effects; D002802:Cholinesterases / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D000069462:Dimethyl Fumarate / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004435:Eating / Q000187:drug effects; D005452:Fluoresceins / Q000378:metabolism; D006624:Hippocampus / Q000473:pathology*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007276:Injections, Intraventricular; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy*; D019636:Neurodegenerative Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin / Q000008:administration & dosage
chemical_list: D000903:Antibiotics, Antineoplastic; D016207:Cytokines; D005452:Fluoresceins; D007166:Immunosuppressive Agents; C435731:fluoro jade; D013311:Streptozocin; D002802:Cholinesterases; D000069462:Dimethyl Fumarate
keywords: Alzheimer’s disease; Dimethyl fumarate; Hippocampus; Memory disorder; Neurodegeneration; Spatial; Streptozotocin