title: Insulin treatment restores glutamate (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor function in the hippocampus of diabetic rats.
abstract: Type 1 diabetes is associated with cognitive dysfunction. Cognitive processing, particularly memory acquisition, depends on the regulated enhancement of expression and function of glutamate receptor subtypes in the hippocampus. Impairment of memory was been detected in rodent models of type 1 diabetes induced by streptozotocin (STZ). This study examines the functional properties of synaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and the expression of synaptic molecules that regulate glutamatergic synaptic transmission in the hippocampus of STZ-diabetic rats. The AMPA receptor-mediated miniature excitatory postsynaptic currents (mEPSCs) and single-channel properties of synaptosomal AMPA receptors were examined after 4 weeks of diabetes induction. Results show that amplitude and frequency of mEPSCs recorded from CA1 pyramidal neurons were decreased in diabetic rats. In addition, the single-channel properties of synaptic AMPA receptors from diabetic rat hippocampi were different from those of controls. These impairments in synaptic currents gated by AMPA receptors were accompanied by decreased protein levels of AMPA receptor subunit GluR1, the presynaptic protein synaptophysin, and the postsynaptic anchor protein postsynaptic density protein 95 in the hippocampus of diabetic rats. Neural cell adhesion molecule (NCAM), an extracellular matrix molecule abundantly expressed in the brain, and the polysialic acid (PSA) attached to NCAM were also downregulated in the hippocampus of diabetic rats. Insulin treatment, when initiated at the onset of diabetes induction, reduced these effects. These findings suggest that STZ-induced diabetes may result in functional deteriorations in glutamatergic synapses in the hippocampus of rats and that these effects may be reduced by insulin treatment.
authors: Department of Biomedical Sciences, College of Veterinary Medicine, Nursing and Allied Health, Tuskegee University, Tuskegee, Alabama.
authors: Nilmini
authors: N
authors: Viswaprakash
authors: Department of Neurobiology and Behavior, Stony Brook University, Stony Brook, New York.|Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, Alabama.
authors: Thirumalini
authors: T
authors: Vaithianathan
authors: Biology Department and Spine Rehabilitation Center, University of Alabama-Birmingham, Birmingham, Alabama.
authors: Ajitan
authors: A
authors: Viswaprakash
authors: Department of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, Alabama.
authors: Robert
authors: R
authors: Judd
authors: Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, Alabama.|Department of Biological and Environmental Sciences, Texas A&M University-Commerce, Commerce, Texas.
authors: Kodeeswaran
authors: K
authors: Parameshwaran
authors: Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, Alabama.
authors: Vishnu
authors: V
authors: Suppiramaniam
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity; D055592:Biophysical Phenomena / Q000187:drug effects; D001786:Blood Glucose / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000178:diet therapy*; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism* / Q000473:pathology; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D066298:In Vitro Techniques; D007328:Insulin / Q000627:therapeutic use*; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D019006:Neural Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000378:metabolism*; D013311:Streptozocin / Q000633:toxicity; D013574:Synaptosomes / Q000378:metabolism
chemical_list: D000903:Antibiotics, Antineoplastic; D001786:Blood Glucose; D018683:Excitatory Amino Acid Agents; D007004:Hypoglycemic Agents; D007328:Insulin; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules; D018091:Receptors, AMPA; D013311:Streptozocin
keywords: AMPA receptors; diabetes; hippocampus; insulin; polysialic acid; synapse