Enriched environment induces beneficial effects on memory deficits and microglial activation in the hippocampus of type 1 diabetic rats

Metab Brain Dis. 2014 Mar;29(1):93-104. doi: 10.1007/s11011-013-9467-2. Epub 2013 Dec 10.

Abstract

Type 1 diabetes mellitus (T1DM) has been associated with long-term complications in the central nervous system, causing brain cellular dysfunctions and cognitive deficits. On the other hand, enriched environment (EE) induces experience-dependent plasticity, especially in the hippocampus, improving the performance of animals in learning and memory tasks. Thus, our objective was to investigate the influence of the EE on memory deficits, locomotion, corticosterone levels, synaptophysin (SYP) protein immunoreactivity, cell survival and microglial activation in the dentate gyrus (DG) of T1DM rat hippocampus. Male Wistar rats (21-day-old) were exposed to EE or maintained in standard housing (controls, C) for 3 months. At adulthood, the C and EE animals were randomly divided and diabetes was induced in half of them. All the animals received 4 doses of BrdU, 24 h apart. Hippocampus-dependent spatial memory, general locomotion and serum corticosterone levels were evaluated at the end of the experiment. The animals were transcardially perfused 30 days post-BrdU administration. Our results showed that EE was able to prevent/delay the development of memory deficits caused by diabetes in rats, however it did not revert the motor impairment observed in the diabetic group. SYP immunoreactivity was increased in the enriched healthy group. The EE decreased the serum corticosterone levels in diabetic adult rats and attenuated the injurious microglial activation, though without altering the decrease of the survival cell. Thus, EE was shown to help to ameliorate cognitive comorbidities associated with T1DM, possibly by reducing hyperactivity in the hypothalamic-pituitary-adrenal axis and microglial activation in diabetic animals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose / analysis
  • Brain / immunology
  • Brain / metabolism
  • Brain / physiopathology
  • Calcium-Binding Proteins / analysis
  • Corticosterone / blood
  • DNA Replication
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / immunology
  • Diabetes Mellitus, Experimental / psychology*
  • Environment*
  • Exploratory Behavior
  • Hippocampus / immunology
  • Hippocampus / metabolism
  • Hippocampus / physiopathology*
  • Housing, Animal
  • Male
  • Memory Disorders / blood
  • Memory Disorders / etiology
  • Memory Disorders / prevention & control*
  • Microfilament Proteins / analysis
  • Microglia / immunology*
  • Motor Activity
  • Neurogenesis
  • Random Allocation
  • Rats
  • Rats, Wistar
  • Recognition, Psychology
  • Single-Blind Method
  • Spatial Learning
  • Streptozocin
  • Synaptophysin / analysis

Substances

  • Aif1 protein, rat
  • Blood Glucose
  • Calcium-Binding Proteins
  • Microfilament Proteins
  • Synaptophysin
  • Syp protein, rat
  • Streptozocin
  • Corticosterone