Evidence for cortical neuronal loss in male type 2 diabetic Goto-Kakizaki rats

J Alzheimers Dis. 2014;41(2):551-60. doi: 10.3233/JAD-131958.


Type 2 diabetes (T2D) is strongly associated with early cognitive decline and may facilitate the development of neurodegenerative diseases. Despite the overwhelming amount of indirect evidence pointing toward the presence of cerebral neurodegeneration in T2D, no hard proof of it on histological and quantitative levels exists. This warrants more research to investigate whether T2D can lead to neurodegeneration in the central nervous system and to study the precise nature and temporal dynamics of such changes. We performed a comprehensive quantitative assessment of T2D-induced changes in neuronal and glial numbers in the cerebral cortex using stereological methods. We compared the cellular composition of 3- and 13-month-old male type 2 diabetic Goto-Kakizaki (GK) rat brains. Age and sex-matched Wistar rats served as healthy controls. Our results show a significant decrease in neuron numbers (≈11%) in the cerebral cortex of 13-month-old GK rats compared to young, or Wistar rats, while astroglia numbers were unchanged. We also recorded increased microglia activation in aged diabetic rat brains as indicated by significantly increased average microglia cell volume. Our observations provide quantitative evidence of T2D-induced changes in brain's cellular composition during aging. These findings may facilitate the mechanistic understanding of cognitive dysfunction and other neurodegenerative disorders in T2D.

Keywords: Aging; GK rat; cerebral cortex; diabetes; neurodegeneration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / pathology
  • Animals
  • Astrocytes / pathology
  • Blood Chemical Analysis
  • Blood Glucose
  • Cell Count
  • Cell Size
  • Cerebral Cortex / pathology*
  • Diabetes Mellitus, Experimental / pathology*
  • Diabetes Mellitus, Experimental / physiopathology
  • Disease Models, Animal
  • Immunohistochemistry
  • Insulin / blood
  • Male
  • Microglia / pathology
  • Microscopy, Confocal
  • Neurons / pathology*
  • Organ Size
  • Rats, Wistar


  • Blood Glucose
  • Insulin