Reduced Hippocampal Cell Differentiation in the Subgranular Zone of the Dentate Gyrus in a Rat Model of Type II Diabetes

Abstract

It has recently been reported that diabetes mellitus is strongly associated with neurodegenerative and functional disorders of the central nervous system. In the present study, we investigated the changes in proliferating neurons in the dentate gyrus of type II diabetic rats using doublecortin (DCX), a marker of progenitors differentiating into neurons. At 4 weeks after birth, there were no differences in the blood glucose levels of Zucker diabetic fatty (ZDF) rats or Zucker lean control (ZLC) rats. DCX-immunoreactive neurons were detectable in the subgranular zone of the dentate gyrus in both the ZDF and ZLC rats; however, DCX immunoreactivity was higher in the ZLC rats than in the ZDF rats. At 12 weeks after birth, the blood glucose level was significantly increased by 400 mg/dl in the ZDF rats, but the blood glucose level in the ZLC rats was only slightly increased by 152.3 mg/dl. DCX immunoreactivity was significantly decreased in 12-week-old rats in comparison to 4-week-old rats. Some DCX-immunoreactive neurons were detectable in the subgranular zone of the dentate gyrus in the ZLC rats. However, only a few DCX-immunoreactive neurons were observed in the ZDF rats, and the DCX-immunoreactive neurons in the ZDF rats did not show fully developed processes. These results suggest that DCX-immunoreactive neurons were significantly decreased in an age-dependent manner and that DCX-immunoreactive neurons were also reduced in diabetic rats. In addition, the reduction in DCX-immunoreactive neurons in age matched rats may be associated with type II diabetes.

Alterations of the Giant Pyramidal Neurons (Betz Cells) in Brain Cortex of Rat Offspring Born from Gestational Diabetic Dams: A Morphometric Study

“…Also, several studies have reported reduction of neuronal density in dentate gyrus of animals with type 1 and 2 diabetes mellitus (Hwang et al, 2008;Kim et al, 2003;Li et al, 2002).…”

Neuronal differentiation and developmental characteristics in the dentate gyrus of staggerer mutant mice

“…The marker for neuronal proliferation, differentiation and migration, development, Ki67, doublecortin (DCX), NeuN were used for clarifying the neuronal proliferation, neurogenesis and development of hippocampus in this study. Especially, it has been recently reported that DCX is expressed in differentiated neurons (15), suggesting a role for DCX in neuronal plasticity, axonal outgrowth, or synaptogenesis (16,17). In this study, we used Ki67 to find a neuronal proliferation, DCX to find a neuronal differentiation and NeuN to find mature neuron in the subgranular zone of the DG.…”

Differential Effects of Treadmill Exercise on Calretinin Immunoreactivity in Type 2 Diabetic Rats in Early and Chronic Diabetic Stages

“…Genotyping of Leprfa gene and experimental design: Genotype of Lepr fa gene herein was determined with the strategy described in our previous study [16]. For effects of exercise on CR immunoreactivity at early and chronic stages, 20 male ZLC and ZDF rats in each were randomly divided into 4 groups (n=5 per group) as reported previously [17]: sedentary ZLC (Co-ZLC), sedentary ZDF (Co-ZDF), exercised ZLC (Ex-ZLC) and exercised ZDF (Ex-ZDF).…”

“…Chronic T2DM leads to cognitive impairment [3,11,28,35], a reduction in brain hippocampal volume [12], dementia, and an increase in the risk for Alzheimer's Disease [39,47]. In addition, it has been reported that diabetes negatively affects hippocampal cell proliferation, differentiation, and neurogenesis [16,22,36]. Many studies have reported that exercise causes an increase in learning, cognitive function, and neurogenesis in the dentate gyrus (DG) [33,42,43].…”