Functional Integration of Adult-Generated Neurons in Diabetic Goto-Kakizaki Rats.

Chelsey C Damphousse,Jaclyn Medeiros,Diano F Marrone

doi:10.3389/fnbeh.2021.734359

Chelsey C Damphousse, Jaclyn Medeiros + Show 1 more

Open Access

https://doi.org/10.3389/fnbeh.2021.734359

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Abstract

Adult-born neurons in the dentate gyrus (DG) make important contributions to learning as they integrate into neuronal networks. Neurogenesis is dramatically reduced by a number of conditions associated with cognitive impairment, including type 2 diabetes mellitus (T2DM). Increasing neurogenesis may thus provide a therapeutic target for ameliorating diabetes-associated cognitive impairments, but only if new neurons remain capable of normal function. To address the capacity for adult-generated neurons to incorporate into functional circuits in the hyperglycemic DG, we measured Egr1 expression in granule cells (GCs), BrdU labeled four weeks prior, in Goto-Kakizaki (GK) rats, an established model of T2DM, and age-matched Wistars. The results indicate that while fewer GCs are generated in the DG of GK rats, GCs that survive readily express Egr1 in response to spatial information. These data demonstrate that adult-generated GCs in the hyperglycemic DG remain functionally competent and support neurogenesis as a viable therapeutic target.

Highlights

Type 2 diabetes mellitus (T2DM) has long been associated with cognitive impairment and an increased risk of dementia
The results indicate that while fewer granule cells (GCs) are generated in the dentate gyrus (DG) of GK rats, GCs that survive readily express early growth response 1 (Egr1) in response to spatial information
Consistent with previous data, the current study shows that GK rats display a deficit in spatial memory that is correlated with decreased survival of adult-generated granule cells (agGCs)

Summary

Introduction

Type 2 diabetes mellitus (T2DM) has long been associated with cognitive impairment and an increased risk of dementia. Clarifying the neuronal changes that drive DACD may be aided through the use of animal models such as the Goto-Kakizaki (GK) rat (Goto et al, 1975; Kimura et al, 1982), a strain selectively bred for insulin resistance and persistent hyperglycemia in the absence of obesity These animals display cognitive deficits (e.g., Matsunaga et al, 2016; Li et al, 2017; Tian et al, 2018; Yang et al, 2018) comparable to those exhibited by humans with T2DM (e.g., Biessels et al, 2006; Lu et al, 2009; Cukierman-Yaffe, 2014; Palta et al, 2014; Moheet et al, 2015)

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