Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Cognitive Performance during the Development of Diabetes in the Zucker Diabetic Fatty Rat

Marcia Spoelder
* ORCID logo ,
Yami Bright
,
Martine C. Morrison
ORCID logo ,
Veerle Van Kempen
,
Lilian De Groodt
,
Malvina Begalli
,
Nikita Schuijt
,
Eva Kruiger
,
Ronald Bulthuis
,
Gabriele Gross
,
Robert Kleemann
ORCID logo ,
Janna Van Diepen
ORCID logo ,
Judith R. Homberg
ORCID logo
Version 1 : Received: 28 August 2023 / Approved: 29 August 2023 / Online: 30 August 2023 (03:29:31 CEST)

A peer-reviewed article of this Preprint also exists.

Spoelder, M.; Bright, Y.; Morrison, M.C.; van Kempen, V.; de Groodt, L.; Begalli, M.; Schuijt, N.; Kruiger, E.; Bulthuis, R.; Gross, G.; Kleemann, R.; van Diepen, J.A.; Homberg, J.R. Cognitive Performance during the Development of Diabetes in the Zucker Diabetic Fatty Rat. Cells 2023, 12, 2463. Spoelder, M.; Bright, Y.; Morrison, M.C.; van Kempen, V.; de Groodt, L.; Begalli, M.; Schuijt, N.; Kruiger, E.; Bulthuis, R.; Gross, G.; Kleemann, R.; van Diepen, J.A.; Homberg, J.R. Cognitive Performance during the Development of Diabetes in the Zucker Diabetic Fatty Rat. Cells 2023, 12, 2463.

Abstract

Increased insulin levels may support the development of neural circuits involved in cognition, while chronic mild inflammation may also result in cognitive impairment. This study aimed to gain more insight into whether cognition is impacted already during adolescence in a genetic rat model for obesity and type 2 diabetes. Cognitive functioning throughout adolescence and early adulthood was investigated in Zucker Diabetic Fatty (ZDF), ZDF lean and healthy outbred Long Evans rats using operant touchscreens. Blood glucose, insulin and lipids were longitudinally analyzed. Histological analyses were performed in the liver, white adipose tissues and the prefrontal cortex. Adolescent ZDF obese rats outperformed lean rats on visual discrimination performance. During the longitudinal cognitive testing period, insulin levels sharply increased over weeks in ZDF obese rats and were significantly enhanced from 6 weeks of age onwards. Early signs of liver steatosis and enlarged adipocytes in white adipose tissue were observed in ZDF early adult obese rats. Histological analyses at early adulthood showed no group differences in the number of prefrontal cortex neurons and microglia, nor PSD95 and SIRT1 mRNA expression levels. Together, our data show that adolescent obese ZDF rats even display enhanced cognition despite their early diabetic profile.

Keywords

diabetes; adolescence; cognition; insulin; inflammation

Subject

Biology and Life Sciences, Neuroscience and Neurology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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