Impaired exploration induced by type 1 diabetes is related to locomotor activity rather than a reduction in motivation

• Published in: Neuroscience 2024-11, Vol.560, p.1-10
• Main Authors: Amorim de Souza Lima, Thiago, Raissa Ribeiro, Martina, Carneiro de Brito, Malcon, Mitiko Kawamoto, Elisa
• Format: Article
• Language: English
• Subjects: Learning and memory; Motivation; Streptozotocin; TNFR1; Type 1 diabetes
• ISSN: 0306-4522; 1873-7544; 1873-7544
• DOI: 10.1016/j.neuroscience.2024.09.030

•Type 1 diabetes reduces exploration without reducing novelty-seeking motivation.•Deletion of TNFR1 attenuates the reduction in gait speed induced by type 1 diabetes.•Type 1 diabetes induces anxiety-like behavior in the first week post-streptozotocin.•Deletion of TNFR1 induces working memory impairment in normoglycemic mice. Type 1 diabetes mellitus (T1D) is associated with cognitive impairments in humans. A well-established animal model of T1D is induced through the administration of streptozotocin (STZ), a glucose analog that induces pancreatic β-cell death, resulting in hyperglycemia and cognitive impairment linked to neuroinflammation and oxidative stress. Tumor necrosis factor (TNF)-α, a key inflammatory mediator, is elevated in the central nervous system (CNS) of diabetic animals. In this study, we utilized TNFR1 knockout mice to investigate the role of TNFR1 signaling in short-term T1D-related cognitive impairment. Our findings showed that diabetic animals did not develop cognitive damage within the first 2 weeks of T1D but exhibited reduced exploration in all behavioral tests. Our findings suggest that this reduction in exploration was attributable to motor impairment, as there was no reduction in motivated novelty-seeking behavior. Additionally, deletion of TNFR1 signaling attenuated gait speed impairment in diabetic mice, but did not affect other motor-related or exploratory behaviors.