Increase in neuropeptide Y activity impairs social behaviour in association with glutamatergic dysregulation in diabetic mice

Abstract

Background and Purpose: Patients with diabetes mellitus are reported to show a raised prevalence of mental disorders, which may be reflected in impaired social interaction. However, the mechanisms underlying such impairment in diabetes are unknown.Experimental Approach: The present study investigated whether social interaction is impaired in diabetic mice and whether central neuropeptide Y (NPY) and glutamatergic function are involved in such impairment.Key Results: In the three-chamber test, social novelty preference, but not sociability, was impaired in streptozotocin (STZ)-induced diabetic mice. The mRNA level of NPY in the hypothalamus was increased in STZ-induced diabetic mice. Injection of the NPY Y 2 receptor agonist NPY 13-36 into naïve mice impaired social novelty preference, but not sociability, and this effect was inhibited by the Y 2 receptor antagonist BIIE 0246. BIIE 0246 also reversed the impairment of social novelty preference in STZ-induced diabetic mice. Similarly, injection of the AMPA receptor agonist AMPA into naïve mice impaired social novelty preference, but not sociability, and this effect was inhibited by the AMPA receptor antagonist NBQX. Impairment of social novelty preference induced by NPY 13-36 was inhibited by NBQX, whereas impairment of social novelty preference induced by AMPA was not inhibited by BIIE 0246. Finally, impairment of social novelty preference in STZ-induced diabetic mice was reversed by NBQX. Conclusion and Implications:These findings suggest that NPY neurons are activated in diabetic mice and that this may impair social novelty preference by promoting glutamatergic function through Y 2 receptors.

The Effects of Repetitive Transcranial Magnetic Stimulation on Cognitive Impairment and the Brain Lipidome in a Cuprizone-Induced Mouse Model of Demyelination

“…In session 3, another unfamiliar mouse (subject 2, also of the same background, age, gender, and weight as the subject mouse) was placed in the previously empty container, and subject 1 was placed in the other chamber. The time spent in each chamber was calculated, and the percentage of interaction time was calculated as the ratio of interaction time with one chamber to the total interaction time with both chambers during the first 5 min of each session ( Ueda et al, 2021 ). The stranger mice (subject 1 and 2) had no encounters with the subject mice prior to testing.…”

Cholinergic transmission from the basal forebrain modulates social memory in male mice

“…Previous studies have established that multiple brain regions, including the hippocampus, medial prefrontal cortex, amygdala and anterior cingulate cortex, are essential for the modulation of social recognition memory (Hitti & Siegelbaum, 2014;Kim et al, 2015; Kogan et al, 2000;Okuyama et al, 2016;Pereira-Caixeta et al, 2018;Rudebeck et al, 2007;Tanimizu et al, 2017) (also see reviews (Bicks et al, 2015;Montagrin et al, 2018). Although the neuropeptides oxytocin, vasopressin and neuropeptide Y are acknowledged as the main regulators of social recognition memory, other neurotransmitter systems, including ACh, norepinephrine, dopamine and serotonin, also participate in the modulation of social memory (Caldwell, 2017;Ueda et al, 2020;van der Kooij & Sandi, 2012). Most studies suggesting that the central cholinergic system contributes to the modulation of social recognition have focused on global ACh level changes (Prado et al, 2006;Riedel et al, 2009;Winslow & Camacho, 1995).…”

High glucose‐mediated VPS26a down‐regulation dysregulates neuronal amyloid precursor protein processing and tau phosphorylation

“…When designing animal experiments, it is critical to take sexes into account (Docherty et al, 2019). However, male mice are practically used in previous diabetes researches (Rahman et al, 2020; Ueda et al, 2021) because the oestrus cycle may affect the experimental conditions and results. Because the aim of our study is to investigate the effects of diabetes on the retromer and related dysregulation of mechanisms of APP processing and tau phosphorylation, male mice were used in the present study.…”