{"title":"Impact of feeding age on cognitive impairment in mice with Disrupted-In-Schizophrenia 1 (Disc1) mutation under a high sucrose diet","authors":"Jonghyuk Park , Hiroko Shimbo , Shoko Tamura , Toshifumi Tomoda , Takatoshi Hikida , Haruo Okado , Shinobu Hirai","doi":"10.1016/j.bbr.2024.115291","DOIUrl":null,"url":null,"abstract":"<div><div>A combination of genetic predisposition and environmental factors contributes to the development of psychiatric disorders such as schizophrenia, bipolar disorder and major depressive disorder. Previous studies using mouse models suggested that prolonged high sucrose intake during puberty can serve as an environmental risk factor for the onset of psychiatric disorders. However, the impact of both the duration and timing of high sucrose consumption during different developmental stages on pathogenesis remains poorly defined. We therefore investigated the effects of a long-term high sucrose diet on cognitive deficit, a core symptom of psychiatric disorders, using <em>Disrupted-in-Schizophrenia 1</em> locus-impairment heterozygous mutant (<em>Disc1</em><sup><em>het</em></sup>) mice as a model for genetic predisposition. First, <em>Disc1</em><sup><em>het</em></sup> mice and their littermate control (WT) were fed either a high sucrose diet or a control starch diet for nine weeks starting at weaning (postnatal day 24), and tested for cognitive performance in the object location test (OLT) and the novel object recognition test (NORT) (assessing spatial and recognition memory, respectively). Only <em>Disc1</em><sup><em>het</em></sup> mice on a high sucrose diet displayed deficits in OLT (p < 0.0001), demonstrating impaired hippocampus-dependent spatial memory. This behavioral abnormality was accompanied by a decreased proportion of the high parvalbumin-expressing interneurons (High-PV neurons) in the ventral hippocampus, a cell type that regulates neural activity and a variety of learning and memory processes such as spatial and working memory. We further explored the critical developmental period for high sucrose intake to cause cognitive deficits in adulthood by comparing specific feeding periods during puberty (P24-P65) and post-puberty (P65-P90). Compared to those on a standard chow diet, high sucrose intake caused deficits in spatial memory in both WT and <em>Disc1</em><sup><em>het</em></sup> mice, with more pronounced effects in <em>Disc1</em><sup>het</sup> mice. In particular, <em>Disc1</em><sup><em>het</em></sup> mice on a sucrose diet during adolescence showed more pronounced cognitive deficit than those fed after adolescence. Our results suggest that adolescence is particularly vulnerable to nutritional environmental risk factors, and that high sucrose consumption may cause hippocampus-dependent memory deficits via decreased High-PV interneuron function when combined with Disc1-related genetic predisposition.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"476 ","pages":"Article 115291"},"PeriodicalIF":2.6000,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Behavioural Brain Research","FirstCategoryId":"102","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0166432824004479","RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BEHAVIORAL SCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
A combination of genetic predisposition and environmental factors contributes to the development of psychiatric disorders such as schizophrenia, bipolar disorder and major depressive disorder. Previous studies using mouse models suggested that prolonged high sucrose intake during puberty can serve as an environmental risk factor for the onset of psychiatric disorders. However, the impact of both the duration and timing of high sucrose consumption during different developmental stages on pathogenesis remains poorly defined. We therefore investigated the effects of a long-term high sucrose diet on cognitive deficit, a core symptom of psychiatric disorders, using Disrupted-in-Schizophrenia 1 locus-impairment heterozygous mutant (Disc1het) mice as a model for genetic predisposition. First, Disc1het mice and their littermate control (WT) were fed either a high sucrose diet or a control starch diet for nine weeks starting at weaning (postnatal day 24), and tested for cognitive performance in the object location test (OLT) and the novel object recognition test (NORT) (assessing spatial and recognition memory, respectively). Only Disc1het mice on a high sucrose diet displayed deficits in OLT (p < 0.0001), demonstrating impaired hippocampus-dependent spatial memory. This behavioral abnormality was accompanied by a decreased proportion of the high parvalbumin-expressing interneurons (High-PV neurons) in the ventral hippocampus, a cell type that regulates neural activity and a variety of learning and memory processes such as spatial and working memory. We further explored the critical developmental period for high sucrose intake to cause cognitive deficits in adulthood by comparing specific feeding periods during puberty (P24-P65) and post-puberty (P65-P90). Compared to those on a standard chow diet, high sucrose intake caused deficits in spatial memory in both WT and Disc1het mice, with more pronounced effects in Disc1het mice. In particular, Disc1het mice on a sucrose diet during adolescence showed more pronounced cognitive deficit than those fed after adolescence. Our results suggest that adolescence is particularly vulnerable to nutritional environmental risk factors, and that high sucrose consumption may cause hippocampus-dependent memory deficits via decreased High-PV interneuron function when combined with Disc1-related genetic predisposition.
期刊介绍:
Behavioural Brain Research is an international, interdisciplinary journal dedicated to the publication of articles in the field of behavioural neuroscience, broadly defined. Contributions from the entire range of disciplines that comprise the neurosciences, behavioural sciences or cognitive sciences are appropriate, as long as the goal is to delineate the neural mechanisms underlying behaviour. Thus, studies may range from neurophysiological, neuroanatomical, neurochemical or neuropharmacological analysis of brain-behaviour relations, including the use of molecular genetic or behavioural genetic approaches, to studies that involve the use of brain imaging techniques, to neuroethological studies. Reports of original research, of major methodological advances, or of novel conceptual approaches are all encouraged. The journal will also consider critical reviews on selected topics.