Developmental Neurobiology最新文献

{"title":"Cellularity Defects Are Not Ubiquitous in the Brains of Fetuses With Down Syndrome","authors":"Marco Emili,&nbsp;Fiorenza Stagni,&nbsp;Maria Paola Bonasoni,&nbsp;Sandra Guidi,&nbsp;Renata Bartesaghi","doi":"10.1002/dneu.22953","DOIUrl":"10.1002/dneu.22953","url":null,"abstract":"<div>\u0000 \u0000 <p>Down syndrome (DS) is a genetic pathology characterized by various developmental defects. Unlike other clinical problems, intellectual disability is an invariant clinical trait of DS. Impairment of neurogenesis accompanied by brain hypotrophy is a typical neurodevelopmental phenotype of DS, suggesting that a reduction in the number of cells forming the brain may be a key determinant of intellectual disability. Previous evidence showed that fetuses with DS exhibit widespread hypocellularity in brain regions belonging to the temporal lobe memory systems, which may account for the typical explicit memory impairment that characterizes DS. In the current study, we have examined the basal ganglia, the insular cortex (INS), and the cingulate cortex (CCX) of fetuses with DS and age-matched controls (18–22 weeks of gestation), to establish whether cellularity defects involve regions that are not primarily involved in explicit memory. We found that fetuses with DS exhibit a notable hypocellularity in the putamen (−30%) and globus pallidus (−35%). In contrast, no cellularity differences were found in the INS and CCX, indicating that hypocellularity is not ubiquitous in the DS brain. The hypocellularity found in the basal ganglia, which are critically implicated in the control of movement, suggests that such alterations may contribute to the motor abnormalities of DS. The normal cytoarchitecture of the INS and CCX suggests that the alterations exhibited by people with DS in functions in which these regions are involved are not attributable to neuron paucity.</p>\u0000 </div>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"84 4","pages":"264-273"},"PeriodicalIF":2.7,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dysregulation of parvalbumin expression and neurotransmitter imbalance in the auditory cortex of the BTBR mouse model of autism spectrum disorder","authors":"Binliang Tang,&nbsp;Jingting Zhao,&nbsp;Cui Zhang,&nbsp;Pengwei Qi,&nbsp;Shuyu Zheng,&nbsp;Chengyuan Xu,&nbsp;Ming Chen,&nbsp;Xiangming Ye","doi":"10.1002/dneu.22952","DOIUrl":"10.1002/dneu.22952","url":null,"abstract":"<p>Individuals diagnosed with autism spectrum disorder (ASD) frequently exhibit abnormalities in auditory perception, a phenomenon potentially attributed to alterations in the excitatory and inhibitory cells constituting cortical circuits. However, the exact genetic factors and cell types affected by ASD remain unclear. The present study investigated the balance of excitatory and inhibitory activity in the auditory cortex using BTBR T⁺ Itpr3^tf/J (BTBR) mice, a well-established model for autism research. Our investigation unveiled a reduction in parvalbumin-positive (PV⁺) neurons within the AC of BTBR mice. Remarkably, in vivo magnetic resonance spectroscopy studies disclosed an elevation in glutamate (Glu) levels alongside a decrement in γ-aminobutyric acid (GABA) levels in this cortical region. Additionally, transcriptomic analysis of the mouse model facilitated the classification of several ASD-associated genes based on their cellular function and pathways. By comparing autism risk genes with RNA transcriptome sequencing data from the ASD mouse model, we identified the recurrent target gene Scn1a and performed validation. Intriguingly, we uncovered the specific expression of Scn1a in cortical inhibitory neurons. These findings hold significant value for understanding the underlying neural mechanisms of abnormal sensory perception in animal models of ASD.</p>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"84 4","pages":"251-263"},"PeriodicalIF":2.7,"publicationDate":"2024-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficient Dlx2-mediated astrocyte-to-neuron conversion and inhibition of neuroinflammation by NeuroD1","authors":"Min-Hui Liu,&nbsp;Yu-Ge Xu,&nbsp;Xiao-Ni Bai,&nbsp;Jian-Hua Lin,&nbsp;Zong-Qin Xiang,&nbsp;Tao Wang,&nbsp;Liang Xu,&nbsp;Gong Chen","doi":"10.1002/dneu.22951","DOIUrl":"10.1002/dneu.22951","url":null,"abstract":"<p>In vivo astrocyte-to-neuron (AtN) conversion induced by overexpression of neural transcriptional factors has great potential for neural regeneration and repair. Here, we demonstrate that a single neural transcriptional factor, Dlx2, converts mouse striatal astrocytes into neurons in a dose-dependent manner. Lineage-tracing studies in Aldh1l1-CreERT2 mice confirm that Dlx2 can convert striatal astrocytes into DARPP32⁺ and Ctip2⁺ medium spiny neurons (MSNs). Time-course studies reveal a gradual conversion from astrocytes to neurons in 1 month, with a distinct intermediate state in between astrocytes and neurons. Interestingly, when Dlx2-infected astrocytes start to lose astrocytic markers, the other local astrocytes proliferate to maintain astrocytic levels in the converted areas. Unexpectedly, although Dlx2 efficiently reprograms astrocytes into neurons in the gray matter striatum, it also induces partial reprogramming of astrocytes in the white matter corpus callosum. Such partial reprogramming of white matter astrocytes is associated with neuroinflammation, which can be suppressed by the addition of NeuroD1. Our results highlight the importance of investigating AtN conversion in both the gray matter and white matter to thoroughly evaluate therapeutic potentials. This study also unveils the critical role of anti-inflammation by NeuroD1 during AtN conversion.</p>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"84 4","pages":"274-290"},"PeriodicalIF":2.7,"publicationDate":"2024-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dneu.22951","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141733789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Application of electrostimulation and magnetic stimulation in patients with optic neuropathy: A mechanistic review","authors":"Mohammad Reza Khalili,&nbsp;Athar Shadmani,&nbsp;Fatemeh Sanie-Jahromi","doi":"10.1002/dneu.22949","DOIUrl":"10.1002/dneu.22949","url":null,"abstract":"<p>Visual impairment caused by optic neuropathies is irreversible because retinal ganglion cells (RGCs), the specialized neurons of the retina, do not have the capacity for self-renewal and self-repair. Blindness caused by optic nerve neuropathies causes extensive physical, financial, and social consequences in human societies. Recent studies on different animal models and humans have established effective strategies to prevent further RGC degeneration and replace the cells that have deteriorated. In this review, we discuss the application of electrical stimulation (ES) and magnetic field stimulation (MFS) in optic neuropathies, their mechanisms of action, their advantages, and limitations. ES and MFS can be applied effectively in the field of neuroregeneration. Although stem cells are becoming a promising approach for regenerating RGCs, the inhibitory environment of the CNS and the long visual pathway from the optic nerve to the superior colliculus are critical barriers to overcome. Scientific evidence has shown that adjuvant treatments, such as the application of ES and MFS help direct thetransplanted RGCs to extend their axons and form new synapses in the central nervous system (CNS). In addition, these techniques improve CNS neuroplasticity and decrease the inhibitory effects of the CNS. Possible mechanisms mediating the effects of electrical current on biological tissues include the release of anti-inflammatory cytokines, improvement of microcirculation, stimulation of cell metabolism, and modification of stem cell function. ES and MFS have the potential to promote angiogenesis, direct axon growth toward the intended target, and enhance appropriate synaptogenesis in optic nerve regeneration.</p>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"84 3","pages":"236-248"},"PeriodicalIF":2.7,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141283207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A C-terminal motif containing a PKC phosphorylation site regulates γ-Protocadherin-mediated dendrite arborization in the cerebral cortex in vivo","authors":"Camille M. Hanes,&nbsp;Kar Men Mah,&nbsp;David M. Steffen,&nbsp;Cathy M. McLeod,&nbsp;Charles G. Marcucci,&nbsp;Leah C. Fuller,&nbsp;Robert W. Burgess,&nbsp;Andrew M. Garrett,&nbsp;Joshua A. Weiner","doi":"10.1002/dneu.22950","DOIUrl":"10.1002/dneu.22950","url":null,"abstract":"<p>The <i>Pcdhg</i> gene cluster encodes 22 γ-Protocadherin (γ-Pcdh) cell adhesion molecules that critically regulate multiple aspects of neural development, including neuronal survival, dendritic and axonal arborization, and synapse formation and maturation. Each γ-Pcdh isoform has unique protein domains—a homophilically interacting extracellular domain and a juxtamembrane cytoplasmic domain—as well as a C-terminal cytoplasmic domain shared by all isoforms. The extent to which isoform-specific versus shared domains regulate distinct γ-Pcdh functions remains incompletely understood. Our previous in vitro studies identified protein kinase C (PKC) phosphorylation of a serine residue within a shared C-terminal motif as a mechanism through which γ-Pcdh promotion of dendrite arborization via myristoylated alanine-rich C-kinase substrate (MARCKS) is abrogated. Here, we used CRISPR/Cas9 genome editing to generate two new mouse lines expressing only non-phosphorylatable γ-Pcdhs, due either to a serine-to-alanine mutation (<i>Pcdhg^S/A</i>) or to a 15-amino acid C-terminal deletion resulting from insertion of an early stop codon (<i>Pcdhg^CTD</i>). Both lines are viable and fertile, and the density and maturation of dendritic spines remain unchanged in both <i>Pcdhg^S/A</i> and <i>Pcdhg^CTD</i> cortex. Dendrite arborization of cortical pyramidal neurons, however, is significantly increased in both lines, as are levels of active MARCKS. Intriguingly, despite having significantly reduced levels of γ-Pcdh proteins, the <i>Pcdhg^CTD</i> mutation yields the strongest phenotype, with even heterozygous mutants exhibiting increased arborization. The present study confirms that phosphorylation of a shared C-terminal motif is a key γ-Pcdh negative regulation point and contributes to a converging understanding of γ-Pcdh family function in which distinct roles are played by both individual isoforms and discrete protein domains.</p>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"84 3","pages":"217-235"},"PeriodicalIF":2.7,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dneu.22950","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141261341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of food additives on neurodevelopmental processes in zebrafish (Danio rerio): Exploring circadian clock genes and dopamine system","authors":"L. Divya Christy,&nbsp;K. Vignesh,&nbsp;Jayshree Nellore,&nbsp;Jayakrishna Tippabathani","doi":"10.1002/dneu.22947","DOIUrl":"10.1002/dneu.22947","url":null,"abstract":"<p>Assessing the impact of food additives on neurodevelopmental processes extends beyond traditional acute toxicity evaluations to address subtler, long-term effects. This study investigates the impact of common food additives (tartrazine, sunset yellow, sodium benzoate, and aspartame) on neurodevelopment in zebrafish embryos, observed from 18 hours postfertilization (hpf) to 91 days postfertilization (dpf). Results show reduced 96 hpf locomotor activity after aspartame exposure, with elevated additives correlating with decreased heart rates and induced neurodegenerative phenotypes, including bent tails and abnormal pigmentation. Although locomotor activity decreases at 7 days postexposure, a gradual recovery is observed. Transcriptome analysis indicates alterations in clock genes (Cry2 and Per2) and dopamine-related genes (NURR1 and tyrosine hydroxylase) in zebrafish larvae. Dietary additive exposure during embryonic development impacts clock genes, influencing dopamine activity and resulting in neurobehavioral changes. This study underscores potential risks associated with dietary additive exposure during critical developmental stages, warranting reconsideration of consumption guidelines, especially for expectant mothers. Observed neurodevelopmental toxicity, even below recommended levels, emphasizes the importance of safeguarding neurodevelopmental health in early life. Our findings contribute to understanding the neurotoxic effects of dietary additives, emphasizing the necessity of protecting neurodevelopment during vulnerable periods. This study is the first to demonstrate a direct correlation between food additives and the dysregulation of key circadian rhythm and dopaminergic genes in zebrafish, providing new insights into the neurodevelopmental impacts of dietary additives. These findings pave the way for further research into the molecular mechanisms and potential implications for human health.</p>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"84 3","pages":"191-202"},"PeriodicalIF":2.7,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141236241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Forebrain commissure formation in zebrafish embryo requires the binding of KLC1 to CRMP2","authors":"Simo Li,&nbsp;Youjia Guo,&nbsp;Miyuki Takahashi,&nbsp;Hisato Suzuki,&nbsp;Kenjiro Kosaki,&nbsp;Toshio Ohshima","doi":"10.1002/dneu.22948","DOIUrl":"10.1002/dneu.22948","url":null,"abstract":"<p>Formation of the corpus callosum (CC), anterior commissure (AC), and postoptic commissure (POC), connecting the left and right cerebral hemispheres, is crucial for cerebral functioning. Collapsin response mediator protein 2 (CRMP2) has been suggested to be associated with the mechanisms governing this formation, based on knockout studies in mice and knockdown/knockout studies in zebrafish. Previously, we reported two cases of non-synonymous CRMP2 variants with S14R and R565C substitutions. Among the, the R565C substitution (p.R565C) was caused by the novel <i>CRMP2</i> mutation c.1693C &gt; T, and the patient presented with intellectual disability accompanied by CC hypoplasia. In this study, we demonstrate that <i>crmp2</i> mRNA could rescue AC and POC formation in <i>crmp2</i>-knockdown zebrafish, whereas the mRNA with the R566C mutation could not. Zebrafish CRMP2 R566C corresponds to human CRMP2 R565C. Further experiments with transfected cultured cells indicated that CRMP2 with the R566C mutation could not bind to kinesin light chain 1 (KLC1). Knockdown of <i>klc1a</i> in zebrafish resulted in defective AC and POC formation, revealing a genetic interaction with <i>crmp2</i>. These findings suggest that the CRMP2 R566C mutant fails to bind to KLC1, preventing axonal elongation and leading to defective AC and POC formation in zebrafish and CC formation defects in humans. Our study highlights the importance of the interaction between CRMP2 and KLC1 in the formation of the forebrain commissures, revealing a novel mechanism associated with CRMP2 mutations underlying human neurodevelopmental abnormalities.</p>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"84 3","pages":"203-216"},"PeriodicalIF":2.7,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141237569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative model of minimal spinal cord injury reveals a rather anti-inflammatory response in the lesion site as well as increased proliferation in the central canal lining in the neonates compared to the adult rats","authors":"Juraj Ševc,&nbsp;Filip Mochnacký,&nbsp;Ján Košuth,&nbsp;Anna Alexovič Matiašová,&nbsp;Lucia Slovinská,&nbsp;Juraj Blaško,&nbsp;Ivan Bukhun,&nbsp;Radovan Holota,&nbsp;Zoltán Tomori,&nbsp;Zuzana Daxnerová","doi":"10.1002/dneu.22942","DOIUrl":"10.1002/dneu.22942","url":null,"abstract":"<p>Spinal cord injury (SCI) resulting from trauma decreases the quality of human life. Numerous clues indicate that the limited endogenous regenerative potential is a result of the interplay between the inhibitory nature of mature nervous tissue and the inflammatory actions of immune and glial cells. Knowledge gained from comparing regeneration in adult and juvenile animals could draw attention to factors that should be removed or added for effective therapy in adults. Therefore, we generated a minimal SCI (mSCI) model with a comparable impact on the spinal cord of Wistar rats during adulthood, preadolescence, and the neonatal period. The mechanism of injury is based on unilateral incision with a 20 ga needle tip according to stereotaxic coordinates into the dorsal horn of the L4 lumbar spinal segment. The incision should harm a similar amount of gray matter on a coronal section in each group of experimental animals. According to our results, the impact causes mild injury with minimal adverse effects on the neurological functions of animals but still has a remarkable effect on nervous tissue and its cellular and humoral components. Testing the mSCI model in adults, preadolescents, and neonates revealed a rather anti-inflammatory response of immune cells and astrocytes at the lesion site, as well as increased proliferation in the central canal lining in neonates compared with adult animals. Our results indicate that developing nervous tissue could possess superior reparative potential and confirm the importance of comparative studies to advance in the field of neuroregeneration.</p>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"84 3","pages":"169-190"},"PeriodicalIF":2.7,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141174902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rare heterozygous genetic variants of NRXN and NLGN gene families involved in synaptic function and their association with neurodevelopmental disorders","authors":"Hamide Betul Gerik-Celebi,&nbsp;Hilmi Bolat,&nbsp;Gul Unsel-Bolat","doi":"10.1002/dneu.22941","DOIUrl":"10.1002/dneu.22941","url":null,"abstract":"<p>The interaction of neurexins (NRXNs) in the presynaptic membrane with postsynaptic cell adhesion molecules called neuroligins (NLGNs) is critical for this synaptic function. Impaired synaptic functions are emphasized in neurodevelopmental disorders to uncover etiological factors. We evaluated variants in <i>NRXN</i> and <i>NLGN</i> genes encoding molecules located directly at the synapse in patients with neuropsychiatric disorders using clinical exome sequencing and chromosomal microarray. We presented detailed clinical findings of cases carrying heterozygous <i>NRXN1</i> (c.190C &gt; T, c.1679C &gt; T and two copy number variations [CNVs]), <i>NRXN2</i> (c.808dup, c.1901G &gt; T), <i>NRXN3</i> (c.3889C &gt; T), and <i>NLGN1</i> (c.269C &gt; G, c.473T &gt; A) gene variants. In addition, three novel variants were identified in the <i>NRXN1</i> (c.1679C &gt; T), <i>NRXN3</i> [c.3889C &gt; T (p.Pro1297Ser)], and <i>NLGN1</i> [c.473T &gt; A (p.Ile158Lys)] genes. We emphasize the clinical findings of CNVs of the <i>NRXN1</i> gene causing a more severe clinical presentation than single nucleotide variants of the <i>NRXN1</i> gene in this study. We detected an <i>NRXN2</i> gene variant (c.808dup) with low allelic frequency in two unrelated cases with the same diagnosis. We emphasize the importance of this variant for future studies. We suggest that <i>NRXN2, NRXN3</i>, and <i>NLGN1</i> genes, which are less frequently reported than <i>NRXN1</i> gene variants, may also be associated with neurodevelopmental disorders.</p>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"84 3","pages":"158-168"},"PeriodicalIF":2.7,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dneu.22941","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140912294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pregestational fructose-induced metabolic syndrome in Wistar rats causes sexually dimorphic behavioral changes in their offspring","authors":"Marié L. Cuervo Sánchez,&nbsp;Facundo H. Prado Spalm,&nbsp;Natalia E. Furland,&nbsp;Ana S. Vallés","doi":"10.1002/dneu.22940","DOIUrl":"10.1002/dneu.22940","url":null,"abstract":"<p>Metabolic syndrome (MetS), marked by enduring metabolic inflammation, has detrimental effects on cognitive performance and brain structure, influencing behavior. This study aimed to investigate whether maternal MetS could negatively impact the neurodevelopment and metabolism of offspring. To test this hypothesis, 2 months old female Wistar rats were subjected to a 10-week regimen of tap water alone or supplemented with 20% fructose to induce MetS. Dams were mated with healthy males to generate litters: OC (offspring from control dams) and OMetS (offspring from dams with MetS). To isolate prenatal effects, all pups were breastfed by control nurse dams, maintaining a standard diet and water ad libitum until weaning. Behavioral assessments were conducted between postnatal days (PN) 22 and 95, and metabolic parameters were analyzed post-sacrifice on PN100. Results from the elevated plus maze, the open field, and the marble burying tests revealed a heightened anxiety-like phenotype in OMetS females. The novel object recognition test showed that exclusively OMetS males had long-term memory impairment. In the reciprocal social interaction test, OMetS displayed a lower number of social interactions, with a notable increase in “socially inactive” behavior observed exclusively in females. Additionally, in the three-chamber test, social preference and social novelty indexes were found to be lower solely among OMetS females. An increase in visceral fat concomitantly with hypertriglyceridemia was the relevant postmortem metabolic finding in OMetS females. In summary, maternal MetS leads to enduring damage and adverse effects on offspring neurobehavior and metabolism, with notable sexual dimorphism.</p>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"84 3","pages":"142-157"},"PeriodicalIF":2.7,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140656178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}