Brain Organoid and Systems Neuroscience Journal最新文献

{"title":"Impact of unilateral maximal dentate activation on nitrergic neuron distribution in the hippocampus, entorhinal cortex, gdala and habenula","authors":"Cristiano Bombardi ,&nbsp;Roberto Colangeli ,&nbsp;Maurizio Casarrubea ,&nbsp;Philippe De Deurwaerdère ,&nbsp;Vincenzo Crunelli ,&nbsp;Giuseppe Di Giovanni","doi":"10.1016/j.bosn.2025.100038","DOIUrl":"10.1016/j.bosn.2025.100038","url":null,"abstract":"<div><div>Mesial temporal lobe epilepsy (mTLE) is the most common form of epilepsy involving the hippocampus. While hippocampal circuits have been extensively studied, increasing evidence suggests that extrahippocampal structures, including the amygdala and habenula, may contribute to seizure propagation and epileptogenesis. Among modulators of excitability, nitric oxide (NO) is a key regulator, although its role in mTLE remains controversial, with both pro- and anticonvulsant effects reported.</div><div>We used maximal dentate activation (MDA) in the dentate gyrus, elicited by repeated unilateral perforant path stimulation in rats, a well-established model for studying early mechanisms of epileptogenesis in mTLE. Repeated stimulation progressively shortened MDA onset latency and prolonged seizure duration, reflecting enhanced network excitability. To assess acute nitrergic alterations, an exploratory neuronal NO synthase (nNOS) and NADPH-diaphorase histochemical study wase performed in the hippocampus, entorhinal cortex, amygdala and habenula to determine whether repeated seizures could induce early changes in nitrergic neuronal expression.</div><div>Histochemical analysis revealed region- and layer-specific changes in nitrergic neurons after MDA. In CA1 and CA3, reductions were observed in the stratum oriens, accompanied by an increased density in the CA3 pyramidal layer. The subiculum exhibited a depletion driven by a decrease of nitrergic neurons in the hemisphere contralateral to the stimulation, whereas the entorhinal cortex, basolateral amygdala and medial habenula were largely unaffected. In the lateral habenula, MDA did not alter the overall mean of the density of nitrergic neurons, but it increased it in the stimulated hemisphere and decreased it in the contralateral one.</div><div>This preliminary study reveals adaptations that may indicate a sensitivity of nitrergic neurons to paroxysmal dentate activity and provide a basis for further exploring the potential involvement of NO-related pathways in limbic network responses and TLE-relevant mechanisms and treatments.</div></div>","PeriodicalId":100198,"journal":{"name":"Brain Organoid and Systems Neuroscience Journal","volume":"4 ","pages":"Article 100038"},"PeriodicalIF":0.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145792217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding the contribution of nucleus accumbens D1- and D2-neurons for rewarding and aversive behaviors","authors":"Catarina Carreira ,&nbsp;Ana Verónica Domingues ,&nbsp;Carina Soares-Cunha ,&nbsp;Ana João Rodrigues","doi":"10.1016/j.bosn.2025.11.001","DOIUrl":"10.1016/j.bosn.2025.11.001","url":null,"abstract":"<div><div>The nucleus accumbens (NAc) plays a central role in reward and aversion, strongly modulating motivated behavior. Classical models posited a functional dichotomy in which dopamine receptor D1-medium spiny neurons (MSNs) mediate reward-related behaviors, while D2-MSNs are more relevant for aversive behaviors. However, more recent evidence, including from our project, challenges this framework, demonstrating that both NAc D1- and D2-MSNs can trigger positive and negative reinforcement, depending on circuit context and temporal dynamics. Our project aims to understand the exact contribution of NAc D1- and D2-MSNs in rewarding and aversive behaviors, by enabling cell-type-specific and population-level monitoring of MSN dynamics during behaviorally relevant paradigms including Pavlovian conditioning and reinforcement learning, in combination with neurotransmitter release. This approach is complemented with optogenetic, genetic and pharmacological manipulations of each neuronal population to establish causal links between MSN activity patterns and behavior. This integrated methodology revealed that D1- and D2-MSNs exhibit coordinated (but also distinct) temporal patterns of activity during appetitive and aversive learning. These findings reshape our understanding of NAc function in motivated behavior, and have translational relevance for disorders that present NAc dysfunction and motivational deficits, namely addiction and depression. By bridging advanced circuit dissection with behaviorally meaningful readouts, this project advances the field’s capacity to map, manipulate, and interpret NAc neural activity to understand adaptive and maladaptive motivated behavior.</div></div>","PeriodicalId":100198,"journal":{"name":"Brain Organoid and Systems Neuroscience Journal","volume":"4 ","pages":"Article 100037"},"PeriodicalIF":0.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145927493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disrupted functional connectivity in carotid artery stenosis patients: Insights from fNIRS during a vasoreactivity test","authors":"Víctor Sánchez ,&nbsp;Luis Felipe Bortoletto ,&nbsp;Caroline G. Mazala ,&nbsp;Andrés Quiroga ,&nbsp;Sergio Novi ,&nbsp;Rickson C. Mesquita","doi":"10.1016/j.bosn.2025.03.001","DOIUrl":"10.1016/j.bosn.2025.03.001","url":null,"abstract":"<div><div>Carotid artery stenosis (CAS) reduces cerebral perfusion, which can contribute to neurodegeneration and cognitive decline. While fMRI studies have identified CAS-related disruptions in functional connectivity (FC) associated with neurodegeneration, translating these methods to functional near-infrared spectroscopy (fNIRS) offers a portable, clinically practical alternative. In this study, we assessed FC using fNIRS in 44 CAS patients and 20 controls during breath-holding, a clinical vasoreactivity task. Our results demonstrate clear differences between FC during breath-holding and the resting state, highlighting the task's impact on network connectivity. Patients with unilateral mild stenosis (50–69 % occlusion) exhibited FC patterns comparable to those of controls, whereas patients with bilateral severe stenosis showed a 26 % reduced connectivity and a 14 % lower clustering. When accounting for time delays of 0.9–1.3 seconds, network synchrony was restored across all CAS groups, suggesting that the proposed fNIRS-based method can be used to investigate compensatory hemodynamic delays in CAS. Although sample size limits broader clinical generalizations, this work demonstrates the feasibility of using fNIRS for FC analysis in CAS during a vasodilatory task and provides evidence that fNIRS-based FC metrics are sensitive to CAS severity.</div></div>","PeriodicalId":100198,"journal":{"name":"Brain Organoid and Systems Neuroscience Journal","volume":"3 ","pages":"Pages 36-43"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143679706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trehalose, but not other sugars, protects HT22 cells against amyloid-beta toxicity","authors":"Yue Xu ,&nbsp;Kartar Singh ,&nbsp;Michael A. Beazely ,&nbsp;Zoya Leonenko","doi":"10.1016/j.bosn.2025.04.005","DOIUrl":"10.1016/j.bosn.2025.04.005","url":null,"abstract":"<div><div>Trehalose sugar is being explored as a health supplement in Alzheimer’s Disease due to its neuroprotective potential, which is hypothesized to be mainly due to its regulation of pathological amyloid-beta (Aβ) production and aggregation via metabolic pathways. However, the impact of trehalose on neuronal systems against amyloid toxicity is unclear. This work presents a study of the impact of trehalose at different concentrations on HT22 cell viability and explores whether trehalose can directly reduce cell death caused by exogenous Aβ1–42 oligomers. We used an MTT cell viability assay to evaluate the viability of HT22 cells exposure to exogenous Aβ1–42 oligomers alone or in combination with trehalose and several other sugars. Our results reveal that trehalose has a protective effect on the cell viability against Aβ1–42 oligomers, while other sugars, lactulose, sucrose, and fructose, provided no protection against amyloid toxicity.</div></div>","PeriodicalId":100198,"journal":{"name":"Brain Organoid and Systems Neuroscience Journal","volume":"3 ","pages":"Pages 69-72"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143851521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integration of omics to explore novel disease pathways in Down Syndrome neurodegeneration – Focusing on integrated stress response","authors":"Beatriz Barros-Santos ,&nbsp;Carlos Campos-Marques ,&nbsp;Andreia Filipa Salvador ,&nbsp;Joana Margarida Silva","doi":"10.1016/j.bosn.2025.04.006","DOIUrl":"10.1016/j.bosn.2025.04.006","url":null,"abstract":"<div><div>Down Syndrome is characterized by the trisomy of chromosome 21, leading to widespread molecular and neurological alterations, including early-onset Alzheimer's disease. Emerging evidence highlights the role of RNA metabolism, RNA-binding proteins, and stress granules in these processes. The integrated stress response, a key regulator of translation and protein homeostasis, may be particularly disrupted in DS due to the overexpression of genes involved in the balance between protein degradation and RNA transcription. However, its impact on neurodegeneration in DS remains poorly understood. This project aims to integrate transcriptomic and proteomic data from human and animal models with Down Syndrome to dissect the interplay between integrated stress response, RNA-binding proteins, and stress granule dynamics. By identifying key molecular disruptions in RNA homeostasis and protein synthesis, we aim to investigate novel disease-driving mechanisms that can be conserved among species. These insights will likely help to establish ISR as a potential therapeutic target, advancing our understanding of DS-related neurodegenerative pathways that could be behind the age-related neurodegeneration observed in DS.</div></div>","PeriodicalId":100198,"journal":{"name":"Brain Organoid and Systems Neuroscience Journal","volume":"3 ","pages":"Pages 89-95"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143891785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human cerebral organoids maintain integrity and viability after transport through mail","authors":"Natalie Smith ,&nbsp;Anthony J.A. Baker ,&nbsp;Michaelann S. Tartis ,&nbsp;Zane R. Lybrand","doi":"10.1016/j.bosn.2025.08.001","DOIUrl":"10.1016/j.bosn.2025.08.001","url":null,"abstract":"<div><div>Human cerebral organoids are stem-cell derived three-dimensional (3D) tissue cultures used to advance our understanding of human neurodevelopment processes and neurological disorders. This complex model system can be utilized in interdisciplinary studies that do not include organoid biologists such as engineering, computer science, and pharmacology. This study introduces a reliable method of transportation of live brain organoids to further collaboration amongst disciplines. Using immunohistochemistry and a papain viability assay, we compared the cellular integrity and viability of organoids transported through overnight mail (“flight”) and organoids remaining in the lab (“ground”). In addition, we performed multi-electrode array (MEA) recordings at multiple time points following transport to assess the preservation of spontaneous electrophysiological activity. Our shipping method produced comparable results between flight and ground organoids in viability and cell death staining as well as morphological characteristics of glial cells and neurons. These findings provide a method in transporting organoids between labs to encourage collaboration between brain organoid researchers and non-life scientists.</div></div>","PeriodicalId":100198,"journal":{"name":"Brain Organoid and Systems Neuroscience Journal","volume":"3 ","pages":"Pages 195-201"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144866010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aversive memory engrams in the hippocampus","authors":"Julia Leschik","doi":"10.1016/j.bosn.2025.04.003","DOIUrl":"10.1016/j.bosn.2025.04.003","url":null,"abstract":"<div><div>Negative episodic memories exert important control of behavioral responses during a real or anticipated threatening situation. Under pathological states, however, this control can extend to non-threatening scenarios. For example, pathological states of aversive memory involve fear-overgeneralization in post-traumatic stress disorder (PTSD) or other anxiety disorders. Furthermore, negative bias in cognitive processing and memory formation is seen in depressed individuals displaying enhanced encoding and recall, less forgetting or repetition of negative memory (rumination) as well as impaired recall of positive memory. Beyond pathological conditions, researchers have long aimed to understand the basic biological entity of memory. This unit termed “engram” is the cellular and molecular component of enduring physiological changes in the brain, enabling learning and memory retrieval. Herein, the hippocampus is central in the formation of context-dependent episodic memories and therefore most often studied in animal experiments to elucidate complex memory traces. In addition, the hippocampus is critically involved in fear-circuits and stress-related dysfunction. This review summarizes current knowledge about memory engrams in hippocampal (sub)regions and their functional relevance regarding neuronal correlates and rodent behavior. A special focus is placed on the negative valence of a memory and the formation of engrams for aversive memories, specifically induced by fear or stress. Finally, limitations of current engram research and possible future directions to improve our understanding of negatively valued memory and its implications in neuropathological conditions will be discussed.</div></div>","PeriodicalId":100198,"journal":{"name":"Brain Organoid and Systems Neuroscience Journal","volume":"3 ","pages":"Pages 79-88"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143874437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional connectivity signatures in fMRI-derived connectome for the diagnosis of autism spectrum disorder","authors":"S.M. Shayez Karim,&nbsp;R.S. Rathore","doi":"10.1016/j.bosn.2025.06.004","DOIUrl":"10.1016/j.bosn.2025.06.004","url":null,"abstract":"<div><div>Rearrangement of synaptic connectivity is believed to be involved in shaping neuronal connections during brain developmental in early childhood, which determine mental health and behaviour of an individual. We here compare two types of the functional connectivity patterns: i) changes of healthy infants (3.7–32.6 months) to adults (25–35 yrs), reflecting normal developmental pattern, and ii) changes of healthy infants to autism spectrum disorder (ASD) patients (9.3–35.2 yrs), which encapsulate both developmental and ASD-specific pathological pattern. Using graph-based network parameters in the fMRI-derived connectome, we quantified changes and calculated average and median percent differences of various brain lobes. The connectome-to-connectome comparison suggests that synaptic rewiring is primarily concentrated in intra-thalamic and inter-lobe connections with the thalamus, and the ASD patients were characterised by significant thalamo-cortical hyperconnectivity. The average percent difference of the functional connectivity between ASD patients and adults for thalamus were as high as 82.58 % (degree), 72.8 % (betweenness centrality) 17.41 % (clustering coefficient) and 10.77/15.57 % (global/local efficiency). Regression models were built for normal brain development using functional connection data of healthy infants, child, adolescents and adults for each brain lobe. These regression curves suggest linearly increasing trends of functional connections from infant to adult in all brain lobes except in thalamus. Functional connections of ASD data are significantly different from this trends and characterized by significant overconnectivity. The distinct functional network signatures have the potential to serve as diagnostic markers of ASD. Towards this end, a method has been developed. The method can distinguish ASD subjects from their typically developing peers and healthy individuals with reasonable accuracy and specificity.</div></div>","PeriodicalId":100198,"journal":{"name":"Brain Organoid and Systems Neuroscience Journal","volume":"3 ","pages":"Pages 170-179"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144581138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PIWI-interacting RNAs in neurological and neuropsychiatric disorders and potential for clinical development","authors":"Silvia Beatini ,&nbsp;Letizia La Rosa ,&nbsp;Lidia Giantomasi,&nbsp;Davide De Pietri Tonelli","doi":"10.1016/j.bosn.2025.06.003","DOIUrl":"10.1016/j.bosn.2025.06.003","url":null,"abstract":"<div><div>Neural diseases, including neurological and neuropsychiatric disorders, represent a significant and growing public health burden. While the understanding of the genetic origins of these diseases has advanced considerably in recent years, the underlying causal mechanisms of many sporadic cases remain poorly understood. Recent research highlights the role of noncoding RNAs, such as PIWI-interacting RNAs (piRNAs) and PIWI proteins, in regulating gene expression and maintaining genome stability within neural cells. The piRNA pathway is emerging as a significant regulator of chromatin accessibility and transcriptional homeostasis in nervous system development and plasticity. Concomitantly, a disruption of the piRNA pathway has been associated with neuronal dysfunction and age-associated neuropathologies, underscoring the urgent need to investigate their mechanistic roles in neuronal homeostasis and disease pathogenesis. This review focuses on the emerging functions of the piRNA pathway beyond the gonads, with particular attention given to its potential roles in mammalian nervous system physiology, disease mechanisms, and opportunities for diagnostic and therapeutic development.</div></div>","PeriodicalId":100198,"journal":{"name":"Brain Organoid and Systems Neuroscience Journal","volume":"3 ","pages":"Pages 154-169"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144296389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"On the implementation of single-cell omics and CRISPR screens for iPSC-models of Parkinson’s disease","authors":"Victoria Lievens ,&nbsp;Hugo J.R. Fernandes","doi":"10.1016/j.bosn.2025.04.001","DOIUrl":"10.1016/j.bosn.2025.04.001","url":null,"abstract":"<div><div>Parkinson’s disease (PD) is currently the fastest growing neurological condition, with an urgent need for effective treatments to slow or stop disease progression. The advent of induced pluripotent stem cells (iPSC) models has significantly enhanced our understanding of PD by providing unprecedented access to disease-relevant cell types. These PD <em>in vitro</em> models have provided novels insights into mitochondrial dysfunction, lysosomal and autophagic dysregulation, protein aggregation, stress response, inflammation and metabolic perturbations. However, cellular heterogeneity and variability across iPSC lines are inherent limitations of these models which are often overlooked. Here we discuss ongoing efforts and opportunities to improve PD models by incorporating recent advancements in single-cell multi-omics analyses. We also highlight the lack of genetic CRISPR screens using iPSC-models of PD and discuss current limitations and prospects. We argue that implementing and combining these tools has the potential to unlock novel insights into the pathological mechanisms of PD that could lead to new therapeutic targets for this devastating disorder.</div></div>","PeriodicalId":100198,"journal":{"name":"Brain Organoid and Systems Neuroscience Journal","volume":"3 ","pages":"Pages 73-78"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143868528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}