Current research in neurobiology最新文献

{"title":"Apnea of prematurity induces short and long-term development-related transcriptional changes in the murine cerebellum","authors":"A. Rodriguez-Duboc ,&nbsp;M. Basille-Dugay ,&nbsp;A. Debonne ,&nbsp;M.-A. Rivière ,&nbsp;D. Vaudry ,&nbsp;D. Burel","doi":"10.1016/j.crneur.2023.100113","DOIUrl":"https://doi.org/10.1016/j.crneur.2023.100113","url":null,"abstract":"<div><p>Apnea of prematurity (AOP) affects more than 50% of preterm infants and leads to perinatal intermittent hypoxia (IH) which is a major cause of morbimortality worldwide. At birth, the human cerebellar cortex is still immature, making it vulnerable to perinatal events. Additionally, studies have shown a correlation between cerebellar functions and the deficits observed in children who have experienced AOP. Yet, the cerebellar alterations underpinning this link remain poorly understood. To gain insight into the involvement of the cerebellum in perinatal hypoxia-related consequences, we developed a mouse model of AOP. Our previous research has revealed that IH induces oxidative stress in the developing cerebellum, as evidenced by the over-expression of genes involved in reactive oxygen species production and the under-expression of genes encoding antioxidant enzymes. These changes suggest a failure of the defense system against oxidative stress and could be responsible for neuronal death in the cerebellum.</p><p>Building upon these findings, we conducted a transcriptomic study of the genes involved in the processes that occur during cerebellar development. Using real-time PCR, we analyzed the expression of these genes at different developmental stages and in various cell types. This enabled us to pinpoint a timeframe of vulnerability at P8, which represents the age with the highest number of downregulated genes in the cerebellum. Furthermore, we discovered that our IH protocol affects several molecular pathways, including proliferation, migration, and differentiation. This indicates that IH can impact the development of different cell types, potentially contributing to the histological and behavioral deficits observed in this model. Overall, our data strongly suggest that the cerebellum is highly sensitive to IH, and provide valuable insights into the cellular and molecular mechanisms underlying AOP. In the long term, these findings may contribute to the identification of novel therapeutic targets for improving the clinical management of this prevalent pathology.</p></div>","PeriodicalId":72752,"journal":{"name":"Current research in neurobiology","volume":"5 ","pages":"Article 100113"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2665945X23000414/pdfft?md5=3fa9816419f8784a328c4394156b0794&pid=1-s2.0-S2665945X23000414-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91989989","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":"Stuttering as a spectrum disorder: A hypothesis","authors":"Shahriar SheikhBahaei ,&nbsp;Marissa Millwater ,&nbsp;Gerald A. Maguire","doi":"10.1016/j.crneur.2023.100116","DOIUrl":"https://doi.org/10.1016/j.crneur.2023.100116","url":null,"abstract":"<div><p>Childhood-onset fluency disorder, commonly referred to as stuttering, affects over 70 million adults worldwide. While stuttering predominantly initiates during childhood and is more prevalent in males, it presents consistent symptoms during conversational speech. Despite these common clinical manifestations, evidence suggests that stuttering, may arise from different etiologies, emphasizing the need for personalized therapy approaches. Current research models often regard the stuttering population as a singular, homogenous group, potentially overlooking the inherent heterogeneity. This perspective consolidates both historical and recent observations to emphasize that stuttering is a heterogeneous condition with diverse causes. As such, it is crucial that both therapeutic research and clinical practices consider the potential for varied etiologies leading to stuttering. Recognizing stuttering as a spectrum disorder embraces its inherent variability, allowing for a more nuanced categorization of individuals based on the underlying causes. This perspective aligns with the principles of precision medicine, advocating for tailored treatments for distinct subgroups of people who stutter, ultimately leading to personalized therapeutic approaches.</p></div>","PeriodicalId":72752,"journal":{"name":"Current research in neurobiology","volume":"5 ","pages":"Article 100116"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2665945X2300044X/pdfft?md5=e8883614b16b4280c536d3e0f0345e8b&pid=1-s2.0-S2665945X2300044X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91989990","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":"Insulin-like growth factor-1 stimulates retinal cell proliferation via activation of multiple signaling pathways","authors":"Camila Saggioro de Figueiredo ,&nbsp;Ícaro Raony ,&nbsp;Simone Vidal Medina ,&nbsp;Eliezer de Mello Silva ,&nbsp;Aline Araujo dos Santos ,&nbsp;Elizabeth Giestal-de-Araujo","doi":"10.1016/j.crneur.2022.100068","DOIUrl":"10.1016/j.crneur.2022.100068","url":null,"abstract":"<div><p>Insulin-like growth factor-1 (IGF-1) plays critical roles in the development of the central nervous system (CNS), including the retina, regulating cell proliferation, differentiation, and survival. Here, we investigated the role of IGF-1 on retinal cell proliferation using primary cultures from rat neural retina. Our data show that IGF-1 stimulates retinal cell proliferation and regulates the expression of neurotrophic factors, such as interleukin-4 and brain-derived neurotrophic factor. In addition, our results indicates that IGF-1-induced retinal cell proliferation requires activation of multiple signaling pathways, including phosphatidylinositol 3-kinase, protein kinase Src, phospholipase-C, protein kinase C delta, and mitogen-activated protein kinase pathways. We further show that activation of matrix metalloproteinases and epidermal growth factor receptor is also necessary for IGF-1 enhancing retinal cell proliferation. Overall, these results unveil potential mechanisms by which IGF-1 ensures retinal cell proliferation and support the notion that manipulation of IGF-1 signaling may be beneficial in CNS disorders associated with abnormal cell proliferation.</p></div>","PeriodicalId":72752,"journal":{"name":"Current research in neurobiology","volume":"4 ","pages":"Article 100068"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/13/ee/main.PMC9800307.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10458332","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":"The use of chemogenetic actuator ligands in nonhuman primate DREADDs-fMRI","authors":"Adriana K. Cushnie ,&nbsp;Daniel N. Bullock ,&nbsp;Ana M.G. Manea ,&nbsp;Wei Tang ,&nbsp;Jan Zimmermann ,&nbsp;Sarah R. Heilbronner","doi":"10.1016/j.crneur.2022.100072","DOIUrl":"10.1016/j.crneur.2022.100072","url":null,"abstract":"<div><p>Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) are engineered receptors that allow for genetically targeted, reversible manipulation of cellular activity via systemic drug administration. DREADD induced manipulations are initiated via the binding of an actuator ligand. Therefore, the use of DREADDs is contingent on the availability of actuator ligands. Actuator ligands low-dose clozapine (CLZ) and deschloroclozapine (DCZ) are highly selective for DREADDs, and, upon binding, induce physiological and behavioral changes in rodents and nonhuman primates (NHPs). Despite this reported specificity, both CLZ and DCZ have partial affinity for a variety of endogenous receptors and can induce dose-specific changes even in naïve animals. As such, this study aimed to examine the effects of CLZ and DCZ on resting-state functional connectivity (rs-FC) and intrinsic neural timescales (INTs) in naïve NHPs. In doing so, we evaluated whether CLZ and DCZ – in the absence of DREADDs – are inert by examining these ligands’ effects on the intrinsic functional properties of the brain. Low-dose DCZ did not induce consistent changes in rs-FC or INTs prior to the expression of DREADDs; however, a high dose resulted in subject-specific changes in rs-FC and INTs. In contrast, CLZ administration induced consistent changes in rs-FC and INTs prior to DREADD expression in our subjects. Our results caution against the use of CLZ by explicitly demonstrating the impact of off-target effects that can confound experimental results. Altogether, these data endorse the use of low dose DCZ for future DREADD-based experiments.</p></div>","PeriodicalId":72752,"journal":{"name":"Current research in neurobiology","volume":"4 ","pages":"Article 100072"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/07/ee/main.PMC9860110.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9546923","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":"Microscale multicircuit brain stimulation: Achieving real-time brain state control for novel applications","authors":"Yuri B. Saalmann ,&nbsp;Sima Mofakham ,&nbsp;Charles B. Mikell ,&nbsp;Petar M. Djuric","doi":"10.1016/j.crneur.2022.100071","DOIUrl":"10.1016/j.crneur.2022.100071","url":null,"abstract":"<div><p>Neurological and psychiatric disorders typically result from dysfunction across multiple neural circuits. Most of these disorders lack a satisfactory neuromodulation treatment. However, deep brain stimulation (DBS) has been successful in a limited number of disorders; DBS typically targets one or two brain areas with single contacts on relatively large electrodes, allowing for only coarse modulation of circuit function. Because of the dysfunction in distributed neural circuits – each requiring fine, tailored modulation – that characterizes most neuropsychiatric disorders, this approach holds limited promise. To develop the next generation of neuromodulation therapies, we will have to achieve fine-grained, closed-loop control over multiple neural circuits. Recent work has demonstrated spatial and frequency selectivity using microstimulation with many small, closely-spaced contacts, mimicking endogenous neural dynamics. Using custom electrode design and stimulation parameters, it should be possible to achieve bidirectional control over behavioral outcomes, such as increasing or decreasing arousal during central thalamic stimulation. Here, we discuss one possible approach, which we term microscale multicircuit brain stimulation (MMBS). We discuss how machine learning leverages behavioral and neural data to find optimal stimulation parameters across multiple contacts, to drive the brain towards desired states associated with behavioral goals. We expound a mathematical framework for MMBS, where behavioral and neural responses adjust the model in real-time, allowing us to adjust stimulation in real-time. These technologies will be critical to the development of the next generation of neurostimulation therapies, which will allow us to treat problems like disorders of consciousness and cognition.</p></div>","PeriodicalId":72752,"journal":{"name":"Current research in neurobiology","volume":"4 ","pages":"Article 100071"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9816916/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10564607","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":"Layer-specific correlates of detected and undetected auditory targets during attention","authors":"Miriam Heynckes ,&nbsp;Agustin Lage-Castellanos ,&nbsp;Peter De Weerd ,&nbsp;Elia Formisano ,&nbsp;Federico De Martino","doi":"10.1016/j.crneur.2023.100075","DOIUrl":"10.1016/j.crneur.2023.100075","url":null,"abstract":"<div><p>In everyday life, the processing of acoustic information allows us to react to subtle changes in the auditory scene. Yet even when closely attending to sounds in the context of a task, we occasionally miss task-relevant features. The neural computations that underlie our ability to detect behavioral relevant sound changes are thought to be grounded in both feedforward and feedback processes within the auditory hierarchy. Here, we assessed the role of feedforward and feedback contributions in primary and non-primary auditory areas during behavioral detection of target sounds using submillimeter spatial resolution functional magnetic resonance imaging (fMRI) at high-fields (7 T) in humans. We demonstrate that the successful detection of subtle temporal shifts in target sounds leads to a selective increase of activation in superficial layers of primary auditory cortex (PAC). These results indicate that feedback signals reaching as far back as PAC may be relevant to the detection of targets in the auditory scene.</p></div>","PeriodicalId":72752,"journal":{"name":"Current research in neurobiology","volume":"4 ","pages":"Article 100075"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9a/ba/main.PMC9900365.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10742047","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":"Astrocytes: Role in pathogenesis and effect of commonly misused drugs in the HIV infected brain","authors":"Jessalyn Pla-Tenorio ,&nbsp;Angela M. Roig ,&nbsp;Paulina A. García-Cesaní ,&nbsp;Luis A. Santiago ,&nbsp;Marian T. Sepulveda-Orengo ,&nbsp;Richard J. Noel Jr.","doi":"10.1016/j.crneur.2023.100108","DOIUrl":"https://doi.org/10.1016/j.crneur.2023.100108","url":null,"abstract":"<div><p>The roles of astrocytes as reservoirs and producers of a subset of viral proteins in the HIV infected brain have been studied extensively as a key to understanding HIV-associated neurocognitive disorders (HAND). However, their comprehensive role in the context of intersecting substance use and neurocircuitry of the reward pathway and HAND has yet to be fully explained. Use of methamphetamines, cocaine, or opioids in the context of HIV infection have been shown to lead to a faster progression of HAND. Glutamatergic, dopaminergic, and GABAergic systems are implicated in the development of HAND-induced cognitive impairments. A thorough review of scientific literature exploring the variety of mechanisms in which these drugs exert their effects on the HIV brain and astrocytes has revealed marked areas of convergence in overexcitation leading to increased drug-seeking behavior, inflammation, apoptosis, and irreversible neurotoxicity. The present review investigates astrocytes, the neural pathways, and mechanisms of drug disruption that ultimately play a larger holistic role in terms of HIV progression and drug use. There are opportunities for future research, therapeutic intervention, and preventive strategies to diminish HAND in the subset population of patients with HIV and substance use disorder.</p></div>","PeriodicalId":72752,"journal":{"name":"Current research in neurobiology","volume":"5 ","pages":"Article 100108"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49774771","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":"The SARS-CoV-2 spike glycoprotein interacts with MAO-B and impairs mitochondrial energetics","authors":"Chantal A. Pileggi ,&nbsp;Gaganvir Parmar ,&nbsp;Hussein Elkhatib ,&nbsp;Corina M. Stewart ,&nbsp;Irina Alecu ,&nbsp;Marceline Côté ,&nbsp;Steffany A.L. Bennett ,&nbsp;Jagdeep K. Sandhu ,&nbsp;Miroslava Cuperlovic-Culf ,&nbsp;Mary-Ellen Harper","doi":"10.1016/j.crneur.2023.100112","DOIUrl":"https://doi.org/10.1016/j.crneur.2023.100112","url":null,"abstract":"<div><p>SARS-CoV-2 infection is associated with both acute and post-acute neurological symptoms. Emerging evidence suggests that SARS-CoV-2 can alter mitochondrial metabolism, suggesting that changes in brain metabolism may contribute to the development of acute and post-acute neurological complications. Monoamine oxidase B (MAO-B) is a flavoenzyme located on the outer mitochondrial membrane that catalyzes the oxidative deamination of monoamine neurotransmitters. Computational analyses have revealed high similarity between the SARS-CoV-2 spike glycoprotein receptor binding domain on the ACE2 receptor and MAO-B, leading to the hypothesis that SARS-CoV-2 spike glycoprotein may alter neurotransmitter metabolism by interacting with MAO-B. Our results empirically establish that the SARS-CoV-2 spike glycoprotein interacts with MAO-B, leading to increased MAO-B activity in SH-SY5Y neuron-like cells. Common to neurodegenerative disease pathophysiological mechanisms, we also demonstrate that the spike glycoprotein impairs mitochondrial bioenergetics, induces oxidative stress, and perturbs the degradation of depolarized aberrant mitochondria through mitophagy. Our findings also demonstrate that SH-SY5Y neuron-like cells expressing the SARS-CoV-2 spike protein were more susceptible to MPTP-induced necrosis, likely necroptosis. Together, these results reveal novel mechanisms that may contribute to SARS-CoV-2-induced neurodegeneration.</p></div>","PeriodicalId":72752,"journal":{"name":"Current research in neurobiology","volume":"5 ","pages":"Article 100112"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49780847","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":"Dynamic structural remodeling of the human visual system prompted by bilateral retinal gene therapy","authors":"Manzar Ashtari ,&nbsp;Philip Cook ,&nbsp;Mikhail Lipin ,&nbsp;Yinxi Yu ,&nbsp;Gui-Shuang Ying ,&nbsp;Albert Maguire ,&nbsp;Jean Bennett ,&nbsp;James Gee ,&nbsp;Hui Zhang","doi":"10.1016/j.crneur.2023.100089","DOIUrl":"10.1016/j.crneur.2023.100089","url":null,"abstract":"<div><p>The impact of changes in visual input on neuronal circuitry is complex and much of our knowledge on human brain plasticity of the visual systems comes from animal studies. Reinstating vision in a group of patients with low vision through retinal gene therapy creates a unique opportunity to dynamically study the underlying process responsible for brain plasticity. Historically, increases in the axonal myelination of the visual pathway has been the biomarker for brain plasticity. Here, we demonstrate that to reach the long-term effects of myelination increase, the human brain may undergo demyelination as part of a plasticity process. The maximum change in dendritic arborization of the primary visual cortex and the neurite density along the geniculostriate tracks occurred at three months (3MO) post intervention, in line with timing for the peak changes in postnatal synaptogenesis within the visual cortex reported in animal studies. The maximum change at 3MO for both the gray and white matter significantly correlated with patients’ clinical responses to light stimulations called full field sensitivity threshold (FST). Our results shed a new light on the underlying process of brain plasticity by challenging the concept of increase myelination being the hallmark of brain plasticity and instead reinforcing the idea of signal speed optimization as a dynamic process for brain plasticity.</p></div>","PeriodicalId":72752,"journal":{"name":"Current research in neurobiology","volume":"4 ","pages":"Article 100089"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/27/b3/main.PMC10313860.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9745786","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":"Subcortical coding of predictable and unsupervised sound-context associations","authors":"Chi Chen ,&nbsp;Hugo Cruces-Solís ,&nbsp;Alexandra Ertman ,&nbsp;Livia de Hoz","doi":"10.1016/j.crneur.2023.100110","DOIUrl":"https://doi.org/10.1016/j.crneur.2023.100110","url":null,"abstract":"<div><p>Our environment is made of a myriad of stimuli present in combinations often patterned in predictable ways. For example, there is a strong association between where we are and the sounds we hear. Like many environmental patterns, sound-context associations are learned implicitly, in an unsupervised manner, and are highly informative and predictive of normality. Yet, we know little about where and how unsupervised sound-context associations are coded in the brain. Here we measured plasticity in the auditory midbrain of mice living over days in an enriched task-less environment in which entering a context triggered sound with different degrees of predictability. Plasticity in the auditory midbrain, a hub of auditory input and multimodal feedback, developed over days and reflected learning of contextual information in a manner that depended on the predictability of the sound-context association and not on reinforcement. Plasticity manifested as an increase in response gain and tuning shift that correlated with a general increase in neuronal frequency discrimination. Thus, the auditory midbrain is sensitive to unsupervised predictable sound-context associations, revealing a subcortical engagement in the detection of contextual sounds. By increasing frequency resolution, this detection might facilitate the processing of behaviorally relevant foreground information described to occur in cortical auditory structures.</p></div>","PeriodicalId":72752,"journal":{"name":"Current research in neurobiology","volume":"5 ","pages":"Article 100110"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49899182","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}