Neuroscientist最新文献_第2页

BDNF: New Views of an Old Player in Traumatic Brain Injury. BDNF：创伤性脑损伤中老角色的新观点。

IF 3.5 3区医学

Neuroscientist Pub Date : 2024-10-01 Epub Date: 2023-04-17 DOI: 10.1177/10738584231164918

Lauren P Giesler, Richelle Mychasiuk, Sandy R Shultz, Stuart J McDonald

引用次数: 0

Autonomic Dysreflexia in Spinal Cord Injury: Mechanisms and Prospective Therapeutic Targets. 脊髓损伤的自主神经反射障碍：机制与前瞻性治疗目标。

IF 3.5 3区医学

Neuroscientist Pub Date : 2024-10-01 Epub Date: 2023-12-12 DOI: 10.1177/10738584231217455

Cameron T Trueblood, Anurag Singh, Marissa A Cusimano, Shaoping Hou

{"title":"Autonomic Dysreflexia in Spinal Cord Injury: Mechanisms and Prospective Therapeutic Targets.","authors":"Cameron T Trueblood, Anurag Singh, Marissa A Cusimano, Shaoping Hou","doi":"10.1177/10738584231217455","DOIUrl":"10.1177/10738584231217455","url":null,"abstract":"High-level spinal cord injury (SCI) often results in cardiovascular dysfunction, especially the development of autonomic dysreflexia. This disorder, characterized as an episode of hypertension accompanied by bradycardia in response to visceral or somatic stimuli, causes substantial discomfort and potentially life-threatening symptoms. The neural mechanisms underlying this dysautonomia include a loss of supraspinal control to spinal sympathetic neurons, maladaptive plasticity of sensory inputs and propriospinal interneurons, and excessive discharge of sympathetic preganglionic neurons. While neural control of cardiovascular function is largely disrupted after SCI, the renin-angiotensin system (RAS), which mediates blood pressure through hormonal mechanisms, is up-regulated after injury. Whether the RAS engages in autonomic dysreflexia, however, is still controversial. Regarding therapeutics, transplantation of embryonic presympathetic neurons, collected from the brainstem or more specific raphe regions, into the injured spinal cord may reestablish supraspinal regulation of sympathetic activity for cardiovascular improvement. This treatment reduces the occurrence of spontaneous autonomic dysreflexia and the severity of artificially triggered dysreflexic responses in rodent SCI models. Though transplanting early-stage neurons improves neural regulation of blood pressure, hormonal regulation remains high and baroreflex dysfunction persists. Therefore, cell transplantation combined with selected RAS inhibition may enhance neuroendocrine homeostasis for cardiovascular recovery after SCI.","PeriodicalId":49753,"journal":{"name":"Neuroscientist","volume":" ","pages":"597-611"},"PeriodicalIF":3.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11166887/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138804958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Endoplasmic Reticulum and Its Contacts: Emerging Roles in Axon Development, Neurotransmission, and Degeneration. 内质网及其联系：轴突发育、神经传递和退化中的新作用

IF 3.5 3区医学

Neuroscientist Pub Date : 2024-10-01 Epub Date: 2023-03-24 DOI: 10.1177/10738584231162810

Marijn Kuijpers, Phuong T Nguyen, Volker Haucke

引用次数: 0

α-Synuclein: Multiple pathogenic roles in trafficking and proteostasis pathways in Parkinson's disease. α-突触核蛋白：在帕金森病的转运和蛋白稳态途径中的多重致病作用

IF 3.5 3区医学

Neuroscientist Pub Date : 2024-10-01 Epub Date: 2024-02-29 DOI: 10.1177/10738584241232963

Annie J Zalon, Drew J Quiriconi, Caleb Pitcairn, Joseph R Mazzulli

{"title":"α-Synuclein: Multiple pathogenic roles in trafficking and proteostasis pathways in Parkinson's disease.","authors":"Annie J Zalon, Drew J Quiriconi, Caleb Pitcairn, Joseph R Mazzulli","doi":"10.1177/10738584241232963","DOIUrl":"10.1177/10738584241232963","url":null,"abstract":"Parkinson's disease (PD) is a common age-related neurodegenerative disorder characterized by the loss of dopaminergic neurons in the midbrain. A hallmark of both familial and sporadic PD is the presence of Lewy body inclusions composed mainly of aggregated α-synuclein (α-syn), a presynaptic protein encoded by the SNCA gene. The mechanisms driving the relationship between α-syn accumulation and neurodegeneration are not completely understood, although recent evidence indicates that multiple branches of the proteostasis pathway are simultaneously perturbed when α-syn aberrantly accumulates within neurons. Studies from patient-derived midbrain cultures that develop α-syn pathology through the endogenous expression of PD-causing mutations show that proteostasis disruption occurs at the level of synthesis/folding in the endoplasmic reticulum (ER), downstream ER-Golgi trafficking, and autophagic-lysosomal clearance. Here, we review the fundamentals of protein transport, highlighting the specific steps where α-syn accumulation may intervene and the downstream effects on proteostasis. Current therapeutic efforts are focused on targeting single pathways or proteins, but the multifaceted pathogenic role of α-syn throughout the proteostasis pathway suggests that manipulating several targets simultaneously will provide more effective disease-modifying therapies for PD and other synucleinopathies.","PeriodicalId":49753,"journal":{"name":"Neuroscientist","volume":" ","pages":"612-635"},"PeriodicalIF":3.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11358363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139991596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Azalea Hypothesis of Alzheimer Disease: A Functional Iron Deficiency Promotes Neurodegeneration. 阿尔茨海默病的杜鹃花假说：功能性缺铁促进神经退行性变

IF 3.5 3区医学

Neuroscientist Pub Date : 2024-10-01 Epub Date: 2023-08-20 DOI: 10.1177/10738584231191743

Steven M LeVine

{"title":"The Azalea Hypothesis of Alzheimer Disease: A Functional Iron Deficiency Promotes Neurodegeneration.","authors":"Steven M LeVine","doi":"10.1177/10738584231191743","DOIUrl":"10.1177/10738584231191743","url":null,"abstract":"Chlorosis in azaleas is characterized by an interveinal yellowing of leaves that is typically caused by a deficiency of iron. This condition is usually due to the inability of cells to properly acquire iron as a consequence of unfavorable conditions, such as an elevated pH, rather than insufficient iron levels. The causes and effects of chlorosis were found to have similarities with those pertaining to a recently presented hypothesis that describes a pathogenic process in Alzheimer disease. This hypothesis states that iron becomes sequestered (e.g., by amyloid β and tau), causing a functional deficiency of iron that disrupts biochemical processes leading to neurodegeneration. Additional mechanisms that contribute to iron becoming unavailable include iron-containing structures not undergoing proper recycling (e.g., disrupted mitophagy and altered ferritinophagy) and failure to successfully translocate iron from one compartment to another (e.g., due to impaired lysosomal acidification). Other contributors to a functional deficiency of iron in patients with Alzheimer disease include altered metabolism of heme or altered production of iron-containing proteins and their partners (e.g., subunits, upstream proteins). A review of the evidence supporting this hypothesis is presented. Also, parallels between the mechanisms underlying a functional iron-deficient state in Alzheimer disease and those occurring for chlorosis in plants are discussed. Finally, a model describing the generation of a functional iron deficiency in Alzheimer disease is put forward.","PeriodicalId":49753,"journal":{"name":"Neuroscientist","volume":" ","pages":"525-544"},"PeriodicalIF":3.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10876915/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10210134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Neuronal Death: Now You See It, Now You Don't. 神经元死亡现在你看到了，现在你看不到了。

IF 3.5 3区医学

Neuroscientist Pub Date : 2024-09-24 DOI: 10.1177/10738584241282632

Trevor Balena, Kevin Staley

引用次数: 0

Neuronal oscillations in cognition: Down syndrome as a model of mouse to human translation. 认知中的神经元振荡：唐氏综合征作为小鼠到人类的转化模型。

IF 3.5 3区医学

Neuroscientist Pub Date : 2024-09-24 DOI: 10.1177/10738584241271414

Pishan Chang, Marta Pérez-González, Jessica Constable, Daniel Bush, Karen Cleverley, Victor L J Tybulewicz, Elizabeth M C Fisher, Matthew C Walker

{"title":"Neuronal oscillations in cognition: Down syndrome as a model of mouse to human translation.","authors":"Pishan Chang, Marta Pérez-González, Jessica Constable, Daniel Bush, Karen Cleverley, Victor L J Tybulewicz, Elizabeth M C Fisher, Matthew C Walker","doi":"10.1177/10738584241271414","DOIUrl":"https://doi.org/10.1177/10738584241271414","url":null,"abstract":"Down syndrome (DS), a prevalent cognitive disorder resulting from trisomy of human chromosome 21 (Hsa21), poses a significant global health concern. Affecting approximately 1 in 800 live births worldwide, DS is the leading genetic cause of intellectual disability and a major predisposing factor for early-onset Alzheimer's dementia. The estimated global population of individuals with DS is 6 million, with increasing prevalence due to advances in DS health care. Global efforts are dedicated to unraveling the mechanisms behind the varied clinical outcomes in DS. Recent studies on DS mouse models reveal disrupted neuronal circuits, providing insights into DS pathologies. Yet, translating these findings to humans faces challenges due to limited systematic electrophysiological analyses directly comparing human and mouse. Additionally, disparities in experimental procedures between the two species pose hurdles to successful translation. This review provides a concise overview of neuronal oscillations in human and rodent cognition. Focusing on recent DS mouse model studies, we highlight disruptions in associated brain function. We discuss various electrophysiological paradigms and suggest avenues for exploring molecular dysfunctions contributing to DS-related cognitive impairments. Deciphering neuronal oscillation intricacies holds promise for targeted therapies to alleviate cognitive disabilities in DS individuals.","PeriodicalId":49753,"journal":{"name":"Neuroscientist","volume":" ","pages":"10738584241271414"},"PeriodicalIF":3.5,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142331106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The effect of traumatic brain injury on learning and memory: A synaptic focus. 创伤性脑损伤对学习和记忆的影响：突触聚焦

IF 3.5 3区医学

Neuroscientist Pub Date : 2024-09-24 DOI: 10.1177/10738584241275583

Eric Eyolfson, Kirsten R B Suesser, Holly Henry, Itziar Bonilla-Del Río, Pedro Grandes, Richelle Mychasiuk, Brian R Christie

{"title":"The effect of traumatic brain injury on learning and memory: A synaptic focus.","authors":"Eric Eyolfson, Kirsten R B Suesser, Holly Henry, Itziar Bonilla-Del Río, Pedro Grandes, Richelle Mychasiuk, Brian R Christie","doi":"10.1177/10738584241275583","DOIUrl":"https://doi.org/10.1177/10738584241275583","url":null,"abstract":"Deficits in learning and memory are some of the most commonly reported symptoms following a traumatic brain injury (TBI). We will examine whether the neural basis of these deficits stems from alterations to bidirectional synaptic plasticity within the hippocampus. Although the CA1 subregion of the hippocampus has been a focus of TBI research, the dentate gyrus should also be given attention as it exhibits a unique ability for adult neurogenesis, a process highly susceptible to TBI-induced damage. This review examines our current understanding of how TBI results in deficits in synaptic plasticity, as well as how TBI-induced changes in endocannabinoid (eCB) systems may drive these changes. Through the synthesis and amalgamation of existing data, we propose a possible mechanism for eCB-mediated recovery in synaptic plasticity deficits. This hypothesis is based on the plausible roles of CB1 receptors in regulating inhibitory tone, influencing astrocytes and microglia, and modulating glutamate release. Dysregulation of the eCBs may be responsible for deficits in synaptic plasticity and learning following TBI. Taken together, the existing evidence indicates eCBs may contribute to TBI manifestation, pathogenesis, and recovery, but it also suggests there may be a therapeutic role for the eCB system in TBI.","PeriodicalId":49753,"journal":{"name":"Neuroscientist","volume":" ","pages":"10738584241275583"},"PeriodicalIF":3.5,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142331107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Navigating Central Oxytocin Transport: Known Realms and Uncharted Territories. 中枢催产素运输导航：已知领域和未知领域。

IF 3.5 3区医学

Neuroscientist Pub Date : 2024-08-07 DOI: 10.1177/10738584241268754

Deniz Parmaksiz, Yongsoo Kim

{"title":"Navigating Central Oxytocin Transport: Known Realms and Uncharted Territories.","authors":"Deniz Parmaksiz, Yongsoo Kim","doi":"10.1177/10738584241268754","DOIUrl":"https://doi.org/10.1177/10738584241268754","url":null,"abstract":"Complex mechanisms govern the transport and action of oxytocin (Oxt), a neuropeptide and hormone that mediates diverse physiologic processes. While Oxt exerts site-specific and rapid effects in the brain via axonal and somatodendritic release, volume transmission via CSF and the neurovascular interface can act as an additional mechanism to distribute Oxt signals across distant brain regions on a slower timescale. This review focuses on modes of Oxt transport and action in the CNS, with particular emphasis on the roles of perivascular spaces, the blood-brain barrier (BBB), and circumventricular organs in coordinating the triadic interaction among circulating blood, CSF, and parenchyma. Perivascular spaces, critical conduits for CSF flow, play a pivotal role in Oxt diffusion and distribution within the CNS and reciprocally undergo Oxt-mediated structural and functional reconstruction. While the BBB modulates the movement of Oxt between systemic and cerebral circulation in a majority of brain regions, circumventricular organs without a functional BBB can allow for diffusion, monitoring, and feedback regulation of bloodborne peripheral signals such as Oxt. Recognition of these additional transport mechanisms provides enhanced insight into the systemic propagation and regulation of Oxt activity.","PeriodicalId":49753,"journal":{"name":"Neuroscientist","volume":" ","pages":"10738584241268754"},"PeriodicalIF":3.5,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141903408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

SARM1-Dependent Axon Degeneration: Nucleotide Signaling, Neurodegenerative Disorders, Toxicity, and Therapeutic Opportunities. SARM1 依赖性轴突退化：核苷酸信号、神经退行性疾病、毒性和治疗机会。

IF 3.5 3区医学

Neuroscientist Pub Date : 2024-08-01 Epub Date: 2023-03-31 DOI: 10.1177/10738584231162508

Helen Y McGuinness, Weixi Gu, Yun Shi, Bostjan Kobe, Thomas Ve

{"title":"SARM1-Dependent Axon Degeneration: Nucleotide Signaling, Neurodegenerative Disorders, Toxicity, and Therapeutic Opportunities.","authors":"Helen Y McGuinness, Weixi Gu, Yun Shi, Bostjan Kobe, Thomas Ve","doi":"10.1177/10738584231162508","DOIUrl":"10.1177/10738584231162508","url":null,"abstract":"Axons are an essential component of the nervous system, and axon degeneration is an early feature of many neurodegenerative disorders. The NAD+ metabolome plays an essential role in regulating axonal integrity. Axonal levels of NAD+ and its precursor NMN are controlled in large part by the NAD+ synthesizing survival factor NMNAT2 and the pro-neurodegenerative NADase SARM1, whose activation triggers axon destruction. SARM1 has emerged as a promising axon-specific target for therapeutic intervention, and its function, regulation, structure, and role in neurodegenerative diseases have been extensively characterized in recent years. In this review, we first introduce the key molecular players involved in the SARM1-dependent axon degeneration program. Next, we summarize recent major advances in our understanding of how SARM1 is kept inactive in healthy neurons and how it becomes activated in injured or diseased neurons, which has involved important insights from structural biology. Finally, we discuss the role of SARM1 in neurodegenerative disorders and environmental neurotoxicity and its potential as a therapeutic target.","PeriodicalId":49753,"journal":{"name":"Neuroscientist","volume":" ","pages":"473-492"},"PeriodicalIF":3.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11282687/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9279120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0