Neuroscientist最新文献

As a monovalent cation channel, the transient receptor potential melastatin 4 (TRPM4) channel is a unique member of the transient receptor potential family. Abnormal TRPM4 activity has been identified in various neurologic disorders, such as stroke, spinal cord injury, traumatic brain injury, multiple sclerosis, amyotrophic lateral sclerosis, pathologic pain, and epilepsy. Following brain hypoxia/ischemia and inflammation, TRPM4 up-regulation and enhanced activity contribute to the cell death of neurons, vascular endothelial cells, and astrocytes. Enhanced ionic influx via TRPM4 leads to cell volume increase and oncosis. Depolarization of membrane potential following TRPM4 activation and interaction between TRPM4 and N-methyl-d-aspartate receptors exacerbate excitotoxicity during hypoxia. Importantly, TRPM4 expression and activity remain low in healthy neurons, making it an ideal drug target. Current approaches to inhibit or modulate the TRPM4 channel have various limitations that hamper the interpretation of TRPM4 physiology in the nervous system and potentially hinder their translation into therapy. In this review, we discuss the pathophysiologic roles of TRPM4 and the different inhibitors that modulate TRPM4 activity for potential treatment of neurologic diseases.

Human society is organized in structured social networks upon which large-scale cooperation among genetically unrelated individuals is favored and persists. Such large-scale cooperation is crucial for the success of the human species but also one of the most puzzling challenges. Recent work in social and behavioral neuroscience has linked human cooperation to oxytocin, an evolutionarily ancient and structurally preserved hypothalamic neuropeptide. This review aims to elucidate how oxytocin promotes nonkin cooperation in social networks by reviewing its effects at three distinct levels: individual cooperation, the formation of interpersonal relationships, and the establishment of heterogeneous network structures. We propose oxytocin as a proximate mechanism for fostering large-scale cooperation in human societies. Specifically, oxytocin plays an important role in facilitating network-wide cooperation in human societies by 1) increasing individual cooperation, mitigating noncooperation motives, and facilitating the enforcement of cooperative norms; 2) fostering interpersonal bonding and synchronization; and 3) facilitating the formation of heterogeneous network structures.

The mammalian brain comprises two structurally and functionally distinct compartments: the gray matter (GM) and the white matter (WM). In humans, the WM constitutes approximately half of the brain volume, yet it remains significantly less investigated than the GM. The major cellular elements of the WM are neuronal axons and glial cells. However, the WM also contains cell bodies of the interstitial neurons, estimated to number 10 to 28 million in the adult bat brain, 67 million in Lar gibbon brain, and 450 to 670 million in the adult human brain, representing as much as 1.3%, 2.25%, and 3.5% of all neurons in the cerebral cortex, respectively. Many studies investigated the interstitial WM neurons (IWMNs) using immunohistochemistry, and some information is available regarding their electrophysiological properties. However, the functional role of IWMNs in physiologic and pathologic conditions largely remains unknown. This review aims to provide a concise update regarding the distribution and properties of interstitial WM neurons, highlight possible functions of these cells as debated in the literature, and speculate about other possible functions of the IWMNs and their interactions with glial cells. We hope that our review will inspire new research on IWMNs, which represent an intriguing cell population in the brain.

Swelling, stiffness, and pain in synovial joints are primary hallmarks of osteoarthritis and rheumatoid arthritis. Hyperactivity of nociceptors and excessive release of inflammatory factors and pain mediators play a crucial role, with emerging data suggesting extensive remodelling and plasticity of joint innervations. Herein, we review structural, functional, and molecular alterations in sensory and autonomic axons wiring arthritic joints and revisit mechanisms implicated in the sensitization of nociceptors, leading to chronic pain. Sprouting and reorganization of sensory and autonomic fibers with the invasion of ectopic branches into surrounding inflamed tissues are associated with the upregulation of pain markers. These changes are frequently complemented by a phenotypic switch of sensory and autonomic profiles and activation of silent axons, inferring homeostatic adjustments and reprogramming of innervations. Identifying critical molecular players and neurobiological mechanisms underpinning the rewiring and sensitization of joints is likely to elucidate causatives of neuroinflammation and chronic pain, assisting in finding new therapeutic targets and opportunities for interventions.

Autophagies describe a set of processes in which cells degrade their cytoplasmic contents via various routes that terminate with the lysosome. In macroautophagy (the focus of this review, henceforth autophagy), cytoplasmic contents, including misfolded proteins, protein complexes, dysfunctional organelles, and various pathogens, are captured within double membranes called autophagosomes, which ultimately fuse with lysosomes, after which their contents are degraded. Autophagy is important in maintaining neuronal and glial function; consequently, disrupted autophagy is associated with various neurologic diseases. This review provides a broad perspective on the roles of autophagy in the CNS, highlighting recent literature that furthers our understanding of the multifaceted role of autophagy in maintaining a healthy nervous system.

The current study investigates the intricate connection between neurology and islands shedding light on the historical, epidemiological, and genetic aspects. Based on an elaborate literature review, we identified neurological conditions having a significant clustering in an island(s), confined to a particular island(s), named after an island, and described first in an island. The genetic factors played a crucial role, uncovering disorders like Cayman ataxia, Machado Joseph disease, SGCE-mediated dystonia-myoclonus syndrome, X-linked dystonia parkinsonism, hereditary transthyretinrelated amyloidosis, Charcot Marie Tooth 4F, and progressive myoclonic epilepsy syndromes, that exhibited remarkable clustering in diverse islands. Local customs also left enduring imprints. Practices such as cannibalism in Papua New Guinea led to Kuru, while cycad seed consumption in Guam triggered Lytico-Bodig disease. Toxin-mediated neurologic disorders exhibited intricate island connections, exemplified by Minamata disease in Kyushu islands and atypical parkinsonism in French Caribbean islands. Additionally, the Cuban epidemic of amblyopia and neuropathy was associated with severe nutritional deficiencies. This study pioneers a comprehensive review narrating the genetic, environmental, and cultural factors highlighting the spectrum of neurological disorders in island settings. It enriches the medical literature with a unique understanding of the diverse influences shaping neurological health in island environments.

Fatally injured neurons may necrose and rupture immediately, or they may initiate a programmed cell death pathway and then wait for microglial phagocytosis. Biochemical and histopathologic assays of neuronal death assess the numbers of neurons awaiting phagocytosis at a particular time point after injury. This number varies with the fraction of neurons that have necrosed vs initiated programmed cell death, the time elapsed since injury, the rate of phagocytosis, and the assay's ability to detect neurons at different stages of programmed cell death. Many of these variables can be altered by putatively neurotoxic and neuroprotective interventions independent of the effects on neuronal death. This complicates analyses of neurotoxicity and neuroprotection and has likely contributed to difficulties with clinical translation of neuroprotective strategies after brain injury. Time-resolved assays of neuronal health, such as ongoing expression of transgenic fluorescent proteins, are a useful means of avoiding these problems.