Neuroscientist最新文献

Empathy is an ability to fully understand and feel the mental states of others. We emphasize that empathy is elicited by the transmission of pain, fear, and sensory information. In clinical studies, impaired empathy has been observed in most psychiatric conditions. However, the precise impairment mechanism of the network systems on the pathogenesis of empathy impairment in psychiatric disorders is still unclear. Multiple lines of evidence suggest that disturbances in the excitatory/inhibitory balance in neurologic disorders are key to empathetic impairment in psychiatric disorders. Therefore, we here describe the roles played by the anterior cingulate cortex- and medial prefrontal cortex-dependent neural circuits and their impairments in psychiatric disorders, including anxiety, depression, and autism. In addition, we review recent studies on the role of microglia in neural network excitation/inhibition imbalance, which contributes to a better understanding of the neural network excitation/inhibition imbalance and may open up innovative psychiatric therapies.

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.

Empathy is usually regarded as the ability to perceive the emotional state of others, which is an altruistic motivation to promote prosocial behavior and thus plays a key role in human life and social development. Empathic pain-the capacity to feel and understand the pain of others-constitutes a significant aspect in the study of empathy behaviors. For an extended duration, investigations into empathic pain have predominantly centered on human neuroimaging studies. Fortunately, recent advancements have witnessed the utilization of animal models in the exploration of the fundamental neural underpinnings of empathic pain. There is substantial evidence implicating multiple brain regions and neural networks in the generation and maintenance of empathic pain. Nevertheless, further elucidation of the neural mechanisms underlying empathic pain is warranted. This review provides a concise overview of prior studies on the neural mechanisms of empathic pain, outlining the pertinent brain regions, neural pathways, synaptic mechanisms, and associated molecules while also delving into future prospects.

Chronic pain is highly prevalent and burdensome, affecting millions of people worldwide. Although it emerges at any point in life, it often manifests in adolescence. Given that adolescence is a unique developmental period, additional strains associated with persistent and often idiopathic pain lead to significant long-term consequences. While there is no singular cause for the chronification of pain, epigenetic modifications that lead to neural reorganization may underpin central sensitization and subsequent manifestation of pain hypersensitivity. Epigenetic processes are particularly active during the prenatal and early postnatal years. We demonstrate how exposure to various traumas, such as intimate partner violence while in utero or adverse childhood experiences, can significantly influence epigenetic regulation within the brain and in turn modify pain-related processes. We provide compelling evidence that the burden of chronic pain is likely initiated early in life, often being transmitted from mother to offspring. We also highlight two promising prophylactic strategies, oxytocin administration and probiotic use, that have the potential to attenuate the epigenetic consequences of early adversity. Overall, we advance understanding of the causal relationship between trauma and adolescent chronic pain by highlighting epigenetic mechanisms that underlie this transmission of risk, ultimately informing how to prevent this rising epidemic.

Traumatic brain injury is a common health problem affecting millions of people each year. BDNF has been investigated in the context of traumatic brain injury due to its crucial role in maintaining brain homeostasis. Val66Met is a functional single-nucleotide polymorphism that results in a valine-to-methionine amino acid substitution at codon 66 in the BDNF prodomain, which ultimately reduces secretion of BDNF. Here, we review experimental animal models as well as clinical studies investigating the role of the Val66Met single-nucleotide polymorphism in traumatic brain injury outcomes, including cognitive function, motor function, neuropsychiatric symptoms, and nociception. We also review studies investigating the role of BDNF on traumatic brain injury pathophysiology as well as circulating BDNF as a biomarker of traumatic brain injury.

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.

The neuronal endoplasmic reticulum (ER) consists of a dynamic, tubular network that extends all the way from the soma into dendrites, axons, and synapses. This morphology gives rise to an enormous membrane surface area that, through the presence of tethering proteins, lipid transfer proteins, and ion channels, plays critical roles in local calcium regulation, membrane dynamics, and the supply of ions and lipids to other organelles. Here, we summarize recent advances that highlight the various roles of the neuronal ER in axonal growth, repair, and presynaptic function. We review the variety of contact sites between the ER and other axonal organelles and describe their influence on neurodevelopment and neurotransmission.

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.

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.