Advances in neurobiology最新文献

Opioid use disorders have become an epidemic in recent years with rates nearly quadrupling since 1999 according to the US Centers for Disease Control and Prevention (Centers for Disease Control, Wide-ranging online data for epidemiologic research (WONDER). CDC, National Center for Health Statistics, Atlanta. Retrieved December 19, 2017, from http://wonder.cdc.gov, 2016). To understand substance use disorder (SUD) as a disease, many aspects must be studied including the circuitry in the brain, adaptations to neuronal circuitry and neurotransmitters, genetic variations increasing the risk for SUD, and treatments available for SUD. The mechanism in which an exogenous opioid may cause SUD is nearly identical to the mechanism of an endogenous opioid. This chapter reviews the clinical and epidemiological aspects of opioid use disorder, as well as the interactions between endogenous and exogenous opioids. Additionally, this chapter discusses current scientific data regarding genetic variations and mechanisms within brain circuitry and the role of endogenous opioids in substance use disorders generally (and opioid use disorder specifically). Future applications of these data to treatment of substance use disorders are also discussed.

This third and final chapter in our trilogy introduces the clinical distinctions and phenotypical similarities between obesity and eating disorders. Research elaborating on the shared neurobiological substrates for obesity and eating disorders is discussed. We present an interprofessional model of treatment for both disordered eating and for obesity. Additionally, this chapter establishes the translational importance of research connecting endogenous opioid activity with both obesity and eating disorders, with an emphasis on clinical interventions. We conclude with a discussion of future directions for research.

Pleasant emotions take a variety of forms and are a key part of the human experience. Although negative emotions have often been a focus of research, positive emotions, e.g., joy, pleasure, and love, have recently gained more attention. Each of these emotions is rich and complex in its own right. However, positive emotions appear to serve key evolutionary functions, which are mediated by complex biological substrates. This chapter summarizes key research and explores the biological underpinnings of positive emotions, with an emphasis on the roles that endogenous opioids play in the experience, expression, and development of positive emotions. The necessity of emphasizing positive emotions in research is also discussed.

The concept of the engram refers to structural and/or physiological changes that underlie memory associations during learning. However, the precise biological basis of the engram remains elusive, with ongoing controversy regarding whether it resides at the cellular level or within the synaptic connections between activated cells. Here, we briefly review the studies investigating the cellular engram and the challenges they encounter. Subsequently, we delve into the biological basis of the engram within synaptic connections. In this regard, we introduce the history of synaptic engrams and discuss recent findings suggesting that synaptic plasticity serves as a substrate for memory. Additionally, we provide an overview of key technologies utilized in the study of synaptic plasticity.

Microglia, immune sentinels of the central nervous system (CNS), play a critical role in maintaining its health and integrity. This chapter delves into the concept of immunometabolism, exploring how microglial metabolism shapes their diverse immune functions. It examines the impact of cell metabolism on microglia during various CNS states, including homeostasis, development, aging, and inflammation. Particularly in CNS inflammation, the chapter discusses how metabolic rewiring in microglia can initiate, resolve, or perpetuate inflammatory responses. The potential of targeting microglial metabolism as a therapeutic strategy for chronic CNS disorders with prominent innate immune cell activation is also explored.

Microglia are highly dynamic cells and acquire different activation states to modulate their multiple functions, which are tightly regulated by the central nervous system microenvironment in which they reside. In response to stress, that is to the appearance of non-physiological signals in their vicinity, microglia will adapt their function in order to promote a return to brain homeostasis. However, when these stress signals are chronically present, microglial response may not be adapted and lead to the establishment of a pathological state. The aim of this book chapter is to examine the substantial literature around the ability of acute and chronic stressors to affect microglial structure and function, with a special focus on psychosocial and nutritional stresses. We also discuss the molecular mechanisms known to date that explain the link between exposure to stressors and microglial activation.

This chapter explores the intricate interactions between neurons and astrocytes within the nervous system with a particular emphasis on studies conducted in human tissue or with human cells. We specifically explore how neuron-astrocyte interactions relate to processes of cellular development, morphology, migration, synapse formation, and metabolism. These findings enrich our understanding of basic neurobiology and how disruptions in these processes are relevant to human diseases.The study of human neuron-astrocyte interactions is made possible because of transformative in vitro advancements that have facilitated the generation and sustained culture of human neural cells. In addition, the rise of techniques like sequencing at single-cell resolution has enabled the exploration of numerous human cell atlases and their comparisons to other animal model systems. Thus, the innovations outlined in this chapter illuminate the convergence and divergence of neuron-astrocyte interactions across species. As technologies progress, continually more sophisticated in vitro systems will increasingly reflect in vivo environments and deepen our command of neuron-glial interactions in human biology.

Autism spectrum disorder (ASD) comprises a complex neurodevelopmental condition characterized by an impairment in social interaction, involving communication deficits and specific patterns of behaviors, like repetitive behaviors. ASD is clinically diagnosed and usually takes time, typically occurring not before four years of age. Genetic mutations affecting synaptic transmission, such as neuroligin and neurexin, are associated with ASD and contribute to behavioral and cognitive deficits. Recent research highlights the role of astrocytes, the brain's most abundant glial cells, in ASD pathology. Aberrant Ca²⁺ signaling in astrocytes is linked to behavioral deficits and neuroinflammation. Notably, the cytokine IL-6 overexpression by astrocytes impacts synaptogenesis. Altered neurotransmitter levels, disruptions in the blood-brain barrier, and cytokine dysregulation further contribute to ASD complexity. Understanding these astrocyte-related mechanisms holds promise for identifying ASD subtypes and developing targeted therapies.

Microglia, brain-resident innate immune cells, have been extensively studied in neurodegenerative contexts like Alzheimer's disease. The Coronavirus disease 2019 (COVID-19) pandemic highlighted how peripheral infection and inflammation can be detrimental to the neuroimmune milieu and initiate microgliosis driven by peripheral inflammation. Microglia can remain deleterious to brain health by sustaining inflammation in the central nervous system even after the clearance of the original immunogenic agents. In this chapter, we discuss how pulmonary infection with Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) can lead to neurovascular and neuroimmune inflammation causing the neurological syndrome of post-acute sequelae of COVID-19 (PASC). Further, we incorporate lessons from the Human Immunodeficiency Virus' (HIV's) effects on microglial functioning in the era of combined antiretroviral therapies (cART) that contribute to HIV-1 associated neurocognitive disorders (HAND). Finally, we describe roles for mixed lineage kinase 3 (MLK3) and leucine-rich repeat kinase (LRRK2) as key regulators of multiple inflammatory and apoptotic pathways important to the pathogenesis of PASC and HAND. Inhibition of these pathways provides a therapeutically synergistic method of treating both PASC and HAND.

The neuroplasticity potential is reduced with aging and impairs during neurodegenerative diseases and brain and visual system injuries. This limits the brain's capacity to repair the structure and dynamics of its activity after lesions. Maximization of neuroplasticity is necessary to provide the maximal CNS response to therapeutic intervention and adaptive reorganization of neuronal networks in patients with degenerative pathology and traumatic injury to restore the functional activity of the brain and retina.Considering the fractal geometry and dynamics of the healthy brain and the loss of fractality in neurodegenerative pathology, we suggest that the application of self-similar visual signals with a fractal temporal structure in the stimulation therapy can reactivate the adaptive neuroplasticity and enhance the effectiveness of neurorehabilitation. This proposition was tested in the recent studies. Patients with glaucoma had a statistically significant positive effect of fractal photic therapy on light sensitivity and the perimetric MD index, which shows that methods of fractal stimulation can be a novel nonpharmacological approach to neuroprotective therapy and neurorehabilitation. In healthy rabbits, it was demonstrated that a long-term course of photostimulation with fractal signals does not harm the electroretinogram (ERG) and retina structure. Rabbits with modeled retinal atrophy showed better dynamics of the ERG restoration during daily stimulation therapy for a week in comparison with the controls. Positive changes in the retinal function can indirectly suggest the activation of its adaptive plasticity and the high potential of stimulation therapy with fractal visual stimuli in a nonpharmacological neurorehabilitation, which requires further study.