Yusuflawrence4283

Though the mucus layer is often ignored in the face of dysbiosis, it represents a dynamic and important piece of host machinery that has the potential to impact a wide variety of biological processes. Here, we review evidence supporting the novel concept that stress can modify the delicate mucus-microbiome balance, initiating dysbiosis, and ultimately leading to depression.The proneness to be sexually aroused, to perform sexual acts, or to be sexually disinhibited during a particular mood varies across individuals. However, the physiological mechanisms underlying this specific and variable relationship between mood and sex-related processes are poorly understood. We propose that cortisol may act as an important moderator in this as it has shown to influence sexual arousal and to play a neuromodulatory role during emotion regulation. Here, we conducted a functional magnetic resonance imaging study in a sample of young males to investigate whether cortisol modulates the neural response during the approach of sexual stimuli in an approach-avoidance task and whether this potential relationship explains the individual differences in sexual inhibition and in mood-related sexual interest and activity. We revealed that cortisol associates with the anteromedial prefrontal cortex activation during the approach towards sexual stimuli. Moreover, this anteromedial prefrontal cortex response was dependent on individual differences in sexual inhibition and the improvements of negative mood as a result of sexual activity. The anteromedial prefrontal cortex is already known to process bottom-up information, reward, and risk estimation. The neuromodulatory role of cortisol within this region during sexual approach may represent a previously unknown yet key element in the regulation of sexual behavior in young males.In comparison to conventional repetitive transcranial magnetic stimulation (rTMS), theta burst stimulation is stronger and more effective as a brain stimulation approach within short periods. Although this deep rTMS technique is being applied in treating neuropsychiatric disorders, few animal studies have attempted to clarify the neurobiological mechanisms underlying its beneficial effects. This animal study examined the effects of deep rTMS on the cuprizone-induced neuropathologic and behavioral anomalies and explored the underlying mechanism. Adolescent male C57BL/6 mice were fed a rodent chow without or with cuprizone (CPZ; 0.2% w/w) for 5 weeks. Another two groups of mice were subjected to deep rTMS or sham rTMS once a day during weeks 2-5 of the CPZ-feeding period. The behaviors of all mice were assessed after the withdrawal of CPZ before neuropathological and immunological analyses. Compared to the CNT group, mice in CPZ and CPZ + Sham groups showed deficits in social recognition and spatial working memory as well as anxiety-like behavior, in addition to myelin breakdown and OL loss in the corpus callosum (CC), caudate putamen, cerebral cortex, and hippocampus of the brain. Deep rTMS effectively reduced behavioral anomalies and blocked myelin breakdown and OL loss in CPZ-fed mice. Besides, it also dampened microglia activation at lesion sites and rectified cytokines levels (IL-1β, IL-6, and IL-10) in CPZ-affected regions. The most significant effect was seen in the cerebral cortex where alleviated neuropathology co-existed with less microglia activation and higher IL-10 level. These data provided experimental evidence for the beneficial effects of deep rTMS in CPZ-fed mice and revealed a neurobiological mechanism of the modality.Proopiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus (ARC) plays an essential role in the control of food intake and energy expenditure. Melanocortin-4 receptors (MC4Rs) are expressed in key areas that are implicated in regulating energy homeostasis. Although the importance of MC4Rs in the paraventricular hypothalamus (PVH) has been well documented, the role of MC4Rs in the medial amygdala (MeA) on feeding remains controversial. In this study, we specifically examine the role of a novel ARCPOMC→MeA neural circuit in the regulation of short-term food intake. To map a local melanocortinergic neural circuit, we use monosynaptic anterograde as well as retrograde viral tracers and perform double immunohistochemistry to determine the identity of the neurons receiving synaptic input from POMC neurons in the ARC. To investigate the role of the ARCPOMC→MeA projection on feeding, we optogenetically stimulate channelrhodopsin-2 (ChR2)-expressing POMC fibers in the MeA. Anterograde viral tracing studies reveal that ARC POMC neurons send axonal projections to estrogen receptor-α (ER-α)- and MC4R-expressing neurons in the MeA. Retrograde viral tracing experiments show that the neurons projecting to the MeA is located mainly in the lateral part of the ARC. Optogenetic stimulation of the ARCPOMC→MeA pathway reduces short-term food intake. This anorectic effect is blocked by treatment with the MC4R antagonist SHU9119. In addition to the melanocortinergic local circuits within the hypothalamus, this extrahypothalamic ARCPOMC→MeA neural circuit would play a role in regulating short-term food intake.Neurons typically receive synaptic input in their dendritic arbor, integrate inputs in their soma, and send output action potentials through their axon, following Cajal's law of dynamic polarization. Two notable exceptions are retinal amacrine cells and olfactory granule cells (GCs), which flout Cajal's edict by providing synaptic output from the same dendrites that collect synaptic input. Amacrine cells, a diverse cell class comprising >60 subtypes, employ various dendritic input/output strategies, but A17 amacrine cells (A17s) in particular share further interesting functional characteristics with GCs both receive excitatory synaptic input from neurons in the primary glutamatergic pathway and return immediate, reciprocal feedback via GABAergic inhibitory synapses to the same synaptic terminals that provided input. Both neurons thereby process signals locally within their dendrites, shaping many parallels, signaling pathways independently. The similarities between A17s and GCs cast into relief striking differences that may indicate distinct processing roles within their respective circuits First, they employ partially dissimilar molecular mechanisms to transform excitatory input into inhibitory output; second, GCs fire action potentials, whereas A17s do not. Third, GC signals may be influenced by cortical feedback, whereas the mammalian retina receives no such retrograde input. Finally, A17s constitute just one subtype within a diverse class that is specialized in a particular task, whereas the more homogeneous GCs may play more diverse signaling roles via multiple processing modes. Here, we review these analogies and distinctions between A17 amacrine cells and granule cells, hoping to gain further insight into the operating principles of these two sensory circuits.Vision, hearing, smell, taste, and touch are the tools used to perceive and navigate the world. They enable us to obtain essential resources such as food and highly desired resources such as mates. Thanks to the investments in biomedical research the molecular unpinning's of human sensation are rivaled only by our knowledge of sensation in the laboratory mouse. Humans rely heavily on vision whereas mice use smell as their dominant sense. Both modalities have many features in common, starting with signal detection by highly specialized primary sensory neurons-rod and cone photoreceptors (PR) for vision, and olfactory sensory neurons (OSN) for the smell. In this chapter, we provide an overview of how these two types of primary sensory neurons operate while highlighting the similarities and distinctions.Injuries in the central nervous system (CNS) often causes neuronal loss and glial scar formation. We have recently demonstrated NeuroD1-mediated direct conversion of reactive glial cells into functional neurons in adult mouse brains. Here, we further investigate whether such direct glia-to-neuron conversion technology can reverse glial scar back to neural tissue in a severe stab injury model of the mouse cortex. Using an adeno-associated virus (AAV)-based gene therapy approach, we ectopically expressed a single neural transcription factor NeuroD1 in reactive astrocytes in the injured areas. We discovered that the reactive astrocytes were efficiently converted into neurons both before and after glial scar formation, and the remaining astrocytes proliferated to repopulate themselves. The astrocyte-converted neurons were highly functional, capable of firing action potentials and establishing synaptic connections with other neurons. Unexpectedly, the expression of NeuroD1 in reactive astrocytes resulted in a significant reduction of toxic A1 astrocytes, together with a significant decrease of reactive microglia and neuroinflammation. Furthermore, accompanying the regeneration of new neurons and repopulation of new astrocytes, new blood vessels emerged and blood-brain-barrier (BBB) was restored. These results demonstrate an innovative neuroregenerative gene therapy that can directly reverse glial scar back to neural tissue, opening a new avenue for brain repair after injury.The auditory system relies on temporal precise information transfer, requiring an interplay of synchronously activated inputs and rapid postsynaptic integration. During late postnatal development synaptic, biophysical, and morphological features change to enable mature auditory neurons to perform their appropriate function. How the number of minimal required input fibers and the relevant EPSC time course integrated for action potential generation changes during late postnatal development is unclear. To answer these questions, we used in vitro electrophysiology in auditory brainstem structures from pre-hearing onset and mature Mongolian gerbils of either sex. Synaptic and biophysical parameters changed distinctively during development in the medial nucleus of the trapezoid body (MNTB), the medial superior olive (MSO), and the ventral and dorsal nucleus of the lateral lemniscus (VNLL and DNLL). Despite a reduction in input resistance in most cell types, all required fewer inputs in the mature stage to drive action potentials. Moreover, the EPSC decay time constant is a good predictor of the EPSC time used for action potential generation in all nuclei but the VNLL. Only in MSO neurons, the full EPSC time course is integrated by the neuron's resistive element, while otherwise, the relevant EPSC time matches only 5-10% of the membrane time constant, indicating membrane charging as a dominant role for output generation. We conclude, that distinct developmental programs lead to a general increase in temporal precision and integration accuracy matched to the information relaying properties of the investigated nuclei.Increasing evidence foresees the secretome of neural stem cells (NSCs) to confer superimposable beneficial properties as exogenous NSC transplants in experimental treatments of traumas and diseases of the central nervous system (CNS). Naturally produced secretome biologics include membrane-free signaling molecules and extracellular membrane vesicles (EVs) capable of regulating broad functional responses. The development of high-throughput screening pipelines for the identification and validation of NSC secretome targets is still in early development. Encouraging results from pre-clinical animal models of disease have highlighted secretome-based (acellular) therapeutics as providing significant improvements in biochemical and behavioral measurements. Most of these responses are being hypothesized to be the result of modulating and promoting the restoration of key inflammatory and regenerative programs in the CNS. see more Here, we will review the most recent findings regarding the identification of NSC-secreted factors capable of modulating the immune response to promote the regeneration of the CNS in animal models of CNS trauma and inflammatory disease and discuss the increased interest to refine the pro-regenerative features of the NSC secretome into a clinically available therapy in the emerging field of Regenerative Neuroimmunology.