Inhibition of MMP8 effectively alleviates manic-like behavior and reduces neuroinflammation by modulating astrocytic CEBPD.

There is an intrinsic relationship between psychiatric disorders and neuroinflammation, including bipolar disorder. Ouabain, an inhibitor of Na/K-ATPase, has been implicated in the mouse model with manic-like behavior. However, the molecular mechanisms linking neuroinflammation and manic-like behavior require further investigation.

The Design and Fabrication of Large-Area Under-Screen Fingerprint Sensors with Optimized Aperture and Microlens Structures.

In this paper, we designed and fabricated an optical filter structure applied to the FoD (Fingerprint on Display) technology of the smartphone, which contains the microlens array, black matrix, and photodetector to recognize the fingerprint on a full touchscreen. First, we used optical ray tracing software, ZEMAX, to simulate a smartphone with FoD and a touching finger. We then further discussed how the aperture and microlens influence the fingerprint image in this design.

Induction of astrocytic Slc22a3 regulates sensory processing through histone serotonylation.

Neuronal activity drives alterations in gene expression within neurons, yet how it directs transcriptional and epigenomic changes in neighboring astrocytes in functioning circuits is unknown. We found that neuronal activity induces widespread transcriptional up-regulation and down-regulation in astrocytes, highlighted by the identification of as an activity-inducible astrocyte gene that encodes neuromodulator transporter Slc22a3 and regulates sensory processing in the mouse olfactory bulb. Loss of astrocytic Slc22a3 reduced serotonin levels in astrocytes, leading to alterations in histone serotonylation.

Activity-dependent induction of astrocytic Slc22a3 regulates sensory processing through histone serotonylation.

Neuronal activity drives global alterations in gene expression within neurons, yet how it directs transcriptional and epigenomic changes in neighboring astrocytes in functioning circuits is unknown. Here we show that neuronal activity induces widespread transcriptional upregulation and downregulation in astrocytes, highlighted by the identification of a neuromodulator transporter Slc22a3 as an activity-inducible astrocyte gene regulating sensory processing in the olfactory bulb. Loss of astrocytic Slc22a3 reduces serotonin levels in astrocytes, leading to alterations in histone serotonylation.

Olfactory bulb astrocytes mediate sensory circuit processing through Sox9 in the mouse brain.

The role of transcription factors during astrocyte development and their subsequent effects on neuronal development has been well studied. Less is known about astrocytes contributions towards circuits and behavior in the adult brain. Astrocytes play important roles in synaptic development and modulation, however their contributions towards neuronal sensory function and maintenance of neuronal circuit architecture remain unclear.

Glial-Specific Deletion of Med12 Results in Rapid Hearing Loss via Degradation of the Stria Vascularis.

Mediator protein complex subunit 12 (Med12) is a core component of the basal transcriptional apparatus and plays a critical role in the development of many tissues. Mutations in Med12 are associated with X-linked intellectual disability syndromes and hearing loss; however, its role in nervous system function remains undefined. Here, we show that temporal conditional deletion of Med12 in astrocytes in the adult CNS results in region-specific alterations in astrocyte morphology.

Mapping Astrocyte Transcriptional Signatures in Response to Neuroactive Compounds.

Astrocytes play central roles in normal brain function and are critical components of synaptic networks that oversee behavioral outputs. Despite their close affiliation with neurons, how neuronal-derived signals influence astrocyte function at the gene expression level remains poorly characterized, largely due to difficulties associated with dissecting neuron- versus astrocyte-specific effects. Here, we use an in vitro system of stem cell-derived astrocytes to identify gene expression profiles in astrocytes that are influenced by neurons and regulate astrocyte development.

Loss of MeCP2 Function Across Several Neuronal Populations Impairs Breathing Response to Acute Hypoxia.

Rett Syndrome (RTT) is a neurodevelopmental disorder caused by loss of function of the transcriptional regulator Methyl-CpG-Binding Protein 2 (MeCP2). In addition to the characteristic loss of hand function and spoken language after the first year of life, people with RTT also have a variety of physiological and autonomic abnormalities including disrupted breathing rhythms characterized by bouts of hyperventilation and an increased frequency of apnea. These breathing abnormalities, that likely involve alterations in both the circuitry underlying respiratory pace making and those underlying breathing response to environmental stimuli, may underlie the sudden unexpected death seen in a significant fraction of people with RTT.

Regionally Distinct Astrocytes Display Unique Transcription Factor Profiles in the Adult Brain.

Astrocytes are the most abundant type of glial cell in the central nervous system and perform a myriad of vital functions, however, the nature of their diversity remains a longstanding question in neuroscience. Using transcription factor motif discovery analysis on region-specific gene signatures from astrocytes we uncovered universal and region-specific transcription factor expression profiles. This analysis revealed that motifs for Nuclear Factor-I (NFI) are present in genes enriched in astrocytes from all regions, with NFIB and NFIX exhibiting pan-astrocyte expression in the olfactory bulb, hippocampus, cortex, and brainstem.

Nuclear factor I-A regulates diverse reactive astrocyte responses after CNS injury.

Reactive astrocytes are associated with every form of neurological injury. Despite their ubiquity, the molecular mechanisms controlling their production and diverse functions remain poorly defined. Because many features of astrocyte development are recapitulated in reactive astrocytes, we investigated the role of nuclear factor I-A (NFIA), a key transcriptional regulator of astrocyte development whose contributions to reactive astrocytes remain undefined.

Embryonic hindbrain patterning genes delineate distinct cardio-respiratory and metabolic homeostatic populations in the adult.

Previous studies based on mouse genetic mutations suggest that proper partitioning of the hindbrain into transient, genetically-defined segments called rhombomeres is required for normal respiratory development and function in neonates. Less clear is what role these genes and the neurons they define play in adult respiratory circuit organization. Several Cre drivers are used to access and study developmental rhombomeric domains (Eng1 , HoxA2-Cre, Egr2 , HoxB1 , and HoxA4-Cre) in the adult.

Identification of diverse astrocyte populations and their malignant analogs.

Astrocytes are the most abundant cell type in the brain, where they perform a wide array of functions, yet the nature of their cellular heterogeneity and how it oversees these diverse roles remains shrouded in mystery. Using an intersectional fluorescence-activated cell sorting-based strategy, we identified five distinct astrocyte subpopulations present across three brain regions that show extensive molecular diversity. Application of this molecular insight toward function revealed that these populations differentially support synaptogenesis between neurons.

Loss of MeCP2 Causes Urological Dysfunction and Contributes to Death by Kidney Failure in Mouse Models of Rett Syndrome.

Rett Syndrome (RTT) is a neurodevelopmental disorder characterized by loss of acquired skills during development, autonomic dysfunction, and an increased risk for premature lethality. Clinical experience identified a subset of individuals with RTT that present with urological dysfunction including individuals with frequent urinary tract infections, kidney stones, and urine retention requiring frequent catheterization for bladder voiding. To determine if urologic dysfunction is a feature of RTT, we queried the Rett Syndrome Natural History Study, a repository of clinical data from over 1000 individuals with RTT and found multiple instances of urological dysfunction.

Progressive Changes in a Distributed Neural Circuit Underlie Breathing Abnormalities in Mice Lacking MeCP2.

Unlabelled: Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in Methyl-CpG-binding protein 2 (MECP2). Severe breathing abnormalities are common in RTT and are reproduced in mouse models of RTT. Previously, we found that removing MeCP2 from the brainstem and spinal cord in mice caused early lethality and abnormal breathing.

Origin of a Non-Clarke's Column Division of the Dorsal Spinocerebellar Tract and the Role of Caudal Proprioceptive Neurons in Motor Function.

Proprioception, the sense of limb and body position, is essential for generating proper movement. Unconscious proprioceptive information travels through cerebellar-projecting neurons in the spinal cord and medulla. The progenitor domain defined by the basic-helix-loop-helix (bHLH) transcription factor, ATOH1, has been implicated in forming these cerebellar-projecting neurons; however, their precise contribution to proprioceptive tracts and motor behavior is unknown.

Wild-type microglia do not reverse pathology in mouse models of Rett syndrome.

Rett syndrome (RTT) is a severe neurodevelopmental disorder caused by mutations in the X chromosomal gene () (1). RTT treatment so far is symptomatic. disruption in mice phenocopies major features of the syndrome (2) that can be reversed upon re-expression of (.

Mutual antagonism between Sox10 and NFIA regulates diversification of glial lineages and glioma subtypes.

Lineage progression and diversification is regulated by the coordinated action of unique sets of transcription factors. Oligodendrocytes (OL) and astrocytes (AS) comprise the glial sub-lineages in the CNS, and the manner in which their associated regulatory factors orchestrate lineage diversification during development and disease remains an open question. Sox10 and NFIA are key transcriptional regulators of gliogenesis associated with OL and AS.

Atoh1 governs the migration of postmitotic neurons that shape respiratory effectiveness at birth and chemoresponsiveness in adulthood.

Hindbrain neuronal networks serving respiratory, proprioceptive, and arousal functions share a developmental requirement for the bHLH transcription factor Atoh1. Loss of Atoh1 in mice results in respiratory failure and neonatal lethality; however, the neuronal identity and mechanism by which Atoh1-dependent cells sustain newborn breathing remains unknown. We uncovered that selective loss of Atoh1 from the postmitotic retrotrapezoid nucleus (RTN) neurons results in severely impaired inspiratory rhythm and pronounced neonatal death.

Pathogenesis of lethal cardiac arrhythmias in Mecp2 mutant mice: implication for therapy in Rett syndrome.

Rett syndrome is a neurodevelopmental disorder typically caused by mutations in methyl-CpG-binding protein 2 (MECP2) in which 26% of deaths are sudden and of unknown cause. To explore the hypothesis that these deaths may be due to cardiac dysfunction, we characterized the electrocardiograms in 379 people with Rett syndrome and found that 18.5% show prolongation of the corrected QT interval (QTc), an indication of a repolarization abnormality that can predispose to the development of an unstable fatal cardiac rhythm.

MeCP2 is critical within HoxB1-derived tissues of mice for normal lifespan.

Rett syndrome is a neurodevelopmental disorder caused by mutations in methyl-CpG-binding protein 2 (MECP2), a transcriptional regulator. In addition to cognitive, communication, and motor problems, affected individuals have abnormalities in autonomic function and respiratory control that may contribute to premature lethality. Mice lacking Mecp2 die early and recapitulate the autonomic and respiratory phenotypes seen in humans.