For the small subset of rats in which SE was fully resolved, significant improvements over controls were observed in recovery metrics, behavioral assays, and brain pathology Together these data suggest that NA-induced SE is particularly severe, but aggressive treatment in the intensive care setting can lead to positive functional outcomes for casualtiesMajor facilitator superfamily MFS is the maximum and most diversified membrane transporter, acting as uniporters, symporters and antiporters MFS is considered to have a good development potential in the transport of drugs for the treatment of brain diseases The major facilitator superfamily domain containing protein 2a Mfsd2a is a member of MFS Mfsd2a-knockout mice have shown a marked decrease of docosahexaenoic acid DHA level in brain, exhibiting neuron loss, microcephaly and cognitive deficits, as DHA acts essentially in brain growth and integrity Mfsd2a has attracted more and more attention in the study of nervous system diseases because of its critical role in maintaining the integrity of the blood-brain barrier BBB and transporting DHA, including inhibiting cell transport in central nervous system endothelial cells, alleviating BBB injury, avoiding BBB injury in cerebral hemorrhage model, acting as a carrier etc Up to now, the clinical research of Mfsd2a in nervous system diseases is rare This article reviewed the current research progress of Mfsd2a in nervous system diseases It summarized the physiological functions of Mfsd2a in the occurrence and development of intracranial hemorrhage ICH, Alzheimer's disease AD, sepsis-associated encephalopathy SAE, autosomal recessive primary microcephaly MCPH and intracranial tumor, aiming to provide ideas for the basic research and clinical application of Mfsd2aMajor depressive disorder MDD is a severe mental disorder and is lacking in biomarkers for clinical diagnosis Previous studies have demonstrated that functional abnormalities of the unifying triple networks are the underlying basis of the neuropathology of depression However, whether the functional properties of the triple network are effective biomarkers for the diagnosis of depression remains unclear In our study, we used independent component analysis to define the triple networks, and resting-state functional connectivities RSFCs, effective connectivities EC measured with dynamic causal modeling DCM, and dynamic functional connectivity dFC measured with the sliding window method were applied to map the functional interactions between subcomponents of triple networks Two-sample t-tests with p less then 005 with Bonferroni correction were used to identify the significant differences between healthy controls HCs and MDD Compared with HCs, the MDD showed significantly increased intrinsic FC between the left central executive network CEN and salience network SAL, increased EC from the right CEN to left CEN, decreased EC from the right CEN to the default mode network DMN, and decreased dFC between the right CEN and SAL, DMN Moreover, by fusion of the changed RSFC, EC, and dFC as features, support vector classification could effectively distinguish the MDD from HCs Our results demonstrated that fusion of the multiple functional connectivities measures of the triple networks is an effective way to reveal functional disruptions for MDD, which may facilitate establishing the clinical diagnosis biomarkers for depressionThe human brain contains a wide array of billions of neurons and interconnections, which are often simplified for analysis in vitro using compartmentalized microfluidic devices for neuronal cell culturing, to better understand neuronal development and disease However, such devices are traditionally incompatible for high-pressure freezing and high-resolution nanoscale imaging and analysis of their sub-cellular processes by methods including electron microscopy Here we develop a novel compartmentalized neuronal co-culture platform allowing reconstruction of neuronal networks with high variable spatial control, which is uniquely compatible for high-pressure freezing This cryo-fixation method is well-established to enable high-fidelity preservation of the reconstructed neuronal networks and their sub-cellular processes in a near-native vitreous state without requiring chemical fixatives To direct the outgrowth of neurites originating from two distinct groups of neurons growing in the two different compartmentn using focused ion beam - scanning electron microscopy FIB-SEM and serial sectioning - transmission electron microscopy TEM These results demonstrate the compatibility of the platform with optical microscopy, high-pressure freezing and electron microscopy The platform can be extended to neuronal models of brain disease or development in future studies, enabling the investigation of subcellular processes at the nanoscale within two distinct groups of neurons in a functional neuronal pathway, as well as pharmacological testing and drug screening[11C]Verubulin aka[11C]MCP-6827, [11C]HD-800 and [11C]colchicine have been developed for imaging microtubules MTs with positron emission tomography PET The objective of this work was to conduct an in vivo comparison of [11C]verubulin for MT imaging in mouse and rat brain, as well as an in vitro study with this radiotracer in rodent and human Alzheimer's Disease tissue Our preliminary PET imaging studies of [11C]verubulin in rodents revealed contradictory results between mouse and rat brain uptake under pretreatment conditions In vitro autoradiography with [11C]verubulin showed an unexpected higher uptake in AD patient tissue compared with healthy controls We also conducted the first comparative in vivo PET imaging study with [11C]verubulin, [11C]HD-800 and [11C]colchicine in a non-human primate [11C]Verubulin and [11C]HD-800 require pharmacokinetic modeling and quantification studies to understand the role of how these radiotracers bind to MTs before translation to human useKetamine is a popular recreational substance of abuse that induces persistent behavioral deficits Although disrupted oxytocinergic systems have been considered to modulate vulnerability to developing drugs of abuse, the involvement of central oxytocin in behavioral abnormalities caused by chronic ketamine has remained largely unknown Herein, we aimed to investigate the potential role of oxytocin in the medial prefrontal cortex mPFC in social avoidance and cognitive impairment resulting from repeated ketamine administration in mice We found that ketamine injection 5 mg/kg, ip for 10 days followed by a 6-day withdrawal period induced behavioral disturbances in social interaction and cognitive performance, as well as reduced oxytocin levels both at the periphery and in the mPFC Repeated ketamine exposure also inhibited mPFC neuronal activity as measured by a decrease in c-fos-positive cells Furthermore, direct microinjection of oxytocin into the mPFC reversed the social avoidance and cognitive impairment following chronic ketamine exposure In addition, oxytocin administration normalized ketamine-induced inflammatory cytokines including TNF-α, IL-6, and IL-1β levels Moreover, the activation of immune markers such as neutrophils and monocytes, by ketamine was restored in oxytocin-treated mice Finally, the reversal effects of oxytocin on behavioral performance were blocked by pre-infusion of the oxytocin receptor antagonist atosiban into the mPFC These results demonstrate that enhancing oxytocin signaling in the mPFC is a potential pathway to reverse social avoidance and cognitive impairment caused by ketamine, partly through inhibition of inflammatory stimulationNociceptive nerve endings embedded in muscle tissue transduce peripheral noxious stimuli into an electrical signal [ie, an action potential AP] to initiate pain sensations A major contributor to nociception from the muscles is mechanosensation However, due to the heterogeneity in the expression of proteins, such as ion channels, pumps, and exchangers, on muscle nociceptors, we currently do not know the relative contributions of different proteins and signaling molecules to the neuronal response due to mechanical stimuli In this study, we employed an integrated approach combining a customized experimental study in mice with a computational model to identify key proteins that regulate mechanical nociception in muscles First, using newly collected data from somatosensory recordings in mouse hindpaw muscles, we developed and then validated a computational model of a mechanosensitive mouse muscle nociceptor Next, by performing global sensitivity analyses that simulated thousands of nociceptors, we identified three ion channels among the 17 modeled transmembrane proteins and four endoplasmic reticulum proteins as potential regulators of the nociceptor response to mechanical forces in both the innocuous and noxious range Moreover, we found that simulating single knockouts of any of the three ion channels, delayed rectifier voltage-gated K+ channel Kv11 or mechanosensitive channels Piezo2 or TRPA1, considerably altered the excitability of the nociceptor ie, each knockout increased or decreased the number of triggered APs compared to when all channels were present These results suggest that altering expression of the gene encoding Kv11, Piezo2, or TRPA1 might regulate the response of mechanosensitive muscle nociceptorsKelch-like 1 KLHL1 is a neuronal actin-binding protein that modulates voltage-gated calcium channels The KLHL1 knockout KO model displays altered calcium channel expression in various brain regions We analyzed the electrical behavior of hypothalamic POMC proopiomelanocortin neurons and their response to leptin Leptin's effects on POMC neurons include enhanced gene expression, activation of the ERK1/2 pathway and increased electrical excitability The latter is initiated by activation of the Jak2-PI3K-PLC pathway, which activates TRPC1/5 Transient Receptor Potential Cation channels that in turn recruit T-type channel activity resulting in increased excitability Here we report over-expression of CaV31 T-type channels in the hypothalamus of KLHL1 KO mice increased T-type current density and enhanced POMC neuron basal excitability, rendering them electrically unresponsive to leptin Electrical sensitivity to leptin was restored by partial blockade of T-type channels The overexpression of hypothalamic T-type channels in POMC neurons may partially contribute to the obese and abnormal feeding phenotypes observed in KLHL1 KO miceNeuromodulation is an established treatment for numerous neurological conditions, but to expand the therapeutic scope there is a need to improve the spatial, temporal and cell-type specificity of stimulation Optogenetics is a promising area of current research, enabling optical stimulation of genetically-defined cell types without interfering with concurrent electrical recording for closed-loop control of neural activity We are developing an open-source system to provide a platform for closed-loop optogenetic neuromodulation, incorporating custom integrated circuitry for recording and stimulation, real-time closed-loop algorithms running on a microcontroller and experimental control via a PC interface We include commercial components to validate performance, with the ultimate aim of translating this approach to humans In the meantime our system is flexible and expandable for use in a variety of preclinical neuroscientific applications  https//wwwselleckchemcom/products/Rapamycinhtml  The platform consists of a Controlling Abnormal Network Dynamics using Optogenetics CANDO Control System CS that interfaces with up to four CANDO headstages responsible for electrical recording and optical stimulation through custom CANDO LED optrodes