Smidtgarrison4192

The repertoire of binding partners for Elfn1 and Elfn2 includes all group III mGluRs (mGluR4, mGluR6, mGluR7, and mGluR8), and both Elfn1 and Elfn2 can alter mGluR-mediated signaling through trans-interaction. Importantly, both preclinical and clinical studies have provided support for the involvement of the Elfn1-mGluR7 interaction in attention-deficit hyperactivity disorder (ADHD), post-traumatic stress disorder (PTSD), and epilepsy. In fact, Elfn1-mGluR7-associated disorders may reflect the altered function of somatostatin-positive interneuron inhibitory neural circuits, the mesolimbic and nigrostriatal dopaminergic pathway, and habenular circuits, highlighting the need for further investigation into this interaction.We transduced mouse cortical astrocytes cultured from four litters of embryonic wildtype (WT) and connexin43 (Cx43) null mouse pups with lentiviral vector encoding hTERT and measured expression of astrocyte-specific markers up to passage 10 (p10). The immortalized cell lines thus generated (designated IWCA and IKOCA, respectively) expressed biomarkers consistent with those of neonatal astrocytes, including Cx43 from wildtype but not from Cx43-null mice, lack of Cx30, and presence of Cx26. AQP4, the water channel that is found in high abundance in astrocyte end-feet, was expressed at moderately high levels in early passages, and its mRNA and protein declined to low but still detectable levels by p10. The mRNA levels of the astrocyte biomarkers aldehyde dehydrogenase 1L1 (ALDH1L1), glutamine synthetase (GS) and glial fibrillary acidic protein (GFAP) remained relatively constant during successive passages. GS protein expression was maintained while GFAP declined with cell passaging but was still detectable at p1ental manipulation of connexins and live imaging of interactions between connexins and other proteins. We conclude that properties of these cell lines resemble those of primary cultured astrocytes, and they may provide useful tools in functional studies by facilitating genetic and pharmacological manipulations in the context of an astrocyte-appropriate cellular environment.Microglial cells regulate neural homeostasis by coordinating both immune responses and clearance of debris, and the P2X7 receptor for extracellular ATP plays a central role in both functions. The P2X7 receptor is primarily known in microglial cells for its immune signaling and NLRP3 inflammasome activation. However, the receptor also affects the clearance of extracellular and intracellular debris through modifications of lysosomal function, phagocytosis, and autophagy. In the absence of an agonist, the P2X7 receptor acts as a scavenger receptor to phagocytose material. Transient receptor stimulation induces autophagy and increases LC3-II levels, likely through calcium-dependent phosphorylation of AMPK, and activates microglia to an M1 or mixed M1/M2 state. We show an increased expression of Nos2 and Tnfa and a decreased expression of Chil3 (YM1) from primary cultures of brain microglia exposed to high levels of ATP. Sustained stimulation can reduce lysosomal function in microglia by increasing lysosomal pH annce of extracellular debris by microglial cells and mediates lysosomal damage that can activate the NLRP3 inflammasome. A better understanding of how the P2X7 receptor alters phagocytosis, lysosomal health, inflammation, and autophagy can lead to therapies that balance the inflammatory and clearance roles of microglial cells.Rho-associated coiled-coil containing kinase isoform 2 (ROCK2) is a member of the AGC family of serine/threonine kinases and an extensively studied regulator of actin-mediated cytoskeleton contractility. Over the past decade, new evidence has emerged that suggests ROCK2 regulates autophagy. Recent studies indicate that dysregulation of autophagy contributes to the development of misfolded tau aggregates among entorhinal cortex (EC) excitatory neurons in early Alzheimer's disease (AD). While the accumulation of tau oligomers and fibrils is toxic to neurons, autophagy facilitates the degradation of these pathologic species and represents a major cellular pathway for tau disposal in neurons. ROCK2 is expressed in excitatory neurons and pharmacologic inhibition of ROCK2 can induce autophagy pathways. In this mini-review, we explore potential mechanisms by which ROCK2 mediates autophagy and actin dynamics and discuss how these pathways represent therapeutic avenues for Alzheimer's disease.Cerebrospinal fluid-touching neurons (CSF-cNs) exist in the region surrounding the central canal of the spinal cord, which locate in the adult neurogenic niche. Previous research showed that CSF-cNs expressed the molecular markers of immature neural cells in vivo. Here, we explored the potential of CSF-cNs as neural stem cell in intro. We first found that PKD2L1+ CSF-cNs, isolating by FACS using the molecular marker PKD2L1 of CSF-cNs, expressed neural stem cells markers like Nestin, Sox2, and GFAP by immunofluorescence staining. PKD2L1+ CSF-cNs were able to form neurospheres and passaged in vitro. Immunofluorescence staining showed that the neurospheres forming by PKD2L1+ CSF-cNs also expressed neural stem cell markers Nestin, Sox2 and GFAP. The neurospheres expressed proliferation markers Ki67 and PCNA by immunofluorescence staining, indicating that the neurospheres forming by PKD2L1+ CSF-cNs were proliferative. Tanespimycin HSP (HSP90) inhibitor The neurospheres, forming by CSF-cNs, had the ability of differentiation into neurons, astrocytes, and oligodendrocytes. Collectively, our data suggested that PKD2L1+ CSF-cNs have the properties of neural stem cells in vitro and may provide a promising approach for the repair of spinal cord injury.Glioblastoma (GBM) is the most common and aggressive primary brain tumor in the adult population and it carries a dismal prognosis. Inefficient drug delivery across the blood brain barrier (BBB), an immunosuppressive tumor microenvironment (TME) and development of drug resistance are key barriers to successful glioma treatment. Since gliomas occur through sequential acquisition of genetic alterations, gene therapy, which enables to modification of the genetic make-up of target cells, appears to be a promising approach to overcome the obstacles encountered by current therapeutic strategies. Gene therapy is a rapidly evolving field with the ultimate goal of achieving specific delivery of therapeutic molecules using either viral or non-viral delivery vehicles. Gene therapy can also be used to enhance immune responses to tumor antigens, reprogram the TME aiming at blocking glioma-mediated immunosuppression and normalize angiogenesis. Nano-particles-mediated gene therapy is currently being developed to overcome the BBB for glioma treatment.