Front Cell Neurosci
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Front Cell Neurosci · Jan 2018
Clemastine Alleviates Depressive-Like Behavior Through Reversing the Imbalance of Microglia-Related Pro-inflammatory State in Mouse Hippocampus.
Backgrounds: Abundant reports indicate that neuroinflammatory signaling contributes to behavioral complications associated with depression and may be related to treatment response. The glial cells, especially microglia and astrocytes in brain regions of hippocampus and medial prefrontal cortex (mPFC), are major components of CNS innate immunity. Moreover, purinergic receptor P2X, ligand-gated ion channel 7 (P2X7R) was recently reckoned as a pivotal regulator in central immune system. ⋯ Furthermore, clemastine downregulated hippocampal P2X7R without interfering with the expression of HRH1. Conclusion: As a safe and efficient anti-allergic agent, clemastine could impressively alleviate stress-related depressive-like phenotype in mice. Further evidence supported that it was because of the potential function of clemastine in modulating the expression of P2X7 receptor possibly independent of HRH1, therefore suppressing the microglial M1-like activation and pro-inflammatory cytokines release in brain regions of hippocampus rather than mPFC.
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Front Cell Neurosci · Jan 2018
Two-Step Generation of Oligodendrocyte Progenitor Cells From Mouse Fibroblasts for Spinal Cord Injury.
Oligodendrocyte progenitor cells (OPCs) are attracting attention as the ideal cell therapy for spinal cord injury (SCI). Recently, advanced reprogramming and differentiation techniques have made it possible to generate therapeutic cells for treating SCI. In the present study, we used directly-induced neural stem cells (DNSCs) from fibroblasts to establish OPCs (DN-OPCs) capable of proliferation and confirmed their OPC-specific characteristics. ⋯ The DN-OPCs exhibited an OPC-specific phenotype and electrophysiological function and could be differentiated into oligodendrocytes. In the SCI model, transplanted DN-OPCs improved behavior recovery, and showed engraftment into the host spinal cord with expression of myelin basic protein. These results suggest that DN-OPCs could be a new source of potentially useful cells for treating SCI.
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Front Cell Neurosci · Jan 2018
Activation of Astrocytes and Microglial Cells and CCL2/CCR2 Upregulation in the Dorsolateral and Ventrolateral Nuclei of Periaqueductal Gray and Rostral Ventromedial Medulla Following Different Types of Sciatic Nerve Injury.
Peripheral nerve injuries (PNIs) may result in cellular and molecular changes in supraspinal structures possibly involved in neuropathic pain (NPP) maintenance. Activated glial cells in specific supraspinal subregions may affect the facilitatory role of descending pathways. Sterile chronic compression injury (sCCI) and complete sciatic nerve transection (CSNT) in rats were used as NPP models to study the activation of glial cells in the subregions of periaqueductal gray (PAG) and rostral ventromedial medulla (RVM). ⋯ Overall, while CSNT induced robust astrogliosis in both PAG and RVM, microglial cell activation was similar in the supraspinal structures in both injury nerve models. Activated astrocytes in PAG and RVM may sustain facilitation of the descending system maintaining NPP, while microglial activation may be associated with a reaction to long-lasting peripheral injury. Microglial activation via CCR2 may be due to neuronal and astrocytal release of CCL2 in PAG and RVM following injury.
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Front Cell Neurosci · Jan 2018
Fractalkine/CX3CR1 Contributes to Endometriosis-Induced Neuropathic Pain and Mechanical Hypersensitivity in Rats.
Pain is the most severe and common symptom of endometriosis. Its underlying pathogenetic mechanism is poorly understood. Nerve sensitization is a particular research challenge, due to the limitations of general endometriosis models and sampling nerve tissue from patients. ⋯ Intrathecal administration of FKN-neutralizing antibody not only reversed the established mechanical hyperalgesia and allodynia, but also inhibited the expression of CX3CR1/pp38-MAPK in activated microglia, which was essential for the persistence of central sensitization. We concluded that the FKN/CX3CR1 signaling pathway might be one of the mechanisms of peripheral hyperalgesia in endometriosis, which requires further studies. Spinal FKN is important for the development and maintenance of central sensitization in endometriosis, and it may further serve as a novel therapeutic target to relieve persistent pain associated with endometriosis.
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Front Cell Neurosci · Jan 2018
Neuropeptide S Counteracts Paradoxical Sleep Deprivation-Induced Anxiety-Like Behavior and Sleep Disturbances.
Disturbed sleep is a common subjective complaint among individuals with anxiety disorders. Sleep deprivation increases general and specific anxiety symptoms among healthy individuals. The amygdala is critical for regulating anxiety and also involved in mediating the effects of emotions on sleep. ⋯ The majority of Fos-ir neurons induced by NPS also expressed NPSR. These results suggest that NPSR upregulation in the amygdala is presumably related to the PSD-induced anxiety-like behavior and sleep disturbances, and that NPS counteracts PSD-induced anxiety-like behavior and sleep disturbances possibly through activating the neurons bearing NPSR in the amygdala. In addition, the little sleep increase in PSD rats treated with NPS suggests that NPS can function as an anxiolytic without causing a subsequent sleep rebound.