After peripheral nerve injury, axons are able to regenerate, although specific sensory reinnervation and functional recovery are usually worse for large myelinated than for small sensory axons. The mechanisms that mediate the regeneration of different sensory neuron subpopulations are poorly known. The Na(+)-K(+)-Cl(-) cotransporter 1 (NKCC1) is particularly relevant in setting the intracellular chloride concentration. After axotomy, increased NKCC1 phosphorylation has been reported to be important for neurite outgrowth of sensory neurons; however, the mechanisms underlying its effects are still unknown. In the present study we used in vitro and in vivo models to assess the differential effects of blocking NKCC1 activity on the regeneration of different types of dorsal root ganglia (DRGs) neurons after sciatic nerve injury in the rat. We observed that blocking NKCC1 activity by bumetanide administration induces a selective effect on neurite outgrowth and regeneration of myelinated fibers without affecting unmyelinated DRG neurons. To further study the mechanism underlying NKCC1 effects, we also assessed the changes in mitogen-activated protein kinase (MAPK) signaling under NKCC1 modulation. The inhibition of NKCC1 activity in vitro and in vivo modified pJNK1/2/3 expression in DRG neurons. Together, our study identifies a mechanism selectively contributing to myelinated axon regeneration, and point out the role of Cl(-) modulation in DRG neuron regeneration and in the activation of MAPKs, particularly those belonging to the JNK family.
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http://dx.doi.org/10.1523/JNEUROSCI.4079-14.2015 | DOI Listing |
Adv Sci (Weinh)
December 2024
Department of Neuroscience, University of Copenhagen, Blegdamsvej 3, Copenhagen N, 2200, Denmark.
Disturbances in the brain fluid balance can lead to life-threatening elevation in intracranial pressure (ICP), which represents a vast clinical challenge. Targeted and efficient pharmaceutical therapy of elevated ICP is not currently available, as the molecular mechanisms governing cerebrospinal fluid (CSF) secretion are largely unresolved. To resolve the quantitative contribution of key choroid plexus transport proteins, this study employs mice with genetic knockout and/or viral choroid plexus-specific knockdown of aquaporin 1 (AQP1) and the Na, K, 2Cl cotransporter 1 (NKCC1) for in vivo determinations of CSF dynamics, ex vivo choroid plexus for transporter-mediated clearance of a CSF K load, and patient CSF for [K] quantification.
View Article and Find Full Text PDFBrain Behav Immun Health
December 2024
Departments of Neurology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
Interleukin 18 (IL-18), a proinflammatory cytokine, has been implicated in various neurological disorders, including cerebrovascular disease and psychiatric disorders. In a previous study, IL-18 was observed to activate microglia and enhance the inflammatory response following intracranial hemorrhage (ICH). However, the underlying mechanism remains unclear.
View Article and Find Full Text PDFFront Immunol
November 2024
Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology and Beijing Laboratory of Oral Health, Beijing, China.
Introduction: Primary Sjögren syndrome (pSS) is a systemic autoimmune disease that is characterized by the infiltration of immune cells into the salivary glands. The re-establishment of salivary glands (SGs) function in pSS remains a clinical challenge. Myeloid-derived growth factor (MYDGF) has anti-inflammatory, immunomodulatory, and tissue-functional restorative abilities.
View Article and Find Full Text PDFCNS Neurosci Ther
October 2024
Department of Neurology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.
Background: Hydrocephalus is characterized by secretion, circulation, and absorption disorder of cerebrospinal fluid (CSF) with high morbidity and complication rate. The relationship between inflammation and abnormal secretion of CSF by choroid plexus epithelium (CPE) had received more attention. In this study, we aim to detect the role of Toll-like receptor 4/nuclear factor-kappa B/Na+/K+/2Cl-cotransporter 1(TLR4/NF-κB/NKCC1) signal pathway in the development of hydrocephalus.
View Article and Find Full Text PDFInt J Mol Sci
September 2024
Departamento de Fisiología, Facultad de Biología, Universidad de Sevilla, 41012 Sevilla, Spain.
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