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Evidence for Two Subpopulations of Cerebrospinal Fluid-Contacting Neurons with Opposite GABAergic Signaling in Adult Mouse Spinal Cord.
J Neurosci
May 2024
Institut de Neurosciences de la Timone, Aix-Marseille Université (AMU) & CNRS, UMR7289, Marseille 13005, France
Spinal cerebrospinal fluid-contacting neurons (CSF-cNs) form an evolutionary conserved bipolar cell population localized around the central canal of all vertebrates. CSF-cNs were shown to express molecular markers of neuronal immaturity into adulthood; however, the impact of their incomplete maturation on the chloride (Cl) homeostasis as well as GABAergic signaling remains unknown. Using adult mice from both sexes, in situ hybridization revealed that a proportion of spinal CSF-cNs (18.
View Article and Find Full Text PDFConditional deletion of KCC2 impairs synaptic plasticity and both spatial and nonspatial memory.
Front Mol Neurosci
April 2023
Institute of Neuroscience, Université catholique de Louvain, Brussels, Belgium.
The postsynaptic inhibition through GABA receptors (GABAR) relies on two mechanisms, a shunting effect due to an increase in the postsynaptic membrane conductance and, in mature neurons, a hyperpolarization effect due to an entry of chloride into postsynaptic neurons. The second effect requires the action of the K-Cl cotransporter KCC2 which extrudes Cl from the cell and maintains its cytosolic concentration very low. Neuronal chloride equilibrium seems to be dysregulated in several neurological and psychiatric conditions such as epilepsy, anxiety, schizophrenia, Down syndrome, or Alzheimer's disease.
View Article and Find Full Text PDFRole of NKCC1 and KCC2 during hypoxia-induced neuronal swelling in the neonatal neocortex.
Neurobiol Dis
March 2023
Dept. of Pediatrics, The University of Iowa, Iowa City, Iowa, USA; Iowa Neuroscience Institute, The University of Iowa, Iowa City, Iowa, USA; Dept. of Neurology, The University of Iowa, Iowa City, Iowa, USA. Electronic address:
Neonatal hypoxia causes cytotoxic neuronal swelling by the entry of ions and water. Multiple water pathways have been implicated in neurons because these cells lack water channels, and their membrane has a low water permeability. NKCC1 and KCC2 are cation-chloride cotransporters (CCCs) involved in water movement in various cell types.
View Article and Find Full Text PDFThe loop diuretic torasemide but not azosemide potentiates the anti-seizure and disease-modifying effects of midazolam in a rat model of birth asphyxia.
Epilepsy Behav
February 2023
Dept. of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine Hannover, Germany; Center for Systems Neuroscience Hannover, Germany. Electronic address:
Loop diuretics such as furosemide and bumetanide, which act by inhibiting the Na-K-2Cl cotransporter NKCC2 at the thick ascending limb of the loop of Henle, have been shown to exert anti-seizure effects. However, the exact mechanism of this effect is not known. For bumetanide, it has been suggested that inhibition of the NKCC isoform NKCC1 in the membrane of brain neurons may be involved; however, NKCC1 is expressed by virtually all cell types in the brain, which makes any specific targeting of neuronal NKCC1 by bumetanide impossible.
View Article and Find Full Text PDFExpression patterns of NKCC1 in neurons and non-neuronal cells during cortico-hippocampal development.
Cereb Cortex
May 2023
Molecular and Integrative Biosciences, University of Helsinki, 00014 Helsinki, Finland.
The Na-K-2Cl cotransporter NKCC1 is widely expressed in cells within and outside the brain. However, our understanding of its roles in brain functions throughout development, as well as in neuropsychiatric and neurological disorders, has been severely hindered by the lack of reliable data on its developmental and (sub)cellular expression patterns. We provide here the first properly controlled analysis of NKCC1 protein expression in various cell types of the mouse brain using custom-made antibodies and an NKCC1 knock-out validated immunohistochemical procedure, with parallel data based on advanced mRNA approaches.
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