The canonical physiological role of leptin is to regulate hunger and satiety acting on specific hypothalamic nuclei. Beyond this key metabolic function; leptin also regulates many aspects of development and functioning of neuronal hippocampal networks throughout life. Here we show that leptin controls chloride homeostasis in the developing rat hippocampus in vitro. The effect of leptin relies on the down-regulation of the potassium/chloride extruder KCC2 activity and is present during a restricted period of postnatal development. This study confirms and extends the role of leptin in the ontogenesis of functional GABAergic inhibition and helps understanding how abnormal levels of leptin may contribute to neurological disorders.
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http://dx.doi.org/10.1186/s13041-020-00689-z | DOI Listing |
Front Mol Neurosci
December 2024
Axonis Therapeutics Inc., Boston, MA, United States.
KCC2 is CNS neuron-specific chloride extruder, essential for the establishment and maintenance of the transmembrane chloride gradient, thereby enabling synaptic inhibition within the CNS. Herein, we highlight KCC2 hypofunction as a fundamental and conserved pathology contributing to neuronal circuit excitation/inhibition (E/I) imbalances that underly epilepsies, chronic pain, neuro-developmental/-traumatic/-degenerative/-psychiatric disorders. Indeed, downstream of both acquired and genetic factors, multiple pathologies (e.
View Article and Find Full Text PDFBrain Res Bull
December 2024
Department of Rehabilitation, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; Chongqing Key Laboratory of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. Electronic address:
Background: Transcranial direct current stimulation (tDCS) has an impact on improving cognitive and motor dysfunction induced by ischemia-reperfusion injury. However, to use this technology more rationally in clinical practice, a deepened understanding of the molecular mechanisms behind its therapeutic effects is needed. This study explored the role of the brain-derived neurotrophic factor(BDNF) and its associated receptor tropomyosin-receptor kinase B(TrkB) while deciphering the underlying mechanisms in transcranial direct current therapy to treat ischemic stroke.
View Article and Find Full Text PDFInt J Biol Macromol
December 2024
Department of Pain, Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China. Electronic address:
Impaired spinal GABAergic inhibitory neuronal system is one popular target for developing new drugs or procedures for treatment of neuropathic pain, but effective and transferable methods are still lacking. We designed an assembled, temperature sensitive and sustained releasing hydrogel to repair the impaired GABAergic neural system by reversing imbalance of glutamic acid (Glu) and γ-aminobutyric acid (GABA) and healing impaired Cl extrusion capacity of neurons. Hydrogel solution is a mixture of pluronic F-127, recombinant glutamate decarboxylase 67 (rGAD67) protein and CLP257, a K-Cl cotransporter isoform 2 (KCC2) enhancer.
View Article and Find Full Text PDFThe ability to associate environmental stimuli with positive outcomes is a fundamental form of learning. While extensive research has focused on the response profiles of midbrain dopamine neurons during associative learning, less is known about learning-mediated changes in the afferents that shape their responses. We demonstrate that during critical phases of learning, anion homeostasis in midbrain GABA neurons - a primary source of input to dopamine neurons - is disrupted due to downregulation of the chloride transporter KCC2.
View Article and Find Full Text PDFInt J Mol Sci
November 2024
Myology Lab, Institute of Biomedical Problems of the Russian Academy of Sciences, 123007 Moscow, Russia.
In most mammals, postural soleus muscles are involved in the maintenance of the stability of the body in the gravitational field of Earth. It is well established that immediately after a laboratory rat is exposed to conditions of weightlessness (parabolic flight) or simulated microgravity (hindlimb suspension/unloading), a sharp decrease in soleus muscle electrical activity occurs. However, starting from the 3rd day of mechanical unloading, soleus muscle electrical activity begins to increase and reaches baseline levels approximately by the 14th day of hindlimb suspension.
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