Neuroscience letters
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Neuroscience letters · Sep 2020
Neonatal exposure to sevoflurane expands the window of vulnerability to adverse effects of subsequent exposure to sevoflurane and alters hippocampal morphology via decitabine-sensitive mechanisms.
Deficiencies in neurocognitive function have been found in late childhood or adolescence in patients who had prolonged and/or repeated early-life general anesthesia. Animal studies suggest that anesthetic-induced impairment in the neuron-specific K+-2Cl- (Kcc2) Cl- exporter expression, which regulates developmental maturation of GABA type A receptor (GABAAR) signaling from excitatory to inhibitory, may play a mediating role. We tested whether the DNA methyltransferase (DNMT) inhibitor decitabine ameliorates the anesthetic's adverse effects. ⋯ Neonatal exposure to sevoflurane sensitizes rats to adverse effects of repeated exposure to the anesthetic. The anesthetic-caused changes in the decitabine-sensitive mechanisms may play a mediating role in the developmental effects of early-life anesthesia.
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Neuroscience letters · Sep 2020
Netrin-1 contributes to peripheral nerve injury induced neuropathic pain via regulating phosphatidylinositol 4-kinase IIa in the spinal cord dorsal horn in mice.
The burden of neuropathic pain is growing worldwide. Recent studies recapitulate the requirement for AMPA receptor in excitatory synaptic plasticity underlying pain-related syndromes. Netrin-1 and its receptor deleted in colorectal cancer (DCC) are fundamental for AMPA receptor dependent synaptic transmission. Phosphatidylinositol 4-kinase IIa (Pi4KIIa) mediates post-synaptic insertion of AMPA receptor in neuropathic disorders. This study investigates whether netrin-1 and Pi4KIIa regulate peripheral nerve injury-induced neuropathic pain. ⋯ Our current results demonstrate the contribution of spinal netrin-1 and DCC in modulating the expression of Pi4KIIa in the pathogenesis of neuropathic pain in mice.