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| http://purl.uniprot.org/citations/24067915 | http://www.w3.org/2000/01/rdf-schema#comment | "Rett syndrome (RTT) is a neurodevelopmental disorder with symptoms starting 6-18 mo after birth, while what underlies the delayed onset is unclear. Allopregnanolone (Allop) is a metabolite of progesterone and a potent modulator of GABAA-ergic currents whose defects are seen in RTT. Allop changes its concentration during the perinatal period, which may affect central neurons via the GABAA-ergic synaptic transmission, contributing to the onset of the disease. To determine whether Mecp2 disruption affects Allop modulation, we performed studies in brain slices obtained from wild-type (WT) and Mecp2(-/Y) mice. Allop dose dependently suppressed locus coeruleus (LC) neuronal excitability in WT mice, while Mecp2-null neurons showed significant defects. Using optogenetic approaches, channelrhodopsin was specifically expressed in GABA-ergic neurons in which optical stimulation evoked action potentials. In LC neurons of WT mice, Allop exposure increased the amplitude of GABAA-ergic inhibitory postsynaptic currents (IPSCs) evoked by optical stimulation and prolonged the IPSC decay time. Consistently, Allop augmented both frequency and amplitude of GABAA-ergic spontaneous IPSCs (sIPSCs) and extended the decay time of sIPSCs. The Allop-induced potentiation of sIPSCs was deficient in Mecp2(-/Y) mice. Surprisingly, the impairment occurred at 3 wk postnatal age, while no significant difference in Allop modulation was observed in 1-2 wk between WT and Mecp2(-/Y) mice. These results indicate that the modulation of GABAA-ergic synaptic transmission by Allop is impaired in LC neurons of Mecp2-null mice at a time when RTT-like symptoms manifest, suggesting a potential mechanism for the delayed onset of the disease."xsd:string |
| http://purl.uniprot.org/citations/24067915 | http://purl.org/dc/terms/identifier | "doi:10.1152/ajpcell.00195.2013"xsd:string |
| http://purl.uniprot.org/citations/24067915 | http://purl.uniprot.org/core/author | "Jiang C."xsd:string |
| http://purl.uniprot.org/citations/24067915 | http://purl.uniprot.org/core/author | "Zhong W."xsd:string |
| http://purl.uniprot.org/citations/24067915 | http://purl.uniprot.org/core/author | "Jin X."xsd:string |
| http://purl.uniprot.org/citations/24067915 | http://purl.uniprot.org/core/date | "2013"xsd:gYear |
| http://purl.uniprot.org/citations/24067915 | http://purl.uniprot.org/core/name | "Am J Physiol Cell Physiol"xsd:string |
| http://purl.uniprot.org/citations/24067915 | http://purl.uniprot.org/core/pages | "C1151-60"xsd:string |
| http://purl.uniprot.org/citations/24067915 | http://purl.uniprot.org/core/title | "Time-dependent modulation of GABA(A)-ergic synaptic transmission by allopregnanolone in locus coeruleus neurons of Mecp2-null mice."xsd:string |
| http://purl.uniprot.org/citations/24067915 | http://purl.uniprot.org/core/volume | "305"xsd:string |
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