Our study suggests that increased CSF leptin, likely from blood-brain barrier breakdown, combined with elevated serum GH and IGF-1 after TBI, leads to accelerated fracture healing.
The effects of stresscopin (SCP) on rat paraventricular nucleus (PVN) neurons were examined using whole-cell patch-clamp recordings and single-cell reverse-transcription multiplex polymerase chain reaction (SC-RT-mPCR) techniques. Under current-clamp conditions, bath application of SCP (100 nM) induced inhibition in 35.2% (37/105) of putative magnocellular neurons and 24.7% (20/81) of putative parvocellular neurons, and excitation in 5.7% (6/105) of putative magnocellular neurons and 18.5% (15/81) of putative parvocellular neurons. SCP-induced inhibition persisted in the presence of a mixture of TTX, a voltage-gated Na+ channel blocker, CNQX, an AMPA/kainate receptor antagonist and bicuculline, a GABAA receptor antagonist, whereas SCP-induced excitation of PVN neurons was reversed by the mixture. The SCP-induced inhibition of PVN neurons was abolished by bath application of antisauvagine-30, a selective CRF receptor 2 (CRF-R2) antagonist. Under voltage-clamp conditions, SCP evoked outward currents at the holding potential (−60 mV), which reversed near the potassium equilibrium potential. The SCP-evoked membrane currents were completely blocked by bath application of tertiapin-Q, a selective blocker of G protein-activated inwardly rectifying potassium (GIRK) channels. SC-RT-mPCR analysis indicated that all the SCP-sensitive PVN neurons (57 SCP-inhibited neurons, 21 SCP-excited neurons) expressed CRF-R1 and CRF-R2 mRNAs. Among SCP-hyperpolarized PVN neurons, oxytocin (OT) mRNA was detected in 91.8% of putative magnocellular neurons and 45.0% of putative parvocellular neurons. OT mRNA was also detected in 26.6% of SCP-depolarized parvocellular neurons, but not in SCP-depolarized magnocellular neurons. These results indicate that SCP inhibits a subpopulation of PVN neurons, especially OTergic magnocellular neurons, by enhancing the activity of GIRK channels via CRF-R2.
Etomidate (ET) produces sedation by binding on the γ-aminobutyric acid type A (GABAA) receptors. We previously found that ET inhibited cerebellar Purkinje cells activity via both GABAA and glycine receptors in vivo in mice, suggesting that ET modulated sensory information synaptic transmission in cerebellar cortex. In this study, we investigated the effect of ET on the sensory stimulation-evoked responses in the cerebellar granule layer (GL) in urethane-anesthetized mice, using electrophysiological and pharmacological methods. Our results showed that cerebellar surface perfusion of ET (100 μmol/L) significantly decreased amplitude and area under the curve (AUC) of the sensory stimulation-evoked excitatory component (N1) in the cerebellar GL. Application of GABAA receptor antagonist, SR95531 (20 μmol/L) significantly attenuated, but not abolished the ET-induced decrease in amplitude and AUC of facial stimulation-evoked responses. However, application of a mixture of SR95531 (20 μmol/L) and cannabinoid 1 receptor (CB1) antagonist, AM-251 (5 μmol/L), completely blocked the ET-induced decrease in amplitude and AUC of facial stimulation-evoked responses. Furthermore, application of the CB1 receptor agonist, WIN55212-2, induced a decrease in amplitude and AUC of N1 in the absence of GABAA receptors activity, as well occluded the ET-induced depression of N1. Moreover, the ET-induced changes in amplitude and AUC of N1 in absence of GABAA receptors activity were abolished by a specific protein kinase A (PKA) inhibitor, KT5720. These results indicate that ET facilitates CB1 receptors in the absence of GABAA receptors activity, resulting in a depression of the sensory stimulation-evoked synaptic transmission via PKA signaling pathway in mouse cerebellar GL.
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