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Huang P.,Huazhong University of Science and Technology | Li C.,Huazhong University of Science and Technology | Fu T.,Huazhong University of Science and Technology | Zhao D.,Huazhong University of Science and Technology | And 7 more authors.
Behavioural Brain Research | Year: 2015

Chronic restraint stress (CRS) causes hippocampal neurodegeneration and hippocampus-dependent cognitive deficits. Flupirtine represents neuroprotective effects and we have previously shown that flupirtine can protect against memory impairment induced by acute stress. The present study aimed to investigate whether flupirtine could alleviate spatial learning and memory impairment and hippocampal apoptosis induced by CRS. CRS mice were restrained in well-ventilated Plexiglass tubes for 6. h daily beginning from 10:00 to 16:00 for 21 consecutive days. Mice were injected with flupirtine (10. mg/kg and 25. mg/kg) or vehicle (10% DMSO) 30. min before restraint stress for 21 days. After stressor cessation, the spatial learning and memory, dendritic spine density, injured neurons and the levels of Bcl-2, Bax, p-Akt, p-GSK-3β, p-Erk1/2 and synaptophysin of hippocampal tissues were examined. Our results showed that flupirtine significantly prevented spatial learning and memory impairment induced by CRS in the Morris water maze. In addition, flupirtine (10. mg/kg and 25. mg/kg) treatment alleviated neuronal apoptosis and the reduction of dendritic spine density and synaptophysin expression in the hippocampal CA1 region of CRS mice. Furthermore, flupirtine (10. mg/kg and 25. mg/kg) treatment significantly decreased the expression of Bax and increased the p-Akt and p-GSK-3β, and flupirtine (25. mg/kg) treatment up-regulated the p-Erk1/2 in the hippocampus of CRS mice. These results suggested that flupirtine exerted protective effects on the CRS-induced cognitive impairment and hippocampal neuronal apoptosis, which is possibly associated with the activation of Akt/GSK-3β and Erk1/2 signaling pathways. © 2015 Elsevier B.V. Source


Xiong Q.-J.,Huazhong University of Science and Technology | Hu Z.-L.,Huazhong University of Science and Technology | Wu P.-F.,Huazhong University of Science and Technology | Ni L.,Huazhong University of Science and Technology | And 8 more authors.
American Journal of Physiology - Cell Physiology | Year: 2012

Acidsensing ion channels (ASICs) have been reported to play a role in the neuronal dopamine pathway, but the exact role in neurotransmitter release remains elusive. Human neuroblastoma SH-SY5Y is a dopaminergic neuronal cell line, which can release monoamine neurotransmitters. In this study, the expression of ASICs was identified in SH-SY5Y cells to further explore the role of ASICs in vesicular release stimulated by acid. We gathered evidence that ASICs could be detected in SH-SY5Y cells. In whole cell patch-clamp recording, a rapid decrease in extracellular pH evoked inward currents, which were reversibly inhibited by 100 μM amiloride. The currents were pH dependent, with a pH of half-maximal activation (pH 0.5) of 6.01 ± 0.04. Furthermore, in calcium imaging and FM 1-43 dye labeling, it was shown that extracellular protons increased intracellular calcium levels and vesicular release in SH-SY5Y cells, which was attenuated by PcTx1 and amiloride. Interestingly, N-type calcium channel blockers inhibited the vesicular release induced by acidification. In conclusion, ASICs are functionally expressed in SH-SY5Y cells and involved in vesicular release stimulated by acidification. N-type calcium channels may be involved in the increase in vesicular release induced by acid. Our results provide a preliminary study on ASICs in SH-SY5Y cells and neurotransmitter release, which helps to further investigate the relationship between ASICs and dopaminergic neurons. © 2012 the American Physiological Society. Source


Li C.,Huazhong University of Science and Technology | Huang P.,Huazhong University of Science and Technology | Lu Q.,Huazhong University of Science and Technology | Lu Q.,The Key Laboratory for Drug Target Researches and Pharmacodynamic Evaluation of Hubei Province | And 5 more authors.
Neuroscience | Year: 2014

Spatial memory retrieval and hippocampal long-term potentiation (LTP) are impaired by stress. KCNQ/Kv7 channels are closely associated with memory and the KCNQ/Kv7 channel activator flupirtine represents neuroprotective effects. This study aims to test whether KCNQ/Kv7 channel activation prevents acute stress-induced impairments of spatial memory retrieval and hippocampal LTP. Rats were placed on an elevated platform in the middle of a bright room for 30. min to evoke acute stress. The expression of KCNQ/Kv7 subunits was analyzed at 1, 3 and 12. h after stress by Western blotting. Spatial memory was examined by the Morris water maze (MWM) and the field excitatory postsynaptic potential (fEPSP) in the hippocampal CA1 area was recorded in vivo. Acute stress transiently decreased the expression of KCNQ2 and KCNQ3 in the hippocampus. Acute stress impaired the spatial memory retrieval and hippocampal LTP, the KCNQ/Kv7 channel activator flupirtine prevented the impairments, and the protective effects of flupirtine were blocked by XE-991 (10,10-. bis(4-Pyridinylmethyl)-9(10. H)-anthracenone), a selective KCNQ channel blocker. Furthermore, acute stress decreased the phosphorylation of glycogen synthase kinase-3β (GSK-3β) at Ser9 in the hippocampus, and flupirtine inhibited the reduction. These results suggest that the KCNQ/Kv7 channels may be a potential target for protecting both hippocampal synaptic plasticity and spatial memory retrieval from acute stress influences. © 2014 IBRO. Source


Luo Y.,Huazhong University of Science and Technology | Wu P.-F.,Huazhong University of Science and Technology | Wu P.-F.,Key Laboratory of Neurological Diseases HUST | Wu P.-F.,The Key Laboratory for Drug Target Researches and Pharmacodynamic Evaluation of Hubei Province | And 14 more authors.
CNS Neuroscience and Therapeutics | Year: 2014

Aims: Epileptic seizures are well-known neurological complications following stroke, occurring in 3% of patients. However, the intrinsic correlation of seizures with stroke remains largely unknown. Hydrogen sulfide (H2S) is a gas transmitter that may mediate cerebral ischemic injury. But the role of H2S in seizures has not been understood yet. We examined the effect of H2S on seizure-like events (SLEs) and underlying mechanisms. Methods and Results: Pentylenetetrazole (PTZ)- and pilocarpine-induced rat epileptic seizure models were tested. Low-Mg2+/high-K+- and 4-aminopyridine (4-AP)-induced epileptic seizure models were examined using patch-clamp recordings in brain slices. It was found that NaHS aggravated both PTZ- and pilocarpine-induced SLEs in rats, while both low-Mg2+/high-K+- and 4-AP-induced SLEs were also exacerbated by NaHS in brain slices, which may be due to its regulation on the voltage-gated sodium channel, N-methyl-D-aspartic acid receptor (NMDAR), and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) function. Furthermore, these effects were reversed by blocking voltage-gated sodium channel, NMDAR, and AMPAR. Conclusions: These results suggest a pathological role of increased H2S level in SLEs in vivo and in vitro. Enzymes that control H2S biosynthesis could be interesting targets for antiepileptic strategies in poststroke epilepsy treatment. © 2014 John Wiley & Sons Ltd. Source


Zhang J.-Q.,Huazhong University of Science and Technology | Wu P.-F.,Huazhong University of Science and Technology | Long L.-H.,Huazhong University of Science and Technology | Long L.-H.,Key Laboratory of Neurological Diseases HUST | And 14 more authors.
Journal of Nutritional Biochemistry | Year: 2013

Background and Purpose: Impairment of glucose utilization contributes to neuronal degeneration of Alzheimer's disease patients. Cellular glucose utilization can be regulated by calcium-dependent signaling pathways. Resveratrol (RSV) is a plant-derived polyphenol with multiple beneficial effects, including neuroprotection and metabolic improvement. Here, we investigated the effect of RSV on neuronal calcium signal and glucose utilization. Experimental Methods: Primary culture of cortical neurons, calcium imaging, 2-NBDG assay and western blotting were employed to investigate RSV-mediated effects on neuronal calcium signal and glucose utilization. Results: RSV elevated intracellular calcium in cortical neurons via modulation of secondary messenger system including nitrous oxide, cGMP and cAMP. Secondarily, a calcium-dependent enhancement of neuronal glucose utilization after RSV treatment was observed. The effects on neuronal glucose utilization are largely dependent on RSV-induced calcium-dependent AMP-activated protein kinase activation. Conclusion: Our findings show that activation of calcium-dependent signaling pathways by RSV may convey improvements of neuronal glucose utilization. © 2013 Elsevier Inc. Source

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