-
[show abstract]
[hide abstract]
ABSTRACT: Acid-sensing ion channel-1a (ASIC1a) is localized in brain regions with high synaptic density and is thought to contribute to synaptic plasticity, learning, and memory. A prominent hypothesis is that activation of postsynaptic ASICs promotes depolarization, thereby augmenting N-methyl-d-aspartate receptor function and contributing to the induction of long-term potentiation (LTP). However, evidence for activation of postsynaptic ASICs during neurotransmission has not been established. Here, we re-examined the role of ASIC1a in LTP in the hippocampus using pharmacological and genetic approaches. Our results showed that a tarantula peptide psalmotoxin, which profoundly blocked ASIC currents in the hippocampal neurons, had no effect on LTP. Similarly, normal LTP was robustly generated in ASIC1a-null mice. A further behavioral analysis showed that mice lacking ASIC1a had normal performance in hippocampus-dependent spatial memory. In summary, our results indicate that ASIC1a is not required for hippocampal LTP and spatial memory. We therefore propose that the role of ASIC1a in LTP and spatial learning should be reassessed.
Journal of Neuroscience 01/2013; 33(5):1828-1832. · 7.11 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: GABAergic signaling in hippocampal pyramidal neurons undergoes a switch from depolarizing to hyperpolarizing during early neuronal development. Whether such a transformation of GABAergic action occurs in dentate granule cells (DGCs), located at the first stage of the hippocampal trisynaptic circuit, is unclear. Here, we use noninvasive extracellular recording to monitor the effect of synaptically released GABA on the DGC population. We find that GABAergic responses in adolescent and adult rat DGCs are still depolarizing from rest. Using a morphologically realistic DGC model, we show that GABAergic action, depending on its precise timing and location, can have either an excitatory or inhibitory role in signal processing in the dentate gyrus.
Journal of Neuroscience 01/2012; 32(1):62-7. · 7.11 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Astrocytes function as spatial K(+) buffers by expressing a rich repertoire of K(+) channels. Earlier studies suggest that acid-sensitive tandem-pore K(+) channels, mainly TWIK-related acid-sensitive K(+) (TASK) channels, mediate part of the passive astroglial membrane conductance. Here, using a combination of electrophysiology and pharmacology, we investigated the presence of TASK-like conductance in hippocampal astrocytes of rat brain slices. Extracellular pH shifts to below 7.4 (or above 7.4) induced a prominent inward (or outward) current in astrocytes in the presence of tetrodotoxin, a Na(+) channel blocker, and 4,4'-diisothiocyanatostilbene-2,2'-disulfonate, a co-transporter blocker. The pH-sensitive current was insensitive to quinine, a potent blocker of tandem-pore K(+) channels including TWIK-1 and TREK-1 channels. Voltage-clamp analysis revealed that the pH-sensitive current exhibited weak outward rectification with a reversal potential of -112 mV, close to the Nernst equilibrium potential for K(+) . Furthermore, the current-voltage relationship was well fitted with the Goldman-Hodgkin-Katz current equation for the classical open-rectifier 'leak' K(+) channel. The pH-sensitive K(+) current was potentiated by TASK channel modulators such as the volatile anesthetic isoflurane but depressed by the local anesthetic bupivacaine. However, unlike TASK channels, the pH-sensitive current was insensitive to Ba(2+) and quinine. Thus, the molecular identity of the pH-sensitive leak K(+) channel is unlikely to be attributable to TASK channels. Taken together, our results suggest a novel yet unknown leak K(+) channel underlying the pH- and anesthetic-sensitive background conductance in hippocampal astrocytes.
European Journal of Neuroscience 09/2010; 32(5):725-35. · 3.63 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: NG2 cells, a fourth type of glial cell in the mammalian CNS, undergo reactive changes in response to a wide variety of brain insults. Recent studies have demonstrated that neuronally expressed acid-sensing ion channels (ASICs) are implicated in various neurological disorders including brain ischemia and seizures. Acidosis is a common feature of acute neurological conditions. It is postulated that a drop in pH may be the link between the pathological process and activation of NG2 cells. Such postulate immediately prompts the following questions: Do NG2 cells express ASICs? If so, what are their functional properties and subunit composition? Here, using a combination of electrophysiology, Ca2+ imaging and immunocytochemistry, we present evidence to demonstrate that NG2 cells of the rat hippocampus express high density of Ca2+-permeable ASIC1a channels compared with several types of hippocampal neurons. First, nucleated patch recordings from NG2 cells revealed high density of proton-activated currents. The magnitude of proton-activated current was pH dependent, with a pH for half-maximal activation of 6.3. Second, the current-voltage relationship showed a reversal close to the equilibrium potential for Na+. Third, psalmotoxin 1, a blocker specific for the ASIC1a channel, largely inhibited proton-activated currents. Fourth, Ca2+ imaging showed that activation of proton-activated channels led to an increase of [Ca2+]i. Finally, immunocytochemistry showed co-localization of ASIC1a and NG2 proteins in the hippocampus. Thus the acid chemosensor, the ASIC1a channel, may serve for inducing membrane depolarization and Ca2+ influx, thereby playing a crucial role in the NG2 cell response to injury following ischemia.
PLoS ONE 01/2010; 5(9). · 4.09 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: We present a case of paradoxical gas embolism during CO2 insufflation in laparoscopic nephrectomy for a huge renal angiomyolipoma. Paradoxical CO2 embolism in the left heart chambers without demonstrable intracardiac right-to-left shunt was detected by transesophageal echocardiography (TEE). The surgical procedure was stopped immediately, but the patient recovered with mild neurologic deficit. We speculate that rapid pneumoperitoneum introduction pushed CO2 into the abnormal vasculature of the angiomyolipoma, which communicates with the systemic vascular system, causing pseudoaneurysm formation. Follow-up abdominal computed tomography showed a new pseudoaneurysm inside the tumor. If intracardiac right-to-left shunt is excluded for the reason of paradoxical gas existence, there remains extracardiac right-to-left shunt, with transpulmonary passage of the venous emboli being the most likely mechanism. In fact, the cause of paradoxical gas embolism in this case remains unknown. Therefore, laparoscopic surgery for huge angiomyolipoma should be performed with extreme caution; an open procedure may be considered as an alternative.
Journal of the Chinese Medical Association 05/2008; 71(4):214-7. · 0.79 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Desipramine (DP) is a tricyclic antidepressant used for treating depression and numerous other psychiatric disorders. Recent studies have shown that DP can promote neurogenesis and improve the survival rate of hippocampal neurons. However, whether DP induces neuroprotection or promotes the differentiation of neural stem cells (NSCs) needs to be elucidated. In this study, we cultured NSCs derived from the hippocampal tissues of adult rats as an in vitro model to evaluate the modulation effect of DP on NSCs. First, we demonstrated that the expression of Bcl-2 mRNA and nestin in 2 microM DP-treated NSCs were up-regulated and detected by real-time reverse transcriptase polymerase chain reaction (RT-PCR). The results of Western blotting and immunofluorescent study confirmed that Bcl-2 protein expression was significantly increased in Day 3 DP-treated NSCs. Using the Bcl-2 small interfering RNA (siRNA) method, our results further showed that DP protects the lipopolysaccharide (LPS)-induced apoptosis in NSCs, in part by activating the expression of Bcl-2. Furthermore, DP treatment significantly inhibited the induction of proinflammatory factor interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha in the culture medium of LPS-treated NSCs mediated by Bcl-2 modulation. The results of high performance liquid chromatography coupled to electrochemical detection further confirmed that DP significantly increased the functional production of serotonin (26+/-3.5 microM, DP-treated 96 h) and noradrenaline (50+/-8.9 microM, DP-treated 96 h) in NSCs through activation of the MAPK/ERK pathway and partially mediated by Bcl-2. In conclusion, the present results indicate that DP can increase neuroprotection ability by inhibiting the LPS-induced inflammatory process in NSCs via the modulation of Bcl-2 expression, as confirmed by the siRNA method.
Journal of Pharmacological Sciences 06/2007; 104(1):61-72. · 2.08 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: In recent years, the incidences of stomach and colon cancers have ranked within the top fives of all malignancies in Taiwan. To say healthwise, regular gastrointestinal (GI) endoscopic examinations are recommended, as they are the best way for early detection. However, unpleasantness of and terrible experience from the examination greatly discourage the acceptance of many people even of the suspected groups. Now, the administration of sedative or analgesic to achieve the so called "conscious sedation" during GI endoscopy which brings about better tolerability and improves general acceptance offers a more satisfactory service. In this article, the related issues about preprocedure evaluation, preparation, medications and complications of conscious sedation in GI endoscopy are discussed after review.
Acta Anaesthesiologica Taiwanica 04/2005; 43(1):33-8.
-
[show abstract]
[hide abstract]
ABSTRACT: Intracranial hemorrhage (ICH) from an arteriovenous malformation (AVM) in pregnancy is quite rare and could lead to exceedingly high maternal and fetal morbidity and mortality. We report a 26-year-old woman at 36 weeks' gestation who sustained ICH due to two huge AVMs. For preventing from progressive increased intracranial pressure (IICP), Cesarean section under general anesthesia was performed successfully. Herein, we also discuss the anesthetic management after reviewing the related current literatures.
Acta anaesthesiologica Sinica 01/2004; 41(4):209-14.
-
[show abstract]
[hide abstract]
ABSTRACT: Homocystinuria is an autosomal recessive disease with multiple systemic disorders. Here we report a 15-year-old lad suffering from homocystinuria who required an ocular surgery including lentectomy and implant of plastic lens, OS and anterior retinal cryotherapy, OD under general anesthesia because of lens subluxation and lattice degeneration. It is the elective ocular procedure most commonly performed for homocystinuric children. Proper precautions should be taken during anesthetic management since this condition inspires some particular anesthetic complications that could be prevented by careful consideration and understanding of its pathophysiology. Providentially our patient stood the operation well and was discharged without subsequent thromboembolism or other complication as an aftermath.
Acta anaesthesiologica Sinica 10/2002; 40(3):153-6.
