The role and the mechanism of γ-aminobutyric acid during central nervous system development

γ-aminobutyric acid （GABA） is an inhibitory neurotransmitter in adult mammalian central nervous system （CNS）. During CNS development, the role of GABA is switched from an excitatory transmitter to an inhibitory transmitter, which is caused by an inhibition of calcium influx into postsynaptic neuron derived from release of GABA. The switch is influenced by the neuronal chloride concentration. When the neuronal chloride concentration is at a high level, GABA acts as an excitatory neurotransmitter. When neuronal chloride concentration decreases to some degree, GABA acts as an inhibitory neurotransmitter. The neuronal chloride concentration is increased by Na^＋-K^＋-Cl^-Cl^- cotransporters 1 （NKCC 1）, and decreased by K^＋-Cl^- cotransporter 2 （KCC2）.

A Woman with Psychogenic Non-epileptic Seizures and Pelvic Mass

MOST cases of encephalitis are caused by viruses but a few have an immunological basis, such as paraneoplastic encephalitis, with specific antibodies identified. One recently characterized encephalitis caused by antibodies is anti-N- methyl-D-aspartate （NMDA） receptor encephalitis. It is a form of paraneoplastic limbic encephalitis associated with ovarian teratoma and has recently been described.The NMDA receptor mediates excitatory neurotransmission. It is important for synaptic plasticity, and thus for higher function such as learning and memory. This disorder results in prominent psychiatric symptoms followed by a rapid decline of the level of consciousness, central hypoventilation, seizures, involuntary movements and dysautonomia.

基于突触离子通道动力学神经元网络的高效并行仿真算法

在计算神经科学领域,大规模神经元网络的并行仿真对探索和揭示生物大脑中信息传递机制有着重要作用。为加速大规模神经元网络仿真,提出一种模块独立性强、耦合度低的基于突触递质-受体离子通道动力学的神经元网络的并行算法。通过分析化学突触信息传递机理及递质分子、受体离子通道动力学特征,提出了递质-受体计算分离的思想,增强了突触前神经元引起的递质分子浓度计算与突触后绑定状态的受体浓度计算之间的独立性,降低突触电流计算中突触前神经元状态和突触后神经元状态之间的耦合度。基于上述思想,设计并实现了一种生物神经网络并行算法。仿真结果表明了该算法的高效性。

Interaction of δ-opioid Receptor with Membrane Transporters: Possible Mechanisms in Pain Suppression by Acupuncture

Objective： To investigate the possible mechanisms in acupuncture analgesia by interaction of δ-opioid receptor with neurotransmitter transport proteins or the Na^＋-K^＋ pump. Methods： Microinjection of respective heterologous cRNA into the Xenopus oocytes as a model system, and measurement of steady-state currents under two-electrode voltage clamp. Results： The co-expression of the 8-opioid receptor with GAT1, EAAC 1 or the sodium pump resulted in reducing activity of the respective transporter. Opioid receptor activation affected transporter activity in different ways： 1） GAT1 was further inhibited; 2） EAAC1 was stimulated; 3） Na^＋-K^＋ pump activity interfered with agonist sensitivity of DOR. Pump inhibition led to higher sensitivity for DPDPE. Conclusion： GABA transporter inhibition and glutamate transporter stimulation may counteract pain sensation by affecting the neurotransmitter concentration in the synaptic cleft and, therefore, may contribute synergistically to pain suppression by acupuncture. Sodium pump inhibition by endogenous ouabain may amplify these effects. These synergistic effects may be the molecular mechanism of inhibiting pain sense and/or acupuncture analgesia.

The effects of pinellia total alkaloids on the amino acid concentration and the GABAA receptor expression in hippocampus region of epileptic rats

The antiepileptic effect of pinellia total alkaloids（PTA） on penicillin（PNC） chronically kindled rats was investigated. We investigated the effects of PTA on Glu,Asp,Gly andγ-aminobutyric acid（GABA） concentrations and the expression level of cerebral GABA_A receptor in hippocampus.The influence of PTA on epilepsy seizure latency and degree in PNC chronically kindled rats were observed.High performance liquid chromatography（HPLC） was adopted to measure the concentrations of Glu, Asp,Gly and GABA in hippocampus. Reverse transcriptase-polymerase chain reaction （RT-PCR） was used to determine the expression of cerebral GABAA receptor mRNA. Compared with normal rats, the levels of GABA and Gly decreased obviously while the level of Glu and Asp increased significantly in model rats. The cerebral GABAA receptor mRNA level was also decreased at the same time. The difference was statistically different compared to the control group. PTA could prolong the latent period of the penicillin induced seizure and weaken the extent of seizure, compared with the model group without PTA treatment. Moreover, PTA increased the level of GABA and the expression level of GABAA receptor, while decreased the level of Glu significantly. However, it had no obvious effect on the level of Gly and Asp. Pre-treatment of PTA can also increase the GABAA receptor mRNA level. In conclusion, PTA could alleviate the PNC chronically kindled rat seizure. It increased the GABA level and the expression of GABAA receptor, and it decreased the Glu concentration.

Effects of free radicals and amyloid β protein on the currents of expressed rat receptors in Xenopus oocytes

Objective To investigate the effects of free radicals (FRs) and amyloid β protein 1 40 (Aβ 1 40 ) on the functions of expressed neurotransmitter receptors (NRs) in Xenopus oocytes Methods Total RNA and messenger RNA (mRNA) was prepared from 3 month old Wistar rat brain tissues with Promega kits and microinjected into maturated Xenopus oocytes (stages Ⅴ Ⅵ) with 50?nl (50?ng) for each oocyte The microinjected oocytes were incubated with modified Bath's solution at 19 0℃±1 0℃ for receptor expression and their currents were recorded with double electrode voltage clamp technique Superoxide anion free radicals (SAFRs) were produced via a reaction system (HPX/XO) with hypoxanthine (HPX, 0 05?mol/L) and xanthine oxidase (XO, 0 1?U/L) In order to observe the effects of Aβ and SAFRs on the expressed glutamate receptor, HPX/XO and Aβ 1 40 were added to incubation solution at 12?h, 24?h and 96?h before recording Results The results showed that the oocytes expressed functional NRs originating from rat brain tissues These NRs included muscarinic acetylcholine (mACh), glutamate (Glu), dopamine (DA), serotonin (5 HT) and γ aminobutyric acid (GABA) The current characteristics of expressed receptors were inward currents carried by chloride ion with their equibrilium potentials close to -22?mV The extent of effect on the current of expressed glutamate receptor from rat brain was different among different Aβ concentrations and incubation times Aβ 1 40 at a concentration of 20?nmol/L had little effect on the currents of expressed rat brain glutamate receptors up to 24?h of incubation period; but the currents of glutamate receptor were significantly decreased (25% off, P <0 01) in the treatment of 60?nmol/L Aβ 1 40 over 24?h Moreover, when 20?nmol/L Aβ 1 40 was co incubated over 12?h with SAFRs produced by the reaction system of HPX/XO, it was found that the currents of expressed rat brain glutamate receptors had been changed markedly When the oocytes were co treated with 60?nmol/L Aβ 1 40 and SAFRs over a period of 12?h, the currents of glutamate receptor significantly decreased (21% off, P <0 05), and the decreased percentage reached 52% over 24?h co treatment with 60?nmol/L Aβ 1 40 and SAFRs In addition, vitamin E had a partial effect against this inhibitory effect Conclusion The results suggest that Aβ has a kind of inhibitory effect upon the current of the glutamate receptor, similar to the effects of free radicals The effects can be antagonized by vitamin E These imply that Aβ may play a role via inhibiting receptor function in the pathophysiology of Alzheimer's disease

Differential effects of aging on EEG after baclofen administration

Baclofen is a selective gamma-aminobutyric acid (GABA) type B agonist that may have important medicinal uses,such as in analgesics and drug addiction treatment.In addition,evidence is accumulating that suggests GABAergic-mediated neurotransmission is altered during aging.This study investigated whether baclofen administration (5 mg kg 1) induces differential effects on cortical electrical activity with age.Electroencephalograms (EEGs) were recorded from young (3-4 months) and aged (15-17 months) rats,and both the absolute and relative powers in five frequency bands (delta:2-4 Hz;theta:4-8 Hz;alpha:8-12 Hz;beta:12-20 Hz;gamma:20-100 Hz) were analyzed.Before administration of baclofen,we found that the EEG relative power in the beta band was higher in the aged than that in the young rats.After administration of baclofen,there was a slower increase in the relative power in the delta band in the aged than that in the young rats.Moreover,there was no significant difference between the two age groups in absolute power in any frequency band.These findings indicate that baclofen treatment appears to differentially modify cortical EEG activity as a function of age.Our data further elucidate the relationship between GABA B receptor-mediated neurotransmission and aging.