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Effects of Melatonin on Levels of Glutamate, Gaba and Their Receptors in Hippocampus of Rats with Seizures Induced by Glutamate

Author: WangCongRong
Tutor: ZhouHouLun
School: Huazhong University of Science and Technology
Course: Human Anatomy
Keywords: Melatonin Epilepsy Glutamate GluR2 γ-aminobutyric acid GABR
CLC: R742.1
Type: Master's thesis
Year: 2007
Downloads: 117
Quote: 0
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Abstract

Epilepsy (Epilepsy) is a common and frequently-occurring disease of the central nervous system, which is the result of repeated paroxysmal excessive discharge of the neurons. Currently epilepsy incidence of central nervous system - immune - endocrine network regulation imbalance is closely related to neural mechanisms, immune and endocrine factors in receptor and its messenger and gene level adjustment. Which the brains of patients with epilepsy excitatory system suppression system out of balance is the main neural mechanisms of seizures. Glutamic acid (Glutamate, Glu) is an excitatory neurotransmitter in the central nervous system, is widely distributed in the cerebral cortex, cerebellum, basal nucleus and other parts of the nervous system. A large number of studies have shown the Glu to participate in the formation of epilepsy, while Glu can also serve as an epileptogenic agent used in the production of animal models of experimental epilepsy. The mechanism may promote seizures Glu combined with Glu receptor neurons, mediated G protein uncoupling ion channels, or a combination of excitatory amino acid receptors (NMDA-type), resulting in a large number of Ca2 and Na within flow, K, Mg2 outflow, resulting in depolarization caused seizures. The Glu receptor ionotropic glutamate receptors (ionotropic glutamate receptors, iGluRs) and metabotropic glutamate receptors (metabotropic glutamate receptors, metabotropic glutamate receptors in) ionotropic glutamate receptors, including the NMDA receptor, AMPA receptor and KA receptors; GluR2 four subtypes of glutamate AMPA receptors (GluR1-4) in one of the main features of the AMPA receptors determined by GluR2 Glutamate Receptor GluR2 Subunit Expression of cut is considered to be a molecule switch control glutamate receptor AMPA Ca2 permeability blocking or reduce Glu excitotoxicity, thus affecting the seizures. γ-amino butyric acid (γ-aminobutyric-acid, GABA) is the most important inhibitory neurotransmitter in the central nervous system. Epilepsy animal experimental studies have shown that decreased GABA content in the cerebral cortex of epileptic animals and reduce the extent and degree of seizures consistent. The intracisternal injection GABA can suppress seizures in experimental animals, intraperitoneal or intravenous drug-induced epilepsy GABA also against animals. Cerebrospinal fluid (CSF) in the the GABA content epilepsy threshold was positively correlated with CSF GABA decreased its low seizure threshold, prone to epilepsy. GABA mainly ionotropic receptors (GABRA GABRC), and metabotropic receptors (GABRB) play an inhibitory function, GABRA receptor class of chemical-gated ion channel receptor is mainly distributed in the central neurons and peripheral sympathetic neurons suddenly Aftertouch membranes, GABA and other agonists bind can cause the postsynaptic membrane chloride channel to open, a large number of chloride ions flow, membrane hyperpolarization, the formation of the inhibitory postsynaptic potential (IPSP) mediated by GABA postsynaptic inhibition effect. Melatonin (melatonin, MT), chemical name is N-acetyl-5 - methoxytryptamine is a major by the hypothalamus pineal cell synthesis and secretion of indole-neural endocrine hormones. The secretion showed obvious high regularity, studies have shown that MT has a wide range of physiological effects, can maintain the circadian rhythm, promote sleep, enhance immune function, inhibit tumor cell growth, and growth, development, sexual function, and many of the day and low night The organ played a role in regulating. In recent years, with the deepening of the MT function of the MT Other important features are starting to be found, including the removal of free radicals, antioxidant, neuroprotective and anticonvulsant role in inhibiting seizures. But now, not many studies about the MT suppress epileptic mechanism of action. Studies have shown that the MT may play its anticonvulsant by the specificity MT receptor on the cell membrane, inhibition of epilepsy action, the the MT membrane receptor competitive antagonist Luzindole capable of blocking the MT anticonvulsant inhibit the role of epilepsy. This study was designed by observing MT school Glu epileptogenic rat behavior, but the effect of the hippocampus Glu and its receptor GluR2 and GABA and its receptor GABRA1 of the preliminary study of the mechanism of action of MT suppressing epileptic. The experiment is divided into two parts. The first part, 40 healthy male SD rats were randomly divided into four groups (n = 10), respectively, in group A: saline control group; group B: MT Glu group; C group: Glu epileptogenic group; group D: Luzindole MT Glu group. Observe and record behavioral changes in rats using immunohistochemical methods to detect changes in the rat hippocampus Glu and its receptor the GluR2 content in the. A group without epileptic seizures and epileptiform discharges no or only mild seizures (0 ~ Ⅱ grade) group B, C and D groups epileptic seizures (Ⅲ ~ Ⅴ grade); immunohistochemical analysis results. hippocampal CA1-CA3 pyramidal cell layer of the dentate gyrus granule cell layer neurons were expressed. Glu the cytoplasm coloring, C and D groups than Group A districts immunoreactivity significantly increased in group B compared with group C and D the number of positive cells decreased, cells staining shallow, significant differences (P lt; 0.05), group B no significant differences compared to group A; darker coloring of Glutamate Receptor GluR2 Subunit membrane, C and D groups significantly decreased compared with group A District immunoreactivity B group than in Group C and Group D the number of positive cells increased significantly different (P lt ; 0.05) in group B and group A compared with no significant differences. The results suggest that MT against glutamate induced epileptic rats epileptiform seizures degree of epileptiform discharges can inhibit one of the mechanisms to reduce the expression of Glu via specific membrane receptor, to reduce the activity of Glu and raised the GluR2 expression then play the suppression epileptic effect. The second part, 40 healthy male SD rats were randomly divided into four groups (n = 10), respectively, in group A: saline control group; group B: MT Glu group; C group: Glu epileptogenic group; D Group : Luzindole MT Glu group. Observe and record behavioral changes in rats using immunohistochemical methods to detect changes in the rat hippocampus the GABA its receptor GABRA1 to content. A group without epileptic seizures and epileptiform discharges no or only mild seizures (0 ~ Ⅱ grade) group B, C and D groups epileptic seizures (Ⅲ ~ Ⅴ grade); immunohistochemical analysis results. hippocampal CA1-CA3 pyramidal cell layer of the dentate gyrus granule cell layer neurons were expressed. The GABA membrane cytoplasmic colored, coloring deeper GABRA1 membrane, C and D groups than Group A districts immunoreactivity was significantly diminished, the number of positive cells was significantly reduced cell staining shallow. Significantly enhanced the District immune reactivity of group B than in group C and group D, the number of positive cells was significantly increased, deeply stained cells, significant differences were statistically significant (P lt; 0.05). Group B and group A was not significantly different. The results show that the MT against glutamate induced epileptic rats epileptiform seizures degree of epileptiform discharges can inhibit one of the mechanisms through its specific membrane receptors, enhanced the the hippocampal inhibitory neurotransmitter GABA and its receptor GABRA1 activity and expression, and thus exert its effect. In summary, MT inhibiting antiepileptic effect and its mechanism of action may be involved through its specific membrane receptors reduce Glu express their excitement activity and raised GluR2 expression, enhance GABA receptor GABRA1 expression and its suppression activity, and then play the effect to suppress seizures.

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