Overexpression of γ-aminobutyric acid transporter subtype I leads to susceptibility to kainic acid-induced seizure in transgenic mice

Ma, Yanlin; Hu, Jia; Zhao, Wen Juan; Fei, Jian; Yu, Yun; Zhou, Xinyu; Mei, Zhanlong; Guo, Li

doi:10.1038/sj.cr.7290067

Cited by 25 publications

(24 citation statements)

References 17 publications

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“…Although still somewhat controversial, many studies have shown that the expression of AMPA-, KA-and NMDA-sensitive receptors as well as the GABA A receptor is either constant or variably diminished in many different brain regions including the hippocampus during aging (Gonzales et al, 1991;Pittaluga et al, 1993;Le Jeune et al, 1996;Nicolle et al, 1996;EcklesSmith et al, 2000;Kuehl-Kovarik et al, 2000;Magnusson, 2000;Sonntag et al, 2000;Wenk and Barnes, 2000;Adams et al, 2001;Clayton and Browning, 2001;Clayton et al, 2002;Lerma et al, 2001). Differences in a variety of other factors, including voltage-gated calcium channels (Vigues et al, 1999;Kelly et al, 2003), androgen levels (Mejias-Aponte et al, 2002;Ramsden et al, 2003;Ciriza et al, 2004), and GABA receptor function (MacGregor et al, 1997;Ma et al, 2001) which have been shown to modulate kainate-induced seizure activity in young animals, may modulate susceptibility in aged animals as well.…”

Section: Discussionmentioning

confidence: 99%

Effect of age on kainate-induced seizure severity and cell death

et al. 2008

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While the onset and extent of epilepsy increases in the aged population, the reasons for this increased incidence remain unexplored. The present study used two inbred strains of mice (C57BL/6J and FVB/NJ) to address the genetic control of age-dependent neurodegeneration by building upon previous experiments that have identified phenotypic differences in susceptibility to hippocampal seizure-induced cell death. We determined if seizure induction and seizure-induced cell death are affected differentially in young adult, mature, and aged male C57BL/6J and FVB/NJ mice administered the excitotoxin, kainic acid. Dose response testing was performed in three-four groups of male mice from each strain. Following kainate injections, mice were scored for seizure activity and brains from mice in each age group were processed for light microscopic histopathologic evaluation seven days following kainate administration to evaluate the severity of seizure-induced brain damage. Irrespective of the dose of kainate administered or the age group examined, resistant strains of mice (C57BL/6J) continued to be resistant to seizure-induced cell death. In contrast, aged animals of the FVB/NJ strain were more vulnerable to the induction of behavioral seizures and associated neuropathology after systemic injection of kainic acid than young or middle-aged mice.Results from these studies suggest that the age-related increased susceptibility to the neurotoxic effects of seizure induction and seizure-induced injury is regulated in a strain-dependent manner, similar to previous observations in young adult mice. Keywords mouse strain; excitotoxicity; kainic acid; epilepsy; cell death; aging Knowledge about the influence of aging on the susceptibility of the brain to seizure disorders is of critical importance in geriatric medicine and public health. Epilepsy is the most common neurological disorder after stroke, affecting more than 50 million persons worldwide and with a 2-3% life time risk of being given a diagnosis of epilepsy (Browne and Holmes, 2001). Currently it is well known that there is a significant incidence of epilepsy in children. However, less clearly recognized but of increasing importance is the significant incidence of epilepsy in Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript the elderly population. Recent studies in the United States and Europe indicate that the agespecific incidence of epilepsy is higher in those over the age of 65 years than in those in the first decade of life (Talli...

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Section: Discussionmentioning

confidence: 99%

Effect of age on kainate-induced seizure severity and cell death

et al. 2008

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“…Our previous study showed that homozygous GAT1 2/2 mice exhibited impaired hippocampusdependent learning and memory [18]. We also found that overexpression of GAT1 led to cognitive deterioration in transgenic mice [19]. Interestingly, the heterozygous and homozygous GAT1 knockout mice showed opposite behavioral response to some of the actions of ethanol, including locomotor stimulation, preference, and reward [17].…”

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Enhanced learning and memory in <italic>GAT1</italic> heterozygous mice

Shi¹,

Cai²,

Liu³

et al. 2012

ABBS

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g-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the central nervous system. The termination of GABA transmission is through the action of a family of membrane proteins, called GABA transporters (GAT1 -4). It is well established that GABA system is involved in the modulation of memory. Our previous study showed that homozygous GAT1 2/2 mice exhibited impaired hippocampus-dependent learning and memory. To evaluate the impact of endogenous reduced GABA reuptake on mice cognitive behaviors, the ability of learning and memory of heterozygous GAT1 1/2 mice was detected by the passive avoidance paradigm and Morris water maze. The hole board paradigm was also used to measure changes in anxiety-related behavior or exploratory behavior in such mice. As one form of synaptic plasticity, longterm potentiation was recorded in the mouse hippocampal CA1 area. We found that GAT1 1/2 mice displayed increased learning and memory, decreased anxiety-like behaviors, and highest synaptic plasticity compared with wild-type and homozygous GAT1 2/2 mice. Our results suggest that a moderate reduction in GAT1 activity causes the enhancement of learning and memory in mice.

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“…Neurotransmitter transporters play an important role in controlling of neural signal transmission, dysfunction in expression of neurotransmitter transporter genes may cause different diseases [7][8][9]. To determine if there is NET expressed in cardiac sympathetic system, RT-PCR was carried out from total RNA of rat myocardium and cardiac sympathetic ganglia.…”

Section: Resultsmentioning

confidence: 99%

Norepinephrine transporter (NET) is expressed in cardiac sympathetic ganglia of adult rat

Sun

et al. 2001

Cell Res

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The sympathetic nervous system plays a cardinal role in regulating cardiac function through releasing the neurotransmitter norepinephrine (NE). In comparison with central nervous system, the molecular mechanism of NE uptake in myocardium is not clear. In present study, we proved that in rat the CNS type of NE transporter (NET) was also expressed in middle cervical-stellate ganglion complex (MC-SG complex) which is considered to control the activity of heart, but not expressed in myocardium. The results also showed that NET expression level in right ganglion was significantly higher than in the left, rendering the greater capacity of NE uptake in right ventricle, a fact which may contribute to the maintenance of right ventricular function under pathologic state.

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Overexpression of γ-aminobutyric acid transporter subtype I leads to susceptibility to kainic acid-induced seizure in transgenic mice

Cited by 25 publications

References 17 publications

Effect of age on kainate-induced seizure severity and cell death

Effect of age on kainate-induced seizure severity and cell death

Enhanced learning and memory in <italic>GAT1</italic> heterozygous mice

Norepinephrine transporter (NET) is expressed in cardiac sympathetic ganglia of adult rat

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Overexpression of γ-aminobutyric acid transporter subtype I leads to susceptibility to kainic acid-induced seizure in transgenic mice

Cited by 25 publications

References 17 publications

Effect of age on kainate-induced seizure severity and cell death

Effect of age on kainate-induced seizure severity and cell death

Enhanced learning and memory in &lt;italic&gt;GAT1&lt;/italic&gt; heterozygous mice

Norepinephrine transporter (NET) is expressed in cardiac sympathetic ganglia of adult rat

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Enhanced learning and memory in <italic>GAT1</italic> heterozygous mice