| Title |
Epigenetic Suppression of GADs Expression is Involved in Temporal Lobe Epilepsy and Pilocarpine-Induced Mice Epilepsy
|
|---|---|
| Published in |
Neurochemical Research, May 2016
|
| DOI | 10.1007/s11064-016-1891-3 |
| Pubmed ID | |
| Authors |
Jin-Gang Wang, Qing Cai, Jun Zheng, Yu-Shu Dong, Jin-Jiang Li, Jing-Chen Li, Guang-Zhi Hao, Chao Wang, Ju-Lei Wang |
| Abstract |
Recent studies have shown that histone acetylation is involved with the regulation of enzyme glutamate decarboxylases (GADs), including GAD67 and GAD65. Here, we investigated the histone acetylation modifications of GADs in the pathogenesis of epilepsy and explored the therapeutic effect of a novel second-generation histone deacetylase inhibitor (HDACi) JNJ-26481585 in epilepsy animals. We revealed the suppression of GADs protein and mRNA level, and histone hypoacetylation in patients with temporal lobe epilepsy and pilocarpine-induced epilepsy mice model. Double-immunofluorescence also indicated that the hypoacetyl-H3 was located in hippocampal GAD67/GAD65 positive neurons in epilepsy mice. JNJ-26481585 significantly reversed the decrease of the GAD67/GAD65 both protein and mRNA levels, and the histone hypoacetylation of GABAergic neurons in epilepsy mice. Meanwhile, single-cell real-time PCR performed in GFP-GAD67/GAD65 transgenic mice demonstrated that JNJ-26481585 induced increase of GAD67/GAD65 mRNA level in GABAergic neurons. Furthermore, JNJ-26481585 significantly alleviated the epileptic seizures in mice model. Together, our findings demonstrate inhibition of GADs gene via histone acetylation plays an important role in the pathgenesis of epilepsy, and suggest JNJ-26481585 as a promising therapeutic strategy for epilepsy. |
X Demographics
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| France | 1 | 50% |
| Unknown | 1 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 2 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 33 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 3% |
| Brazil | 1 | 3% |
| Unknown | 31 | 94% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Bachelor | 6 | 18% |
| Researcher | 5 | 15% |
| Student > Master | 4 | 12% |
| Student > Ph. D. Student | 4 | 12% |
| Student > Doctoral Student | 3 | 9% |
| Other | 7 | 21% |
| Unknown | 4 | 12% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 8 | 24% |
| Biochemistry, Genetics and Molecular Biology | 6 | 18% |
| Agricultural and Biological Sciences | 6 | 18% |
| Neuroscience | 5 | 15% |
| Nursing and Health Professions | 2 | 6% |
| Other | 0 | 0% |
| Unknown | 6 | 18% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 26 May 2016.
All research outputs
#18,461,618
of 22,875,477 outputs
Outputs from Neurochemical Research
#1,492
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Outputs of similar age
#251,925
of 335,850 outputs
Outputs of similar age from Neurochemical Research
#28
of 51 outputs
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