| LDR | | 00000nam u2200205 4500 |
| 001 | | 000000436426 |
| 005 | | 20200228143608 |
| 008 | | 200131s2019 ||||||||||||||||| ||eng d |
| 020 | |
▼a 9781085593038 |
| 035 | |
▼a (MiAaPQ)AAI13808933 |
| 040 | |
▼a MiAaPQ
▼c MiAaPQ
▼d 247004 |
| 082 | 0 |
▼a 614 |
| 100 | 1 |
▼a Farina, Maxwell G. |
| 245 | 10 |
▼a Localized Hippocampal Glutamine Synthetase Knockout: a Novel Model of Mesial Temporal Lobe Epilepsy. |
| 260 | |
▼a [S.l.]:
▼b Yale University.,
▼c 2019. |
| 260 | 1 |
▼a Ann Arbor:
▼b ProQuest Dissertations & Theses,
▼c 2019. |
| 300 | |
▼a 49 p. |
| 500 | |
▼a Source: Dissertations Abstracts International, Volume: 81-02, Section: B. |
| 500 | |
▼a Advisor: Eid, Tore |
| 502 | 1 |
▼a Thesis (M.D.)--Yale University, 2019. |
| 506 | |
▼a This item must not be sold to any third party vendors. |
| 506 | |
▼a This item must not be added to any third party search indexes. |
| 520 | |
▼a The purpose of this study was to create and optimize a model of mesial temporal lobe epilepsy through selective depletion of glutamine synthetase (GS) in the mouse hippocampus. Following validation of the model, preliminary studies attempted to characterize morphological astrocytic and synaptic changes that result from GS deficiency. Aim 1 established a novel mouse model of GS knockout in hippocampal astrocytes. Aim 2 tested whether localized hippocampal knockout of GS causes mice to exhibit an epilepsy-like phenotype. Aim 3 characterized the cellular effects of localized GS loss. To generate the knockout, Glul-floxed C57BL/6J mice were injected with four different adeno-associated viral vectors containing Cre-recombinase expression cassettes. Mice were also implanted with intracranial depth or screw recording electrodes and monitored for spontaneous seizures using 24-hour video-EEG recording for two weeks. To assess for provoked seizure sensitivity, seizures were induced with pentylenetetrazol (PTZ) prior to perfusion fixation. Brains were perfused, sectioned, and immunostained for analysis using standard and STED fluorescence microscopy. Knockout of GS, as evidenced by loss of GS immunoreactivity, was found over a greater area in brain regions injected with the AAV5 CMV and AAV8 GFAP serotypes. In addition, within each GS knockout region, AAV8 GFAP exhibited a significantly greater efficiency of knockdown compared to AAV5 CMV Legacy and AAV8 CMV (83.1% decreased fluorescence intensity, p=0.0003) and compared to AAV5 CMV (20.2% decreased fluorescence intensity, p=0.018). AAV8 GFAP exhibited near perfect target specificity (98.7% of GFP+ cells were astrocytes), while AAV5 CMV Legacy, AAV5 CMV, and AAV8 CMV targeted mostly neurons with varied degrees astrocyte labeling detected (10.0%, 21.3%, and 12.7% astrocytes, respectively. Sixty percent (3/5) of mice injected with AAV8 GFAP exhibited an epilepsy-like phenotype including spontaneous recurrent seizures that were clustered in the morning hours. Twenty-five percent (1/4) of control mice seized spontaneously over the same period. Additionally, focal GS knockout mice demonstrated significantly lower time to initial clonic twitch following PTZ administration compared to control mice (mean 짹 SEM: 41.2 짹 3.2 seconds vs. 65.83 짹 12.9 seconds, respectively |
| 590 | |
▼a School code: 0265. |
| 650 | 4 |
▼a Neurosciences. |
| 650 | 4 |
▼a Medicine. |
| 650 | 4 |
▼a Molecular biology. |
| 650 | 4 |
▼a Physiology. |
| 650 | 4 |
▼a Epidemiology. |
| 650 | 4 |
▼a Public health. |
| 650 | 4 |
▼a Health sciences. |
| 690 | |
▼a 0317 |
| 690 | |
▼a 0564 |
| 690 | |
▼a 0307 |
| 690 | |
▼a 0573 |
| 690 | |
▼a 0566 |
| 690 | |
▼a 0766 |
| 690 | |
▼a 0719 |
| 710 | 20 |
▼a Yale University.
▼b Yale School of Medicine. |
| 773 | 0 |
▼t Dissertations Abstracts International
▼g 81-02B. |
| 773 | |
▼t Dissertation Abstract International |
| 790 | |
▼a 0265 |
| 791 | |
▼a M.D. |
| 792 | |
▼a 2019 |
| 793 | |
▼a English |
| 856 | 40 |
▼u http://www.riss.kr/pdu/ddodLink.do?id=T15490558
▼n KERIS
▼z 이 자료의 원문은 한국교육학술정보원에서 제공합니다. |
| 980 | |
▼a 202002
▼f 2020 |
| 990 | |
▼a ***1008102 |
| 991 | |
▼a E-BOOK |