Development of epilepsy after spatially restricted viral-vector-mediated silencing of parvalbumin-expressing GABAergic interneurons in the mouse

2014 ◽  
Vol 2 (Suppl. 1) ◽  
pp. A1.43
Author(s):  
Meinrad Drexel
Keyword(s):  
Viral Vector ◽  
Gabaergic Interneurons

074 Basal Forebrain GABAergic Neurons Promote Arousal by Disinhibiting the Orexin Neurons via Local GABAergic Interneurons

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A31-A31
Author(s):  
Michela Cristofolini ◽  
Roberto De Luca ◽  
Anne Venner ◽  
Loris Ferrari ◽  
Kevin Grace ◽  
...  
Keyword(s):  
Basal Forebrain ◽  
Viral Vector ◽  
Brain Slices ◽  
Nrem Sleep ◽  
Gabaergic Neurons ◽  
Gabaergic Interneurons ◽  
Optogenetic Stimulation ◽  
Stimulation Of

Abstract Introduction Optogenetic and chemogenetic studies have shown that activation of basal forebrain (BF) GABAergic neurons rapidly wakes up mice from non-REM (NREM) sleep. These wake-promoting responses have been attributed to BF GABAergic neurons projecting to the cerebral cortex and more specifically to the inhibition of cortical fast-spiking interneurons. Tracing studies have however found that BF GABAergic neurons also densely innervate the lateral hypothalamus (LH) perifornical area, although the role of this pathway in behavioral state control remains mostly unexplored. Methods We conducted in vivo and in vitro optogenetic studies. We selectively expressed channelrhodopsin-2 (ChR2) in BF GABAergic neurons by injecting a cre-dependent viral vector encoding for ChR2 into the BF of VGAT-cre mice. We photostimulated the BF GABAergic input to the LH with optical fibers placed into the LH of EEG instrumented mice. For in vitro recordings we expressed ChR2 in BF GABAergic neurons and we fluorescently labeled orexin or LH GABAergic neurons. We recorded in brain slices from identified orexin neurons or GABA neurons while photostimulating the BF GABAergic input. Results Optogenetic stimulation of the BF GABAergic fibers in the LH produced rapid arousals from NREM sleep. The same stimulation however did not wake up the mice if they were in REM sleep. We conducted additional studies in brain slices to identify the postsynaptic neurons in the LH targeted by the BF GABAergic input. We found that while optogenetic stimulation of the BF GABAergic input did not produce opto-evoked synaptic responses in the orexin neurons, it produced short-latency opto-evoked inhibitory postsynaptic currents (IPSCs) in LH GABAergic neurons. These opto-evoked IPSCs were GABAA receptor-mediated and were maintained in tetrodotoxin (TTX) indicating monosynaptic connectivity. We have previously found that orexin neurons are inhibited by local LH GABAergic neurons. Our hypothesis is that these local GABAergic interneurons are the target of the BF GABAergic arousal input. Conclusion BF GABAergic neurons drive arousal through projections to the LH. We propose that this arousal response is due to the inhibition of local GABAergic interneurons which in turn disinhibit the LH wake-promoting neurons including the orexin neurons. Support (if any) NS091126 and HL149630

1440: Novel Non-Viral Vector Using Biodegradable Thermo-Sensitive Polymer (Regel®) in the Gene Therpy of Erectile Dysfunction

2004 ◽  
Vol 171 (4S) ◽  
pp. 379-379 ◽  
Author(s):  
Ji-Kan Ryu ◽  
Hwa-Yeon Shin ◽  
Minhyung Lee ◽  
Sun U. Song ◽  
Ki-Hak Moon ◽  
...  
Keyword(s):  
Erectile Dysfunction ◽  
Viral Vector

Viral Vector

2020 ◽  
Author(s):  
Keyword(s):  
Viral Vector

Enhanced Stability and Controlled Delivery of MOF Encapsulated Vaccines and Their Immunogenic Response In Vivo

2018 ◽  
Author(s):  
Michael Luzuriaga ◽  
Raymond P. Welch ◽  
Madushani Dharmawardana ◽  
Candace Benjamin ◽  
Shaobo Li ◽  
...  
Keyword(s):  
Viral Vector ◽  
Controlled Delivery ◽  
Conformational Structure ◽  
Spectroscopy Analysis ◽  
Zeolitic Imidazolate Framework ◽  
Structural Conformation ◽  
Depth Study ◽  
Viral Nanoparticle

<div><div><div><p>Vaccines have an innate tendency to lose their structural conformation upon environmental and chemical stressors. A loss in conformation reduces the therapeutic ability to prevent the spread of a pathogen. Herein, we report an in-depth study of zeolitic imidazolate framework-8 (ZIF-8) and its ability to provide protection for a model viral vector against dena- turing conditions. The immunoassay and spectroscopy analysis together demonstrate enhanced thermal and chemical stability to the conformational structure of the encapsulated viral nanoparticle. The long-term biological activity of this virus-ZIF composite was investigated in animal models to further elucidate the integrity of the encapsulated virus, the bio-safety, and immunogenicity of the overall composite. Additionally, histological analysis found no observable tissue damage in the skin or vital organs in mice, following multiple subcutaneous administrations. This study shows that ZIF-based protein composites are strong candidates for improved preservation of proteinaceous drugs, are biocompatible, and capable of controlling the release and adsorption of drugs in vivo.</p></div></div></div>

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