Adeno-associated viral glutamate decarboxylase expression in the lateral nucleus of the rat hypothalamus reduces feeding behavior

In vivo gene transfer of glutamate decarboxylase (GAD) has been explored as a means of inducing or increasing the production of the inhibitory amino-acid neurotransmitter, GABA. This strategy has been applied to neuroprotection, seizure prevention, and neuromodulation. In the present experiment, AAV...

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Bibliographic Details
Published in:Gene therapy Vol. 11; no. 9; pp. 797 - 804
Main Authors: Noordmans, A J, Song, D K, Noordmans, C J, Garrity-Moses, M, During, M J, Fitzsimons, H L, Imperiale, M J, Boulis, N M
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 01.05.2004
Nature Publishing Group
Subjects:
Adeno-associated virus
Adenoviridae - genetics
Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy
Animals
Applied cell therapy and gene therapy
Biological and medical sciences
Biomedical and Life Sciences
Biomedicine
Biotechnology
Body weight gain
Cell Biology
Eating - genetics
Feeding behavior
Feeding Behavior - physiology
Food consumption
Fundamental and applied biological sciences. Psychology
gamma-Aminobutyric Acid - biosynthesis
Gene Expression
Gene Targeting - methods
Gene Therapy
Gene transfer
Gene Transfer Techniques
Glutamate decarboxylase
Glutamate Decarboxylase - genetics
Glutamate Decarboxylase - metabolism
Health. Pharmaceutical industry
Human Genetics
Hybridization
Hypothalamic Area, Lateral - enzymology
Hypothalamic Area, Lateral - physiology
Hypothalamus
Hypothalamus (lateral)
Industrial applications and implications. Economical aspects
Medical sciences
Microinjection
Microinjections - methods
Nanotechnology
Neuromodulation
Neuroprotection
Post-transcription
Rats
Rats, Wistar
Regulatory sequences
research-article
Seizures
Stereotaxic Techniques
Transfusions. Complications. Transfusion reactions. Cell and gene therapy
Weight Gain - genetics
Weight Gain - physiology
γ-Aminobutyric acid
GABA
adeno-associated virus
hypothalamus
glutamate decarboxylase
feeding
Feeding behavior
Rat
Enzyme
Lateral nucleus
Rodentia
Lyases
Glutamate decarboxylase
Hypothalamus
Dependovirus
Virus
Carbon-carbon lyases
Vertebrata
Mammalia
Parvoviridae
Carboxy-lyases
Gene therapy
Vector
Parvovirinae
ISSN:0969-7128, 1476-5462
Online Access:Get full text
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Summary:In vivo gene transfer of glutamate decarboxylase (GAD) has been explored as a means of inducing or increasing the production of the inhibitory amino-acid neurotransmitter, GABA. This strategy has been applied to neuroprotection, seizure prevention, and neuromodulation. In the present experiment, AAV2 was used to transfer the genes for green fluorescence protein (GFP) and GAD65 into the lateral nucleus of the rat hypothalamus. Microinjection of 500 nl of AAV2 resulted in transduction of a 0.25±0.04 mm 3 with targeting errors of X=0.48 mm, Y=0.18 mm, Z=0.37 mm using standard stereotactic technique. Pre- and postinjection food and water consumption, urine and feces production, and weight were recorded. In comparison with rAAVCAGGFP- and PBS-injected animals, rats treated with rAAVCAGGAD65 demonstrated reduced weight gain (P<0.014) and transiently reduced daily food consumption (P<0.007) during the postoperative period. No changes in water consumption or waste production were recorded. Effective GAD65 gene transfer was confirmed with in situ hybridization using a probe to the woodchuck post-transcriptional regulatory element sequence included in the vector. These findings suggest that increased GABA production in lateral nucleus of the hypothalamus induced by GAD65 gene transfer may reduce weight gain through reduced feeding.
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ISSN:0969-7128
1476-5462
DOI:10.1038/sj.gt.3302223