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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Vydáno v:	Gene therapy Ročník 11; číslo 9; s. 797 - 804
Hlavní autoři:	Noordmans, A J, Song, D K, Noordmans, C J, Garrity-Moses, M, During, M J, Fitzsimons, H L, Imperiale, M J, Boulis, N M
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	London Nature Publishing Group UK 01.05.2004 Nature Publishing Group
Témata:	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
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Shrnutí:	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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 ObjectType-Article-2 ObjectType-Feature-1 content type line 23
ISSN:	0969-7128 1476-5462
DOI:	10.1038/sj.gt.3302223