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Open Journal of Neuroscience

ISSN: 2075-9088
Volume 5, 2017


Open Journal of Neuroscience, 2017, 5-1 [Research Article]

Impaired Striatal GABA Outflow in Leptin Receptor Deficient Rats - The Role of Glucose and KATP Channels

Sonya Carvalho Neto1,0,*, Philipp Capetian2,0, Anett Schumacher3, Andreas Moser1,4

1 Center of Brain, Behavior and Metabolism, Neurochemical Research Group, Department of Neurology, University of Luebeck, Germany.
2 Department of Neurology, University of Wuerzburg, Germany.
3 Department of Psychology (Scarborough), University of Toronto, Canada.
4 Freiburg Institute for Advanced Studies, University of Freiburg, Germany.
0 both authors contributed equally

Corresponding Author & Address:

Sonya Carvalho Neto*
Center of Brain, Behavior and Metabolism, Neurochemical Research Group, Department of Neurology, University of Luebeck, Germany; Phone: +49 451 50043421; Email: sonya.neto@neuro.uni-luebeck.de

Article History:
Published: 21st August, 2017   Accepted: 21st August, 2017
Received: 4th April, 2017      

© Neto et al; licensee Ross Science Publishers

ROSS Open Access articles will be distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided that the original work will always be cited properly.

Keywords: ATP-sensitive-potassium-channels, Leptin, GABA, caudate nucleus, obesity, diabetes mellitus, Zucker diabetic fatty rat.

Abstract:

The leptin receptor (LepR) is considered to be crucial for feedback mechanisms of food intake, body weight and glucose homeostasis. Its activity has been linked to ATP-dependent potassium (KATP) channels that couple bioenergetic metabolism to membrane excitability. In previous studies, it has been demonstrated that glucose modulates striatal γ-aminobutyric acid (GABA) outflow through KATP channels in slice preparations of the rat caudate nucleus. Our goal was to assess the impact of the LepR mutation on this mechanism. Slices of the caudate nucleus from heterozygous (Fa/fa) and homozygous (fa/fa) Zucker diabetic fatty rats (ZDF) and control Wistar rats were incubated with two different doses of glucose. GABA outflow was measured by means of high performance liquid chromatography (HPLC) with electrochemical detection. Glucose reduction (from 10 to 7 mM) resulted in a decreased GABA outflow in Wistar rats. In contrast, GABA outflow of striatal slices of LepR Fa/fa and LepR fa/fa rats remained nearly unchanged when extracellular glucose levels were lowered. The KATP channel blocker glibenclamide (Glb, 10 µM) prevented GABA outflow reduction in control rats at glucose concentrations of 7 mM, implying the involvement of KATP-channels. However, no change of GABA outflow was observed in LepR mutant rats after Glb addition. Although heterozygous ZDF rats possess one healthy LepR allele, no difference could be observed between lean heterozygous and obese homozygous animals. In summary, we demonstrate for the first time an impaired striatal GABA outflow in response to changing glucose levels in heterozygous and homozygous LepR mutant rats.



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