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Cerebellum. 2018 Apr;17(2):152-164. doi: 10.1007/s12311-017-0880-7.

NCB5OR Deficiency in the Cerebellum and Midbrain Leads to Dehydration and Alterations in Thirst Response, Fasted Feeding Behavior, and Voluntary Exercise in Mice.

Stroh MA1,2,3,4, Winter MK5, McCarson KE5,6, Thyfault JP7,8, Zhu H9,10,11.

Author information

1
Landon Center on Aging, University of Kansas Medical Center, Kansas City, KS, 66160, USA.
2
Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS, 66160, USA.
3
Neuroscience Graduate Program, University of Kansas Medical Center, Kansas City, KS, 66160, USA.
4
Department of Neurology, Washington University in St. Louis School of Medicine, St. Louis, MO, 63110, USA.
5
Kansas Intellectual and Developmental Disabilities Research Center, University of Kansas Medical Center, Kansas City, KS, 66160, USA.
6
Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS, 66160, USA.
7
Department of Molecular Integrative Physiology, University of Kansas Medical Center, Kansas City, KS, 66160, USA.
8
Research Service, Kansas City VA Medical Center, Kansas City, MO, 64128, USA.
9
Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS, 66160, USA. hzhu@kumc.edu.
10
Neuroscience Graduate Program, University of Kansas Medical Center, Kansas City, KS, 66160, USA. hzhu@kumc.edu.
11
Department of Clinical Laboratory Sciences, University of Kansas Medical Center, 3901 Rainbow Blvd., MSN 4048G-Eaton, Kansas City, KS, 66160, USA. hzhu@kumc.edu.

Abstract

Cytosolic NADH-cytochrome-b5-oxidoreductase (NCB5OR) is ubiquitously expressed in animal tissues. We have previously reported that global ablation of NCB5OR in mice results in early-onset lean diabetes with decreased serum leptin levels and increased metabolic and feeding activities. The conditional deletion of NCB5OR in the mouse cerebellum and midbrain (conditional knock out, CKO mice) results in local iron dyshomeostasis and altered locomotor activity. It has been established that lesion to or removal of the cerebellum leads to changes in nutrient organization, visceral response, feeding behavior, and body weight. This study assessed whether loss of NCB5OR in the cerebellum and midbrain altered feeding or metabolic activity and had an effect on serum T3, cortisol, prolactin, and leptin levels. Metabolic cage data revealed that 16 week old male CKO mice had elevated respiratory quotients and decreased respiratory water expulsion, decreased voluntary exercise, and altered feeding and drinking behavior compared to wild-type littermate controls. Most notably, male CKO mice displayed higher consumption of food during refeeding after a 48-h fast. Echo MRI revealed normal body composition but decreased total water content and hydration ratios in CKO mice. Increased serum osmolality measurements confirmed the dehydration status of male CKO mice. Serum leptin levels were significantly elevated in male CKO mice while prolactin, T3, and cortisol levels remain unchanged relative to wild-type controls, consistent with elevated transcript levels for leptin receptors (short form) in the male CKO mouse cerebellum. Taken together, these findings suggest altered feeding response post starvation as a result of NCB5OR deficiency in the cerebellum.

KEYWORDS:

Cerebellum; Dehydration; Exercise; Leptin; Mouse; Ncb5or; RER

PMID:
28887630
DOI:
10.1007/s12311-017-0880-7

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