Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0153640 (Cerebellum)
 1,777 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
Cerebellum 2018 Apr
PMID:NCB5OR Deficiency in the Cerebellum and Midbrain Leads to Dehydration and Alterations in Thirst Response, Fasted Feeding Behavior, and Voluntary Exercise in Mice. 2888 30

The purpose of this study is to determine the activation of the extrinsic and intrinsic apoptotic pathways in the cerebellum of rats exposed to amygdaloid electrical kindling. Western blot analyses were carried out for caspase-8 and caspase-9, Bid, Bax, and Bcl-2 in the cerebellum and immunohistochemistry of Bid, Bax, cytochrome C, and VDAC (voltage-dependent anion channels) in the cerebellar cortex of Wistar male rats with 0, 15, and 45 kindling stimulations. In the experimental group of 45 stimuli, we observed an increase in protein activation of caspase-9 and truncated Bid and Bax, in addition to a decrease in expression of pro-caspase-8 and the anti-apoptotic protein Bcl-2, determined by Western blot. Moreover, we observed a cytosolic immunopositivity for cytochrome C and a mitochondrial immunolocalization for truncated Bid and Bax in the group of 45 stimuli. In this work, we found an increase of caspase-8, a cysteine-protease that can activate caspase-3 triggering extrinsic apoptosis by signaling of death receptors. However, it also can activate the intrinsic pathway releasing Bid, which performs mitochondrial translocation of Bax, inactivating Bcl-2 and allowing the release of cytochrome C through the opening of the mitochondrial permeability transition pore, promoting the activation of caspase-9 which activates caspase-3, the main executor caspase of apoptosis. Therefore, it is concluded that there is an activation of the intrinsic and extrinsic apoptotic pathways in the cerebellum of rats exposed to the kindling model. Apoptosis signaling pathways can be analyzed as an important developing object of research about the epileptic activity. Graphical Abstract.
Cerebellum 2019 Aug
PMID:Activation of the Extrinsic and Intrinsic Apoptotic Pathways in Cerebellum of Kindled Rats. 3106 84