title: Hypothalamic plasticity of neuropeptide Y is lacking in brain-type creatine kinase double knockout mice with defective thermoregulation.
abstract: The neural substrate of adaptive thermoregulation in mice lacking both brain-type creatine kinase isoforms is further investigated. The cytosolic brain-type creatine kinase (CK-B) and mitochondrial ubiquitous creatine kinase (UbCKmit) are expressed in neural cells throughout the central and peripheral nervous system, where they have an important role in cellular energy homeostasis. Several integral functions appear altered when creatine kinases are absent in the brain (Jost et al., 2002; Streijger et al., 2004, 2005), which has been explained by inefficient neuronal transmission. The CK--/-- double knockout mice demonstrate every morning a body temperature drop of ~1.0 °C, and they have impaired thermogenesis, as revealed by severe hypothermia upon cold exposure. This defective thermoregulation is not associated with abnormal food intake, decreased locomotive activity, or increased torpor sensitivity. Although white and brown adipose tissue fat pads are diminished in CK--/-- mice, intravenous norepinephrine infusion results in a normal brown adipose tissue response with increasing core body temperatures, indicating that the sympathetic innervation functions correctly (Streijger et al., 2009). This study revealed c-fos changes following a cold challenge, and that neuropeptide Y levels were decreased in the paraventricular nucleus of wildtype, but not CK--/--, mice. A reduction in hypothalamic neuropeptide Y is coupled to increased uncoupling protein 1 expression in brown adipose tissue, resulting in thermogenesis. In CK--/-- mice the neuropeptide Y levels did not change. This lack of hypothalamic plasticity of neuropeptide Y might be the result of inefficient neuronal transmission or can be explained by the previous observation of reduced circulating levels of leptin in CK--/-- mice.
authors.affiliation: Department of Cell Biology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. Electronic address: i.vanderzee@ncmls.ru.nl.
authors.forename: Catharina E E M
authors.initials: CEEM
authors.lastname: Van der Zee
mesh_terms: D000818:Animals; D001831:Body Temperature / Q000235:genetics; D001833:Body Temperature Regulation / Q000235:genetics*; D002467:Cell Nucleus / Q000378:metabolism; D003080:Cold Temperature; D052276:Creatine Kinase, BB Form / Q000172:deficiency* / Q000235:genetics; D052281:Creatine Kinase, Mitochondrial Form / Q000172:deficiency* / Q000235:genetics; D055786:Gene Knockout Techniques; D007031:Hypothalamus / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D009473:Neuronal Plasticity / Q000235:genetics*; D009478:Neuropeptide Y / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism
chemical_list: D009478:Neuropeptide Y; D016760:Proto-Oncogene Proteins c-fos; D052276:Creatine Kinase, BB Form; D052281:Creatine Kinase, Mitochondrial Form
keywords: Brain-type creatine kinase; Brown adipose tissue thermogenesis; C-fos immunoreactivity; Leptin; Mitochondrial ubiquitous creatine kinase; Neuropeptide Y immunoreactivity; Paraventricular nucleus