It is well established that the mammalian circadian system consists of pacemaker cells in the suprachiasmatic nuclei (SCN). The mouse has become increasingly important in understanding the circadian timing system, due to the availability of mutant animals with abnormal circadian rhythms. In the present paper, we describe the organization of the mouse SCN, comparing the wild type and Clock mutant animal, with a special focus on those peptides bearing an upstream E-box element (vasopressin, vasoactive intestinal peptide, cholecystokinin and substance P). To this end, we describe the distribution of the foregoing SCN peptidergic cell types as well as gastrin-related peptide, calretinin, calbindin, somatostatin, neurotensin and retinal input to the SCN (determined by both tract tracing and fos-immunoreactivity in response to a light pulse). The Clock mutant mouse has decreased expression of vasopressin mRNA and protein in the SCN, with normal patterns of expression elsewhere in the brain. No other differences were detected between the Clock mutant and the wild type mouse. The results are consistent with the hypothesis that there are multiple regulatory elements of clock-controlled genes in the SCN.
The differences observed pertain to genes related to intracellular calcium homeostasis and genes involved in the control of mitochondrial oxidative phosphorylation and protein turnover, both at the level of protein synthesis and proteolysis. Assessment of these differences may be a useful tool for the design of novel therapeutic strategies to fight this devastating syndrome.
Background: Duchenne muscular dystrophy results from mutation of the dystrophin gene, causing skeletal and cardiac muscle loss of function. The mdx mouse model of Duchenne muscular dystrophy is widely utilized to evaluate the potential of therapeutic regimens to modulate the loss of skeletal muscle function associated with dystrophin mutation. Importantly, progressive loss of diaphragm function is the most consistent striated muscle effect observed in the mdx mouse model, which is the same as in patients suffering from Duchenne muscular dystrophy.
Circadian rhythmicity in mammals, is controlled by the suprachiasmatic nuclei (SCN) of the hypothalamus. We previously described a discrete subnucleus in the core of the hamster SCN containing calbindin-D28k-positive cells which are fos-positive in response to a light pulse. Ablation of this subnucleus results in loss of circadian locomotor rhythmicity even when other parts of the SCN are spared. Here we show that Tau mutant hamsters have significantly more calbindin-D28k in the SCN than do wild type hamsters, and that SCN calbindin-immunoreactivity in the SCN increases in the dark. This is correlated with changes in magnitude of light mediated phase shifts in locomotion. The data are consistent with a role for calbindin cells in light mediated entrainment and phase shifting.
The hypothesis we tested was that administering corticotropin-releasing factor receptor agonists preserves muscle mass during cancer that is related to changes in tissue gene expression. cDNA microarrays were used to compare mRNAs from muscle and adipose tissues of non-treated and agonist-treated tumor-bearing rats. In muscle of non-tumor-bearing agonist-treated animals we observed decreased expression of genes associated with fatty acid uptake and esterification. In tumor-bearing animals, CRF2R agonist administration produced decreased mRNA content of the atrogene lipin-1. In white adipose tissue, agonist treatment of non-tumor-bearing animals induced genes typically related to muscle structure and function. The fact that this treatment decreased expression of atrogenes could have clinical application. In addition, agonist treatment changed the gene pattern of adipose tissue to render it similar to that of skeletal muscle; thus, treatment with this agonist alters the gene pattern to what could be called "muscularization of white adipose tissue."
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