American journal of physiology. Regulatory, integrative and comparative physiology
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Am. J. Physiol. Regul. Integr. Comp. Physiol. · May 2008
Sleep deprivation can inhibit adult hippocampal neurogenesis independent of adrenal stress hormones.
Sleep deprivation (SD) can suppress cell proliferation in the hippocampal dentate gyrus of adult male rodents, suggesting that sleep may contribute to hippocampal functions by promoting neurogenesis. However, suppression of cell proliferation in rats by the platform-over-water SD method has been attributed to elevated corticosterone (Cort), a potent inhibitor of cell proliferation and nonspecific correlate of this procedure. We report here results that do not support this conclusion. ⋯ In these latter rats, Cort intake via water was reduced by 60% during SD; upregulation of cell proliferation by reduced Cort intake may obscure inhibitory effects of sleep loss on cell proliferation. SD had no effect on the percentage of new cells expressing a neuronal phenotype. These results demonstrate that the Cort replacement method is critical for detecting an effect of SD on cell proliferation and support a significant role for sleep in adult neurogenesis.
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Am. J. Physiol. Regul. Integr. Comp. Physiol. · May 2008
Osmoregulatory fluid intake but not hypovolemic thirst is intact in mice lacking angiotensin.
Water intakes in response to hypertonic, hypovolemic, and dehydrational stimuli were investigated in mice lacking angiotensin II as a result of deletion of the angiotensinogen gene (Agt-/- mice), and in C57BL6 wild-type (WT) mice. Baseline daily water intake in Agt-/- mice was approximately threefold that of WT mice because of a renal developmental disorder of the urinary concentrating mechanisms in Agt-/- mice. Intraperitoneal injection of hypertonic saline (0.4 and 0.8 mol/l NaCl) caused a similar dose-dependent increase in water intake in both Agt-/- and WT mice during the hour following injection. ⋯ Polyethylene glycol treatment increased Fos-immunoreactivity in the subfornical organ, OVLT, and supraoptic nuclei in WT mice but only increased Fos-immunoreactivity in the supraoptic nucleus in Agt-/- mice. These data show that brain angiotensin is not essential for the adequate functioning of neural pathways mediating osmoregulatory thirst. However, angiotensin II of either peripheral or central origin is probably necessary for thirst and salt appetite that results from hypovolemia.
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Am. J. Physiol. Regul. Integr. Comp. Physiol. · May 2008
Impaired lymphatic cerebrospinal fluid absorption in a rat model of kaolin-induced communicating hydrocephalus.
It has been assumed that the pathogenesis of hydrocephalus includes a cerebrospinal fluid (CSF) absorption deficit. Because a significant portion of CSF absorption occurs into extracranial lymphatics located in the olfactory turbinates, the purpose of this study was to determine whether CSF transport was compromised at this location in a kaolin-induced communicating (extraventricular) hydrocephalus model in rats. Under 1-3% halothane anesthesia, kaolin (n = 10) or saline (n = 9) was introduced into the basal cisterns of Sprague-Dawley rats, and the development of hydrocephalus was assessed 1 wk later using MRI. ⋯ The CSF tracer enrichment in the olfactory turbinates (expressed as percent injected/g tissue) in the kaolin rats averaged 0.99 +/- 0.39 and was significantly lower than that measured in the saline controls (5.86 +/- 0.32; P < 0.00001). The largest degree of ventriculomegaly was associated with the lowest levels of lymphatic CSF uptake with lateral ventricular expansion occurring only when almost all of the lymphatic CSF transport capacity had been compromised. We conclude that lymphatic CSF absorption is impaired in a kaolin-communicating hydrocephalus model and that the degree of this impediment may contribute to the severity of the induced disease.
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Am. J. Physiol. Regul. Integr. Comp. Physiol. · Apr 2008
Comparative StudyEnhanced muscle fatigue occurs in male but not female ASIC3-/- mice.
Muscle fatigue is associated with a number of clinical diseases, including chronic pain conditions. Decreases in extracellular pH activates acid-sensing ion channel 3 (ASIC3), depolarizes muscle, protects against fatigue, and produces pain. We examined whether ASIC3-/- mice were more fatigable than ASIC3+/+ mice in a task-dependent manner. ⋯ Muscle fiber types, measured by counting ATPase-stained whole muscle sections, were similar in calf muscles from male and female ASIC3+/+ mice. These data suggest that both ASIC3 and testosterone are necessary to protect against muscle fatigue in a task-dependent manner. Also, differences in expression of ASIC3 and the development of exercise-induced fatigue could explain the female predominance in clinical syndromes of pain that include muscle fatigue.
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Am. J. Physiol. Regul. Integr. Comp. Physiol. · Apr 2008
Regulation of Fto/Ftm gene expression in mice and humans.
Two recent, large whole-genome association studies (GWAS) in European populations have associated a approximately 47-kb region that contains part of the FTO gene with high body mass index (BMI). The functions of FTO and adjacent FTM in human biology are not clear. We examined expression of these genes in organs of mice segregating for monogenic obesity mutations, exposed to underfeeding/overfeeding, and to 4 degrees C. ⋯ One of these nominal CUTL1 sites includes rs8050136, a SNP associated with high body mass. The A allele of rs8050136 preferentially bound CUTL1[corrected] in human fibroblast DNA. 70% knockdown of CUTL1 expression in human fibroblasts decreased FTO and FTM expression by 90 and 65%, respectively. Animals and humans with various genetic interruptions of FTO or FTM have phenotypes reminiscent of aspects of the Bardet-Biedl obesity syndrome, a confirmed "ciliopathy." FTM has recently been shown to be a ciliary basal body protein.