Benefits of exercise training in diabetic rats persist after three weeks of detraining

Regarding all benefits of exercise training, a question remains: how long are these benefits kept? This study evaluated the effect of 3-week detraining after 10 weeks of training in STZ-diabetic rats. Male Wistar rats were assigned into: sedentary controls, trained controls, trained–detrained controls, sedentary diabetic, trained diabetic and trained–detrained diabetic. Arterial pressure (AP) and heart rate (HR) were recorded by a data acquisition system. Baroreflex sensitivity (BRS) was evaluated by HR responses to AP changes induced by infusion of vasoactive drugs. Intrinsic heart rate (IHR), sympathetic tonus (ST) and vagal tonus (VT) were evaluated by pharmacological blockade with atenolol and atropine. Spectral analysis of systolic AP and HR variabilities (HRV) was performed to estimate autonomic modulation to the heart and vessels. Diabetes cardiovascular and autonomic dysfunctions were reversed by exercise training and partially maintained in the 3-week detraining period. In controls, training decreased AP and HR and improved BRS, changes that returned to baseline values after detraining. IHR and VT were improved in trained diabetic rats and remained in detrained diabetic ones. LF component of HRV decreased in trained control group. In diabetics, exercise training improved variance, and absolute LF and HF components of HRV. Only HF was maintained in detrained diabetic group. Moreover, there was an inverse relationship between plasma glucose and the absolute HF component of HRV. These changes probably determined the different survival rate of 80% in diabetic detrained and 51% in diabetic sedentary rats.     

Uptake of postprandial lipoproteins into bone in vivo: impact on osteoblast function

Dietary lipids and lipophilic vitamins are transported by postprandial lipoproteins and are required for bone metabolism. Despite that, it remains unknown whether bone cells are involved in the uptake of circulating postprandial lipoproteins in vivo. The current study was performed to investigate a putative participation of bone in the systemic postprandial lipoprotein metabolism in mice, to identify potentially involved cell type populations and to analyze whether lipoprotein uptake affects bone function in vivo. As a model for the postprandial state, chylomicron remnants (CR) were injected intravenously into mice. Next to the liver and compared to other organs, bone appeared to be the second most important organ for the clearance of radiolabeled CR particles from the circulation in vivo. In addition, uptake of radiolabeled CR by primary murine osteoblasts and hepatocytes was quantified to be in a similar range in vitro. A complementary approach with fluorescently labeled CR and immunohistochemical staining for apoE proved that intact CR particles were taken up into bone and liver. Electron microscopy localization studies of bone sections revealed CR uptake into sinusoidal endothelial cells, macrophages and osteoblasts. The relative amount of radiolabeled CR uptake into femoral cortical bone, representing predominantly osteoblasts, and bone marrow, representing predominantly non-osteoblast cells, was within the same range. Most importantly, the injection of vitamin K1-enriched CR resulted in an increase of the degree of osteocalcin carboxylation in vivo while total osteocalcin concentrations remained unaffected, giving functional proof that osteoblasts process CR in vivo. In conclusion, here we demonstrate that bone is involved in the postprandial lipoprotein metabolism in mice. Osteoblasts participate in CR clearance from the circulation, which has a direct impact on the secretory function of osteoblasts.     

Glial and neuronal damage markers in patients with anorexia nervosa

Anorexia nervosa (AN) commonly arises during adolescence leading to interruptions of somatic and psychological development as well as to atrophic brain changes. It remains unclear whether these brain changes are related to the loss of neurons, glia, neuropil or merely due to fluid shifts. We determined leptin levels and two brain-derived damage markers: glial fibrillary acidic protein (GFAP) and neuron-specific enolase (NSE) of 43 acute AN patients and 50 healthy control woman (HCW). Peripheral GFAP and NSE concentrations of AN patients were not elevated and not different from HCW. Subjects with particularly low leptin concentration, indicating severe malnutrition, did not show abnormal values either. During weight recovery the marker proteins remained unchanged. Our preliminary results are in line with neuroimaging studies supporting the reversibility of brain changes in AN and do not substantiate hypotheses relying on the extensive damage of brain cells as an explanation for cerebral atrophy in AN.     

Role of glial cells in the functional expression of LL-37/rat cathelin-related antimicrobial peptide in meningitis

Antimicrobial peptides are intrinsic to the innate immune system in many organ systems, but little is known about their expression in the central nervous system. We examined cerebrospinal fluid (CSF) and serum from patients with active bacterial meningitis to assess antimicrobial peptides and possible bactericidal properties of the CSF. We found antimicrobial peptides (human cathelicidin LL-37) in the CSF of patients with bacterial meningitis but not in control CSF. We next characterized the expression, secretion, and bactericidal properties of rat cathelin-related antimicrobial peptide, the homologue of the human LL-37, in rat astrocytes and microglia after incubation with different bacterial components. Using real-time polymerase chain reaction and Western blotting, we determined that supernatants from both astrocytes and microglia incubated with bacterial component supernatants had antimicrobial activity. The expression of rat cathelin-related antimicrobial peptide in rat glial cells involved different signal transduction pathways and was induced by the inflammatory cytokines interleukin 1beta and tumor necrosis factor. In an experimental model of meningitis, infant rats were intracisternally infected with Streptococcus pneumoniae, and rat cathelin-related antimicrobial peptide was localized in glia, choroid plexus, and ependymal cells by immunohistochemistry. Together, these results suggest that cathelicidins produced by glia and other cells play an important part in the innate immune response against pathogens in central nervous system bacterial infections.     

Effects of acute and chronic apomorphine on sex behavior and copulation-induced neural activation in the male rat

Apomorphine is a non-selective dopaminergic receptor agonist. Because of its pro-erectile effects, apomorphine is clinically used for treatment of erectile dysfunction. We investigated the effects of subcutaneous apomorphine administration (0.4 mg/kg rat) on sexual behavior and mating-induced Fos-expression following acute (day 1) or chronic apomorphine treatment (days 8 and 15) in sexually experienced male rats. Consistent facilitatory effects of apomorphine were observed in the reduced numbers of mounts and intromissions over time and an increased ejaculation frequency on day 1. The first post-ejaculatory interval, however, was lengthened, while other behavioral parameters were unaffected. Fos-immunoreactivity induced by acute apomorphine administration (barrel cortex, paraventricular hypothalamic nucleus, central amygdala and locus coeruleus) was strongly reduced after chronic administration. After mating, induction of Fos-immunoreactivity was observed in well-known areas like medial preoptic nucleus and the posterodorsal medial amygdaloid area. Apomorphine, however, reduced mating-induced Fos-immunoreactivity in the nucleus accumbens shell and prevented its occurrence in its core area. This remarkable apomorphine effect was not observed in any other brain area. We conclude that the behavioral (pro-erectile) effects of apomorphine are consistent over time, and that the diminished accumbens-Fos-immunoreactivity and the elongated post-ejaculatory interval may reflect a decreased response to remote cues from the estrus female.     

Leptin and its associations with measures of psychopathology in patients with anorexia nervosa

Apart from energy homeostasis leptin has been shown to be involved in a number of neuronal networks. The aim of this study was to investigate how the residual variance of leptin levels, after controlling for BMI, is linked to eating-disorder-specific psychopathology and sexual desire in patients with anorexia nervosa (AN) compared to healthy controls. The sample included 57 subjects with acute AN and 77 healthy controls. Psychopathology was determined by EDI-2 and SCL-90-R and sexual problems were rated according to the Structured Interview of Anorexia Nervosa and Bulimic Syndromes (SIAB-EX). Plasma leptin was assessed by ELISA. Patients with a high drive for thinness had lower leptin levels at a given BMI and low leptin levels were associated with sexual problems, i.e. the absence of sexual desire and intimate relationships. Our results are in accordance with recent animal experiments linking low leptin levels with decreased sexual interest irrespective of body weight.