Emergence and Progression of Behavioral Motor Deficits and Skeletal Muscle Atrophy across the Adult Lifespan of the Rat.

The facultative loss of muscle mass and function during aging (sarcopenia) poses a serious threat to our independence and health. When activities of daily living are impaired (clinical phase), it appears that the processes leading to sarcopenia have been ongoing in humans for decades (preclinical phase). Here, we examined the natural history of sarcopenia in male outbred rats to compare the occurrence of motor behavioral deficits with the degree of muscle wasting and to explore the muscle-associated processes of the preclinical and clinical phases, respectively. Selected metrics were validated in female rats. We used the soleus muscle because of its long duty cycles and its importance in postural control. Results show that gait and coordination remain intact through middle age (40-60% of median lifespan) when muscle mass is largely preserved relative to body weight. However, the muscle shows numerous signs of remodeling with a shift in myofiber-type composition toward type I. As fiber-type prevalence shifted, fiber-type clustering also increased. The number of hybrid fibers, myofibers with central nuclei, and fibers expressing embryonic myosin increased from being barely detectable to a significant number (5-10%) at late middle age. In parallel, TGFß1, Smad3, FBXO32, and MuRF1 mRNAs increased. In early (25-month-old) and advanced (30-month-old) aging, gait and coordination deteriorate with the progressive loss of muscle mass. In late middle age and early aging due to type II atrophy (>50%) followed by type I atrophy (>50%), the number of myofibers did not correlate with this process. In advanced age, atrophy is accompanied by a decrease in SCs and ßCatenin mRNA, whereas several previously upregulated transcripts were downregulated. The re-expression of embryonic myosin in myofibers and the upregulation of mRNAs encoding the γ-subunit of the nicotinic acetylcholine receptor, the neuronal cell adhesion molecule, and myogenin that begins in late middle age suggest that one mechanism driving sarcopenia is the disruption of neuromuscular connectivity. We conclude that sarcopenia in rats, as in humans, has a long preclinical phase in which muscle undergoes extensive remodeling to maintain muscle mass and function. At later time points, these adaptive mechanisms fail, and sarcopenia becomes clinically manifest.

Epidemiological features of human brucellosis in Tongliao City, Inner Mongolia province, China: a cross-sectional study over an 11-year period (2007-2017).

OBJECTIVES: To describe the epidemiology of human brucellosis in the past decade and provide evidence of disease control in Tongliao city, which is one of the highest-risk areas of human brucellosis in Inner Mongolia province, China. DESIGN: Cross-sectional study. PARTICIPANTS: Clinically and bacteriologically confirmed human brucellosis cases. PRIMARY AND SECONDARY OUTCOME MEASURES: An analysis of the reported cases of human brucellosis during 2007-2017 was carried out to describe the age, sex and occupational distributions of the cases. The time series analysis model and the geographical information system were explored to describe the seasonality and spatiotemporal distribution, respectively, at the county level. RESULTS: A total of 13 938 cases of human brucellosis was collected in Tongliao from 2007 to 2017; the majority was aged 25 years to 59 years (85.4%) and the male-to-female ratio was 2.64:1; most of them were agriculturalists (81.9%) and pastoralists (12.4%). The incidence rates increased dramatically from 9.22/100 000 in 2007 to 69.16/100 000 in 2011 with an annual increase of 14.99%. They decreased during 2012-2016 (annual decrease of 8.37%) and rose again in 2017 (44.32/100 000). The disease peaked during March-July, with a clear periodicity and trend of monthly anterior displacement since 2012. Jarud Banner, the region located in the north-west of Tongliao, had the highest accumulated incidence rate (130.1/100 000) compared with other counties. The high-risk regions were spread from the north-west to the south and east of Tongliao during the past decade. CONCLUSIONS: The prevalence of human brucellosis in Tongliao was aggravated during the past decade and peaked during March-July. High-risk areas were mainly concentrated in the counties with extensive prairies and livestock.

Neuroprotective effect of acute melatonin treatment on hippocampal neurons against irradiation by inhibition of caspase-3.

Neuronal cell apoptosis is associated with various factors that induce neurological damage, including radiation exposure. When administered prior to exposure to radiation, a protective agent may prevent cellular and molecular injury. The present study aimed to investigate whether melatonin exerts a neuroprotective effect by inhibiting the caspase cell death pathway. Male Sprague-Dawley rats were administered melatonin (100 mg/kg body weight) 30 min prior to radiation exposure in red light during the evening. In order to elucidate whether melatonin has a neuroprotective role, immunohistochemistry, terminal deoxynucleotidyl transferase dUTP nick-end labeling, Nissl staining, reverse transcription-quantitative polymerase chain reaction, reactive oxygen species analysis and western blotting were performed. At 24 h post-melatonin treatment, caspase-3 mRNA and protein expression levels were significantly decreased. These results demonstrated that melatonin may protect hippocampal neurons via the inhibition of caspase-3 when exposed to irradiation. Therefore, caspase-3 inhibition serves a neuroprotective and antioxidant role in the interventional treatment of melatonin. The results of the present study suggested that melatonin may have a potential therapeutic effect against irradiation; however, further studies are required in order to elucidate the underlying antioxidant mechanisms.

Resveratrol relieves ischemia-induced oxidative stress in the hippocampus by activating SIRT1.

Resveratrol, a naturally occurring phytoalexin, acts as an activator of sirtuin 1 (SIRT1) and has been shown to have a neuroprotective role in various models. Healthy adult male Sprague-Dawley rats were subjected to cerebral ischemia in order to study the protective effect of resveratrol on the brain following ischemia, and to investigate the effects of SIRT1 activation on the hippocampus. Untreated and resveratrol-treated rats were anesthetized prior to undergoing surgery to induce middle cerebral artery occlusion followed by reperfusion. SIRT1 expression was evaluated by immunohistochemistry, western blotting and reverse transcription-quantitative polymerase chain reaction, and SIRT1 activity was also evaluated. In addition, terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) and Nissl staining assays were conducted and the levels of reactive oxygen species were determined. It was observed that resveratrol significantly decreased the number of TUNEL-positive cells and increased the expression of SIRT1 mRNA in a dose-dependent manner. This was accompanied by increases in SIRT1 protein expression levels and SIRT1 activity. The results demonstrate the neuroprotective and antioxidant effects of resveratrol against ischemia-induced apoptosis in the rat hippocampus.