Histopathological changes and oxidative damage in type I and type II muscle fibers in rats undergoing paradoxical sleep deprivation.

BACKGROUND: previous studies have shown that muscle atrophy is observed after sleep deprivation (SD) protocols; however, the mechanisms responsible are not fully understood. Muscle trophism can be modulated by several factors, including energy balance (positive or negative), nutritional status, oxidative stress, the level of physical activity, and disuse. The metabolic differences that exist in different types of muscle fiber may also be the result of different adaptive responses. To better understand these mechanisms, we evaluated markers of oxidative damage and histopathological changes in different types of muscle fibers in sleep-deprived rats. METHODS: Twenty male Wistar EPM-1 rats were randomly allocated in two groups: a control group (CTL group; n = 10) and a sleep deprived group (SD group; n = 10). The SD group was submitted to continuous paradoxical SD for 96  h; the soleus (type I fibers) and plantar (type II fiber) muscles were analyzed for histopathological changes, trophism, lysosomal activity, and oxidative damage. Oxidative damage was assessed by lipid peroxidation and nuclear labeling of 8-OHdG. RESULTS: The data demonstrated that SD increased the nuclear labeling of 8-OHdG and induced histopathological changes in both muscles, being more evident in the soleus muscle. In the type I fibers there was signs of tissue degeneration, inflammatory infiltrate and tissue edema. Muscle atrophy was observed in both muscles. The concentration of malondialdehyde, and cathepsin L activity only increased in type I fibers after SD. CONCLUSION: These data indicate that the histopathological changes observed after 96 h of SD in the skeletal muscle occur by different processes, according to the type of muscle fiber, with muscles predominantly composed of type I fibers undergoing greater oxidative damage and catabolic activity, as evidenced by a larger increase in 8-OHdG labeling, lipid peroxidation, and lysosomal activity.

Behavioral and stereological analysis of the prefrontal cortex of rats submitted to chronic alcohol intake.

Alcohol consumption has been identified as a causal factor promoting changes in different molecular and cellular mechanisms resulting in neurodegeneration. This process is specific to certain brain regions and its effects on different areas of the brain can result in a variety of deleterious consequences. The prefrontal cortex (PFC) appears to be particularly sensitive to alcohol-induced neurodegeneration; this region is quite complex, as it is responsible for high order mental processes such as decision making. Thus, it is important to have precise and unbiased data of neuronal morphology parameters to understand the real effects of alcohol on the PFC. This study aimed to investigate alcohol-induced neurodegeneration in the PFC by utilizing behavioral and stereological methods. In the first phase of the study, we utilized eighteen animals, six controls and twelve alcohol-treated, that were submitted to voluntary chronic alcohol ingestion for four or eight weeks. Their brains were analyzed by design-based stereology methods to assess number and volume parameters regarding neuronal integrity in regions of the PFC (prelimbic - PL, infralimbic - IL and anterior cingulate - ACC). In the second phase of the study, six animals were utilized as controls and eight animals were submitted to the same alcohol ingestion protocol and to a behavioral decision-making test. In conclusion, our findings indicate that chronic alcohol consumption promotes a decrease in volume in the prelimbic and in the anterior cingulate, a decrease of mean neuronal volume in the anterior cingulate cortex and a decrease of total volume of neurons in the IL area. We did not observe changes in decision-making behavior in either of the two periods of alcohol intake. This shows that morphological changes occur in specific regions of the prefrontal cortex, a noble area of cognitive functions, induced by chronic alcohol consumption.

Environmental enrichment decreases avoidance responses in the elevated T-maze and delta FosB immunoreactivity in anxiety-related brain regions.

Environmental enrichment (EE) is an animal management technique, which seems to improve adaptation to the experimental conditions of housing in laboratory animals. Previous studies have pointed to different beneficial effects of the procedure in the treatment of several disorders, including psychiatric conditions such as depression. The anxiolytic effects induced by EE, on the other hand, are not as clear. In fact, it has been proposed that EE acts as a mild stressor agent. To better understand the relationship of EE with anxiety-related responses, the present study exposed rats to one week of EE and subsequently tested these animals in the inhibitory avoidance and escape tasks of the elevated T-maze (ETM). In clinical terms, these responses have been respectively related to generalized anxiety and panic disorder. All animals were tested in an open field, immediately after the ETM, for locomotor activity assessment. Additionally, analysis of delta FosB protein immunoreactivity (FosB-ir) was used to map areas activated by EE exposure and plasma corticosterone measurements were performed. The results obtained demonstrate that exposure to EE for one week impaired avoidance responses, an anxiolytic-like effect, without altering escape reactions. Also, in animals submitted to the avoidance task EE exposure decreased FosB-ir in the cingulate cortex, dorsolateral and intermediate lateral septum, hippocampus (cornus of Ammon), anterior and dorsomedial hypothalamus, medial and basolateral amygdala and ventral region of the dorsal raphe nucleus. Although no behavioral differences were observed in animals submitted to the escape task, EE exposure also decreased FosB-ir in the cingulate cortex, hippocampus (dentate gyrus), lateral amygdala, paraventricular, anterior and ventromedial hypothalamus, dorsomedial periaqueductal gray and ventral and dorsal region of the dorsal raphe. No changes in corticosterone levels, however, were observed. These results contribute to a better understanding of the effects of EE on anxiety.