Long-term environmental modifications affect BDNF concentrations in rat hippocampus, but not in serum.

The role of mBDNF on the beneficial effects of cognitive stimulation on the brain remains controversial, as well as the potential of peripheral mBDNF as a biomarker of environmental effects on its central status. We investigated the effect of different environmental conditions on recognition memory, proBDNF, mBDNF and synaptophysin levels in the hippocampus, and on mBDNF levels in blood. Male Wistar rats (6 and 17 months-old) were assigned to cognitively enriched (EE), standard (SE) and impoverished (IE) environmental conditions for twelve weeks. Novel object recognition was performed at week 10. When the animals were 9 and 20-months old, hippocampus was collected for mBDNF, proBDNF and synaptophysin analysis; serum was analyzed for mBDNF levels. The cognitively EE improved recognition memory, resulted in a trend to increased hippocampal mBDNF and augmented synaptophysin levels. Accordingly, hippocampal mBDNF, proBDNF and synaptophysin were significantly higher in EE than IE animals. Hippocampal mBDNF was positively correlated to proBDNF, cellular and behavioral plasticity markers. No effect of age was seen on the studied variables. Moreover, no significant effects of EE or IE on serum mBDNF were observed. Serum mBDNF also failed to correlate with hippocampal mBDNF, proBDNF and with the cellular and behavioral plasticity markers. These findings indicate that mBDNF is involved in neuronal and behavioral plasticity mechanisms induced by cognitively enriched environments, and that peripheral mBDNF may not always be a reliable biomarker of the effects of environmental settings on central mBDNF and plasticity, which is of special interest from a translational research perspective.

Social isolation and social support at adulthood affect epigenetic mechanisms, brain-derived neurotrophic factor levels and behavior of chronically stressed rats.

Epigenetic modulation of brain-derived neurotrophic factor (BDNF) provides one possible explanation for the dysfunctions induced by stress, such as psychiatric disorders and cognitive decline. Interestingly, social support can be protective against some of these effects, but the mechanisms of social buffering are poorly understood. Conversely, early isolation exacerbates the responses to stressors, although its effects in adulthood remain unclear. This study investigated the effects of social isolation and social buffering on hippocampal epigenetic mechanisms, BDNF levels and behavioral responses of chronically stressed young adult rats. Male Wistar rats (3 months) were assigned to accompanied (paired) or isolated housing. After one-month half of each group was submitted to a chronic unpredictable stress (CUS) protocol for 18 days. Among accompanied animals, only one was exposed to stress. Behavioral analysis encompassed the Open field, plus maze and inhibitory avoidance tasks. Hippocampal H3K9 and H4K12 acetylation, HDAC5 expression and BDNF levels were evaluated. Isolated housing increased HDAC5 expression, decreased H3K9 and H4K12 acetylation, reduced BDNF levels, and impaired long-term memory. Stress affected weight gain, induced anxiety-like behavior and decreased AcK9H3 levels. Interactions between housing conditions and social stress were seen only for HDAC5 expression, which showed a further increase in the isolated + CUS group but remained constant in accompanied animals. In conclusion, social isolation at adulthood induced epigenetic alterations and exacerbated the effects of chronic stress on HDAC5. Notwithstanding, social support counteracted the adverse effects of stress on HDAC5 expression.

Mental health in familial caregivers of Alzheimer's disease patients: are the effects of chronic stress on cognition inevitable?

Familial caregivers of Alzheimer's disease (AD) patients experience an emotional and physical burden which characterizes a chronic stress condition. The resulting hypothalamic-pituitary-adrenal axis dysfunction favors an imbalance of neurotoxic/neuroprotective factors and causes cognitive impairments, increasing the caregivers' risk for cognitive decline and compromising their ability to provide adequate care of the patient. Therefore, the present study aimed to investigate the reversibility of the cognitive impairments of familial caregivers of AD patients during their caregiving-related chronic stress condition. Thirty-three caregivers (61.42 + 2.68 years; 27 women) and thirty-four controls (57.91 ± 2.16 years, 20 women) were evaluated for their cognitive functioning (attention, executive function, processing speed and memory) with a neuropsychological battery (Digit-span, Trail Making, Stroop and the Logical Memory tests). Subjects' cortisol/dehydroepiandrosterone (DHEA) ratios were determined by radioimmunoassay, and their brain-derived neurotrophic factor (BDNF) levels were analyzed by ELISA. An incidental contextual memory task, with or without an associative encoding instruction, was used to investigate if caregivers have a cognitive reserve prone to rehabilitation. The contextual memory impairment of caregivers was associated with prefrontal and hippocampal cognitive dysfunctions, alterations of the cortisol/DHEA ratio and lower BDNF levels. Even so, the contextual memory impairment could be improved by the associative encoding condition. This study suggests that the cognitive impairments of caregivers are not necessarily irreversible, as indicated by the results obtained for contextual memory, which could be improved despite the ongoing chronic stress and associated hormonal and neurotrophin dysfunctions. Lay summary The support of a relative with Alzheimer's Disease submits the familial caregivers to a chronic stress condition that increases their own risk of cognitive decline. This study suggests that, irrespective to their alterations on cortisol/DHEA ratio and BDNF levels, caregivers have a cognitive reserve that could probably be engaged to limit the negative effects of chronic stress on cognition.

Multimodal physical activity increases brain-derived neurotrophic factor levels and improves cognition in institutionalized older women.

Physical activity has been proposed as a promising intervention to improve cognition and decrease the risk of dementia in older adults. Brain-derived neurotrophic factor (BDNF) appears to mediate, at least partially, these effects of exercise. However, intervention studies of the effects of multimodal exercises on cognition and BDNF levels are scarce and composed by small samples. Thus, the generalization of the conclusions of these studies depends on the reproducibility of the results. In order to contribute to the knowledge on the field, the present study evaluated the effects of a physical activity intervention composed by muscle strengthening and aerobic conditioning on BDNF levels and cognition in older women. Independent and non-demented subjects (≥75 years) were assigned to a 3-month physical activity intervention (n = 22, 60 min exercise sessions three times a week) or to a control condition (n = 10, no exercise). Clinical (anxiety and depression symptoms), neuropsychological (Digit Span, Stroop, Trail Making, and Contextual Memory tests), physical (upper and lower limb strength, aerobic conditioning), and physiological (serum BDNF) parameters were evaluated immediately before, 1 month, and 3 months after starting intervention. Results indicated that controls had stable levels for all measured variables, whereas the intervention group improved on physical fitness, depressive symptoms, cognitive performance, and BDNF levels. Moreover, a linear regression identified an association between aerobic conditioning and BDNF levels. In conclusion, combined muscle strengthening and aerobic conditioning was able to improve cognitive performance and increase BDNF levels. Aerobic conditioning seems to be an important mediator of these outcomes.

Age Effects on Cognitive and Physiological Parameters in Familial Caregivers of Alzheimer's Disease Patients.

OBJECTIVES: Older familial caregivers of Alzheimer's disease patients are subjected to stress-related cognitive and psychophysiological dysfunctions that may affect their quality of life and ability to provide care. Younger caregivers have never been properly evaluated. We hypothesized that they would show qualitatively similar cognitive and psychophysiological alterations to those of older caregivers. METHOD: The cognitive measures of 17 young (31-58 years) and 18 old (63-84 years) caregivers and of 17 young (37-57 years) and 18 old (62-84 years) non-caregiver controls were evaluated together with their salivary cortisol and dehydroepiandrosterone (DHEA) levels, as measured by radioimmunoassays and ELISA assays of brain-derived neurotrophic factor (BDNF) in serum. RESULTS: Although younger caregivers had milder impairments in memory and executive functions than older caregivers, their performances fell to the same or lower levels as those of the healthy older controls. Decreases in DHEA and BDNF levels were correlated with the cognitive dysfunctions observed in the older and younger caregivers, respectively. Cortisol at 10PM increased in both caregiver groups. DISCUSSION: Younger caregivers were prone to cognitive impairments similar to older caregivers, although the degree and the neuropsychological correlates of the cognitive dysfunctions were somewhat different between the two groups. This work has implications for caregiver and care-recipient health and for research on the neurobiology of stress-related cognitive dysfunctions.

Could BDNF be involved in compensatory mechanisms to maintain cognitive performance despite acute sleep deprivation? An exploratory study.

BACKGROUND: Neuroimaging studies suggest that acute sleep deprivation can lead to adaptations, such as compensatory recruitment of cerebral structures, to maintain cognitive performance despite sleep loss. However, the understanding of the neurochemical alterations related to these adaptations remains incomplete. OBJECTIVE: Investigate BDNF levels, cognitive performance and their relations in healthy subjects after acute sleep deprivation. METHODS: Nineteen sleep deprived (22.11±3.21years) and twenty control (25.10±4.42years) subjects completed depression, anxiety and sleep quality questionnaires. Sleep deprived group spent a full night awake performing different playful activities to keep themselves from sleeping. Attention, response inhibition capacity and working memory (prefrontal cortex-dependent) were assessed with Stroop and Digit Span tests. Declarative memory (hippocampus-dependent) was assessed with Logical Memory test. Serum BDNF was measured by sandwich ELISA. Data were analyzed with independent samples T-test, ANOVA, ANCOVA and curve estimation regressions. p<0.05 was deemed statistically significant. RESULTS: The sleep deprived group showed higher BDNF levels and normal performance on attention, response inhibition capacity and working memory. However, declarative memory was impaired. A sigmoidal relation between BDNF and Stroop Test scores was found. CONCLUSIONS: Increased BDNF could be related, at least in part, to the maintenance of normal prefrontal cognitive functions after sleep deprivation. This potential relation should be further investigated.

Low-level laser therapy (LLLT) prevents oxidative stress and reduces fibrosis in rat traumatized Achilles tendon.

BACKGROUND AND OBJECTIVES: The present study investigated the effects of low-level laser therapy (LLLT) on oxidative stress and fibrosis in an experimental model of Achilles tendon injury induced by a single impact trauma. STUDY DESIGN/MATERIALS AND METHODS: Male Wistar rats were randomly divided into four groups (n = 8): control, trauma, trauma+LLLT for 14 days, and trauma+LLLT for 21 days. Achilles tendon traumatism was produced by dropping down a load with an impact kinetic energy of 0.544 J. A low level Ga-As laser was applied with a 904 nm wavelength, 45 mW average power, 5 J/cm(2) dosage, for 35 seconds duration, continuously. Studies were carried out at day 21. RESULTS: Histology showed a loss of normal architecture, with inflammatory reaction, angiogenesis, vasodilatation, and extracellular matrix formation after trauma. This was accompanied by a significant increase in collagen concentration when compared the control group. Oxidative stress, measured by the concentration of thiobarbituric acid reactive substances and hydroperoxyde-initiated chemiluminiscence, was also significantly increased in the trauma group. Administration of LLLT for 14 or 21 days markedly alleviated histological abnormalities reduced collagen concentration and prevented oxidative stress. Superoxide dismutase activity was significantly increased by LLLT treatment over control values. CONCLUSION: LLLT by Ga-As laser reduces histological abnormalities, collagen concentration, and oxidative stress in an experimental model of Achilles tendon injury. Reduction of fibrosis could be mediated by the beneficial effects on the oxidant/antioxidant balance.