Exercise and the brain: a slap on the HAND

摘要: Regular exercise is good for the brain. It improves mood, lessens anxiety and provides a hedge against depression (Salmon, 2001). Exercise can also improve cognitive performance in healthy animals human subjects, delay disease onset and/or slow its progression animal models of Alzheimer's (Cotman Berchtold, 2002; Mattson, 2012). The results from epidemiological interventional studies suggest that regular reduce risk age-related impairment dementia (Voss et al., 2011). mechanisms by which enhances preserves brain function involve stimulation dendrite growth, strengthening existing synapses formation new synapses. In addition, stimulates neurogenesis (the production neurons stem cells) dentate gyrus hippocampus, some newly-generated integrate into hippocampal neuronal circuits as they receive synaptic inputs entorhinal cortex basal forebrain cholinergic (Vivar Interestingly, produced response to appear play key role spatial pattern separation, type learning memory mediated hippocampus (Creer 2010). Two reported this issue Journal NeuroVirology provide evidence counteract adverse effects immunodeficiency virus (HIV) infection on structural integrity, function. HIV-associated neurocognitive disorders (HAND) has become major concern many HIV AIDS patients health care providers (Clark Cohen, 2010). While protease inhibitor cocktail therapy been highly effective prolonging lives patients, continues adversely affect Because does not infect neurons, current understanding pathogenesis HAND invokes viral reservoir harbored within glial cells. Neurotoxic proteins are then released infected cells damage mechanism involving disruption cellular Ca2+ homeostasis ‘excitotoxicity’; coat protein gp120 transactivator Tat have each shown endanger promoting overload (Mattson 2005). microglial release pro-inflammatory cytokines, reactive oxygen species excitotoxins likely contribute degeneration (Gupta Moreover, reduces active form brain-derived neurotrophic factor (BDNF), suggesting possibility reduced trophic support (Bachis 2012). To directly determine if how affects neuropathogenic processes relevant HAND, Lee al. (2013) employed transgenic mouse model expression driven an astrocyte (GFAP) promoter. These (gp120Tg) mice exhibit impaired outgrowth compared non-transgenic control mice. When gp120Tg were provided running wheels their cages 3-20 days there was significant increase proliferation neural progenitor effect correlated positively with daily distance. dendrites granule longer runners sedentary However, when had run 10 deprived subsequent days, same level never run. known BDNF found increased levels mice, contributed beneficial growth (Lee Li 2008). suppressed activation cyclin-dependent kinase 5 (Cdk5), previous mediates apoptosis experimental 2000), well neurotoxic supernatants HIV-infected macrophages (Wang 2007). findings direct plasticity, underlying involves bolstering suppression apoptotic biochemical cascades 2013). plasticity evaluated runner so it remains be established whether reverse deficits HAND. Will prevent or humans will ameliorate those already diagnosed HAND? study journal Dufour relationship between over 300 subjects. Based upon exercised vigorously not, subjects divided groups. completed test battery covered domains often including working memory, verbal fluency, information processing speed, recall executive After accounting several potential confounding factors, authors overall group significantly superior group. Among tested, associated better speed. Previous that, other patient populations, lessen (Hand 2009). emerging therefore suggests individuals. Future intervention trials required what extent programs patients. Collectively, raise questions regarding molecular changes occur impact process. Does load brain? If so, relative contributions exposure versus protection proteins? addition outgrowth, plays roles formation, maintenance (Lu number size regions patients? Brain imaging (fMRI PET) mild impairment, prodromal disease, abnormalities network activity energy metabolism deficit (Kapogiannis Is resting state default mode Recent reports may indeed true (Thomas 2013; Towgood 2012). Finally, benefit interventions production, enhance performance? Two such intermittent fasting (Mattson, 2012) intellectual challenges (Scarmeas Stern, 2004). Will additive benefits combined fasting, challenges? pharmacological agents regard, antidepressants inhibit serotonin norepinephrine reuptake at (Castren Rantamaki, 2010) could tested clinical patients. pointing disease-modifying optimism currently available, future treatments target specific pathogenic, neuroplasticity-impairing actions developed.