CONTEXT: Physical activity can improve cognitive and mental health, but the underlying mechanisms have not been established. OBJECTIVE: To present a conceptual model explaining the mechanisms for the effect of physical activity on cognitive and mental health in young people and to conduct a systematic review of the evidence. DATA SOURCES: Six electronic databases (PubMed, PsycINFO, SCOPUS, Ovid Medline, SportDiscus, and Embase) were used. STUDY SELECTION: School-, home-, or community-based physical activity intervention or laboratory-based exercise interventions were assessed. Studies were eligible if they reported statistical analyses of changes in the following: (1) cognition or mental health; and (2) neurobiological, psychosocial, and behavioral mechanisms. DATA EXTRACTION: Data relating to methods, assessment period, participant characteristics, intervention type, setting, and facilitator/delivery were extracted. RESULTS: Twenty-five articles reporting results from 22 studies were included. Mechanisms studied were neurobiological (6 studies), psychosocial (18 studies), and behavioral (2 studies). Significant changes in at least 1 potential neurobiological mechanism were reported in 5 studies, and significant effects for at least 1 cognitive outcome were also found in 5 studies. One of 2 studies reported a significant effect for self-regulation, but neither study reported a significant impact on mental health. LIMITATIONS: Small number of studies and high levels of study heterogeneity. CONCLUSIONS: The strongest evidence was found for improvements in physical self-perceptions, which accompanied enhanced self-esteem in the majority of studies measuring these outcomes. Few studies examined neurobiological and behavioral mechanisms, and we were unable to draw conclusions regarding their role in enhancing cognitive and mental health.

Reactive astrocytes are thought to protect the penumbra during brain ischemia, but direct evidence has been lacking due to the absence of suitable experimental models. Previously, we generated mice deficient in two intermediate filament (IF) proteins, glial fibrillary acidic protein (GFAP) and vimentin, whose upregulation is the hallmark of reactive astrocytes. GFAP^−/−Vim^−/− mice exhibit attenuated posttraumatic reactive gliosis, improved integration of neural grafts, and posttraumatic regeneration. Seven days after middle cerebral artery (MCA) transection, infarct volume was 210 to 350% higher in GFAP^−/−Vim^−/− than in wild-type (WT) mice; GFAP^−/−, Vim^−/− and WT mice had the same infarct volume. Endothelin B receptor (ET_BR) immunoreactivity was strong on cultured astrocytes and reactive astrocytes around infarct in WT mice but undetectable in GFAP^−/−Vim^−/− astrocytes. In WT astrocytes, ET_BR colocalized extensively with bundles of IFs. GFAP^−/−Vim^−/− astrocytes showed attenuated endothelin-3-induced blockage of gap junctions. Total and glutamate transporter-1 (GLT-1)-mediated glutamate transport was lower in GFAP^−/−Vim^−/− than in WT mice. DNA array analysis and quantitative real-time PCR showed downregulation of plasminogen activator inhibitor-1 (PAI-1), an inhibitor of tissue plasminogen activator. Thus, reactive astrocytes have a protective role in brain ischemia, and the absence of astrocyte IFs is linked to changes in glutamate transport, ET_BR-mediated control of gap junctions, and PAI-1 expression.

Traditionally, microglia have been considered to act as macrophages of the central nervous system. While this concept still remains true it is also becoming increasingly apparent that microglia are involved in a host of nonimmunological activities, such as monitoring synaptic function and maintaining synaptic integrity. It has also become apparent that microglia are exquisitely sensitive to perturbation by environmental challenges. The aim of the current review is to critically examine the now substantial literature that has developed around the ability of acute, sub-chronic and chronic stressors to alter microglial structure and function. The vast majority of studies have demonstrated that stress promotes significant structural remodelling of microglia, and can enhance the release of pro-inflammatory cytokines from microglia. Mechanistically, many of these effects appear to be driven by traditional stress-linked signalling molecules, namely corticosterone and norepinephrine. The specific effects of these signalling molecules are, however, complex as they can exert both inhibitory and suppressive effects on microglia depending upon the duration and intensity of exposure. Importantly, research has now shown that these stress-induced microglial alterations, rather than being epiphenomena, have broader behavioural implications, with the available evidence implicating microglia in directly regulating certain aspects of cognitive function and emotional regulation.

During early adulthood, a phase in which the central nervous system displays considerable plasticity and in which important cognitive traits are shaped, the effects of exercise on cognition remain poorly understood. We performed a cohort study of all Swedish men born in 1950 through 1976 who were enlisted for military service at age 18 ( N = 1,221,727). Of these, 268,496 were full-sibling pairs, 3,147 twin pairs, and 1,432 monozygotic twin pairs. Physical fitness and intelligence performance data were collected during conscription examinations and linked with other national databases for information on school achievement, socioeconomic status, and sibship. Relationships between cardiovascular fitness and intelligence at age 18 were evaluated by linear models in the total cohort and in subgroups of full-sibling pairs and twin pairs. Cardiovascular fitness, as measured by ergometer cycling, positively associated with intelligence after adjusting for relevant confounders (regression coefficient b = 0.172; 95% CI, 0.168–0.176). Similar results were obtained within monozygotic twin pairs. In contrast, muscle strength was not associated with cognitive performance. Cross-twin cross-trait analyses showed that the associations were primarily explained by individual specific, non-shared environmental influences (≥80%), whereas heritability explained <15% of covariation. Cardiovascular fitness changes between age 15 and 18 y predicted cognitive performance at 18 y. Cox proportional-hazards models showed that cardiovascular fitness at age 18 y predicted educational achievements later in life. These data substantiate that physical exercise could be an important instrument for public health initiatives to optimize educational achievements, cognitive performance, as well as disease prevention at the society level.