TNF signaling via TNF receptors does not mediate the effects of short-term exercise on cognition, anxiety and depressive-like behaviors in middle-aged mice.

Background: We recently reported that tumor necrosis factor (TNF) signaling via the TNFR1 and TNFR2 receptors mediates the effects of long-term exercise on locomotion, cognition and anxiety, but not depressive-like behavior. We now investigated whether the TNF signaling via its receptors also mediates the effects of short-term exercise on cognition, anxiety and depressive-like behaviors.

Methods: Thirteen-month-old C57BL/6 (WT), TNF, TNFR1, and TNFR2 mice were provided with 4 weeks of voluntary wheel running followed by behavioral testing using an established behavioral battery.

Genome-wide association study of circulating interleukin 6 levels identifies novel loci.

Interleukin 6 (IL-6) is a multifunctional cytokine with both pro- and anti-inflammatory properties with a heritability estimate of up to 61%. The circulating levels of IL-6 in blood have been associated with an increased risk of complex disease pathogenesis. We conducted a two-staged, discovery and replication meta genome-wide association study (GWAS) of circulating serum IL-6 levels comprising up to 67 428 (ndiscovery = 52 654 and nreplication = 14 774) individuals of European ancestry.

Short-Term Environmental Enrichment is a Stronger Modulator of Brain Glial Cells and Cervical Lymph Node T Cell Subtypes than Exercise or Combined Exercise and Enrichment.

Physical exercise (PE) and environmental enrichment (EE) can modulate immunity. However, the differential effects of short-term PE, EE, and PE + EE on neuroimmune mechanisms during normal aging has not been elucidated. Hence, a cohort of 3-, 8-, and 13-month-old immunologically unchallenged C57BL/6 wild-type mice were randomly assigned to either Control, PE, EE, or PE + EE groups and provided with either no treatment, a running wheel, a variety of plastic and wooden objects alone or in combination with a running wheel for seven weeks, respectively.

Duration of Environmental Enrichment Determines Astrocyte Number and Cervical Lymph Node T Lymphocyte Proportions but Not the Microglial Number in Middle-Aged C57BL/6 Mice.

Environmental enrichment (EE) has been shown to modulate behavior and immunity. We recently reported that both short and long-term EE enhance baseline locomotion and alleviate depressive-like behavior, but only long-term EE affects locomotion adversely in a threatening environment and enhances anxiety-like behavior in middle-age mice. We have now investigated whether the observed changes in behavior after short- and long-term EE were associated with underlying immune changes.

Effects of aging on the motor, cognitive and affective behaviors, neuroimmune responses and hippocampal gene expression.

The known effects of aging on the brain and behavior include impaired cognition, increases in anxiety and depressive-like behaviors, and reduced locomotor activity. Environmental exposures and interventions also influence brain functions during aging. We investigated the effects of normal aging under controlled environmental conditions and in the absence of external interventions on locomotor activity, cognition, anxiety and depressive-like behaviors, immune function and hippocampal gene expression in C57BL/6 mice.

Short-term environmental enrichment, and not physical exercise, alleviate cognitive decline and anxiety from middle age onwards without affecting hippocampal gene expression.

Physical exercise (PE) and environmental enrichment (EE) have consistently been shown to modulate behavior and neurobiological mechanisms. The current literature lacks evidence to confirm the relationship between PE and EE, if any, and whether short-term treatment with PE, EE, or PE+EE could be considered to correct age-related behavioral deficits. Three-, 8-, and 13-month-old C57BL/6 mice were assigned to either PE, EE, or PE+EE treatment groups (n = 12-16/group) for 4 weeks before behavioral testing and were compared to controls.

The effects of short-term and long-term environmental enrichment on locomotion, mood-like behavior, cognition and hippocampal gene expression.

Background: Environmental enrichment (EE) has been shown to modulate behavior and hippocampal gene expression; however, the currently available literature does not explain the differential effects that may relate to the duration of EE.

Aim: To investigate the differential effects of short- and long-term EE on locomotion, anxiety-, depressive- and cognition-like behaviors, and hippocampal gene expression under physiological conditions.

Methods: We assigned either short-term or long-term intervention with respective controls to healthy C57BL/6 mice (n = 12-16/group).

Ceasing exercise induces depression-like, anxiety-like, and impaired cognitive-like behaviours and altered hippocampal gene expression.

Background: Regular exercise can reduce depression-, anxiety-, and impaired cognitive-like behaviours, and upregulate hippocampal genes associated with neuroplasticity. However, the effects of ceasing exercise on depression-, anxiety-, and cognitive-like behaviours, and hippocampal gene expression remain unknown.

Methods: 12-week-old C57BL/6 mice (n = 12-16/group) were randomised to six months of exercise (exercise (EXC)), four months of exercise then two months of no exercise (exercise-cessation (EC)), or no-exercise control (CONT) until aged nine months.

TNF signalling via the TNF receptors mediates the effects of exercise on cognition-like behaviours.

Background: Altered TNF levels are associated with cognitive impairment in depression, schizophrenia, bipolar disorder, and Alzheimer's disease (AD). Exercise improves cognition-like behaviours, reduces the expression of tumour necrosis factor alpha (TNF), and increases expression of the soluble TNF receptors soluble TNFR1 (sTNFR1) and sTNFR2. We suggest TNF and its receptors are involved in cognitive function and dysfunction, and investigate whether exercise mediates its effects on cognitive function via TNF and its receptors.

Exercise related anxiety-like behaviours are mediated by TNF receptor signaling, but not depression-like behaviours.

Unlabelled: Depression can involve disrupted pro-inflammatory TNF signaling via the TNF receptors TNFR1 and TNFR2, or the soluble TNF receptors sTNFR1 and sTNFR2. However, exercise might attenuate pro-inflammatory signaling in depression and related anxiety. We hypothesized that six months voluntary wheel running exercise would improve depression-like and anxiety-like behaviours in WT and TNFR1 mice, but not in TNF and TNFR2 mice compared to their respective control mice.

The effects of aerobic exercise on depression-like, anxiety-like, and cognition-like behaviours over the healthy adult lifespan of C57BL/6 mice.

Preclinical studies have demonstrated exercise improves various types of behaviours such as anxiety-like, depression-like, and cognition-like behaviours. However, these findings were largely conducted in studies utilising short-term exercise protocols, and the effects of lifetime exercise on these behaviours remain unknown. This study investigates the behavioural effects of lifetime exercise in normal healthy ageing C57BL/6 mice over the adult lifespan.

Epigenetic alterations following early postnatal stress: a review on novel aetiological mechanisms of common psychiatric disorders.

Stressor exposure during early life has the potential to increase an individual's susceptibility to a number of neuropsychiatric conditions such as mood and anxiety disorders and schizophrenia in adulthood. This occurs in part due to the dysfunctional stress axis that persists following early adversity impairing stress responsivity across life. The mechanisms underlying the prolonged nature of this vulnerability remain to be established.

Effects of centrally administered etanercept on behavior, microglia, and astrocytes in mice following a peripheral immune challenge.

Peripheral cytokines affect central nervous system (CNS) function, manifesting in symptoms of anxiety and cognitive decline. Although the peripheral blockage of tumor necrosis factor (TNF)-α has been effective in alleviating depression and rheumatoid arthritis, it is yet unknown whether central blockade of TNF-α is beneficial for immune-challenged CNS function. This study investigated the effects of central etanercept administration following a peripheral immune challenge on anxiety-like and cognition-like behaviors and microglia and astrocyte numbers.