Acute exposure to low-level light at night is sufficient to induce neurological changes and depressive-like behavior.

The advent and wide-spread adoption of electric lighting over the past century has profoundly affected the circadian organization of physiology and behavior for many individuals in industrialized nations; electric lighting in homes, work environments, and public areas have extended daytime activities into the evening, thus, increasing night-time exposure to light. Although initially assumed to be innocuous, chronic exposure to light at night (LAN) is now associated with increased incidence of cancer, metabolic disorders, and affective problems in humans. However, little is known about potential acute effects of LAN. To determine whether acute exposure to low-level LAN alters brain function, adult male, and female mice were housed in either light days and dark nights (LD; 14 h of 150 lux:10 h of 0 lux) or light days and low level light at night (LAN; 14 h of 150 lux:10 h of 5 lux). Mice exposed to LAN on three consecutive nights increased depressive-like responses compared to mice housed in dark nights. In addition, female mice exposed to LAN increased central tendency in the open field. LAN was associated with reduced hippocampal vascular endothelial growth factor-A (VEGF-A) in both male and female mice, as well as increased VEGFR1 and interleukin-1ß mRNA expression in females, and reduced brain derived neurotrophic factor mRNA in males. Further, LAN significantly altered circadian rhythms (activity and temperature) and circadian gene expression in female and male mice, respectively. Altogether, this study demonstrates that acute exposure to LAN alters brain physiology and can be detrimental to well-being in otherwise healthy individuals.

Clearing the fog: a review of the effects of dietary omega-3 fatty acids and added sugars on chemotherapy-induced cognitive deficits.

Cancer treatments such as chemotherapy have been an important part of extending survival in women diagnosed with breast cancer. However, chemotherapy can cause potentially toxic side effects in the brain that impair memory, verbal fluency, and processing speed in up to 30% of women treated. Women report that post-chemotherapy cognitive deficits negatively impact quality of life and may last up to ten years after treatment. Mechanisms underlying these cognitive impairments are not fully understood, but emerging evidence suggests that chemotherapy induces structural changes in the brain, produces neuroinflammation, and reduces adult hippocampal neurogenesis. Dietary approaches that modify inflammation and neurogenesis are promising strategies for reducing chemotherapy-induced cognitive deficits in breast cancer survivors. In this review, we describe the cognitive and neuronal side effects associated with commonly used chemotherapy treatments for breast cancer, and we focus on the often opposing actions of omega-3 fatty acids and added sugars on cognitive function, neuroinflammation, and adult hippocampal neurogenesis. Omega-3 fatty acids administered concurrently with doxorubicin chemotherapy have been shown to prevent depressive-like behaviors and reduce neuroinflammation, oxidative stress, and neural apoptosis in rodent models. In contrast, diets high in added sugars may interact with n-3 FAs to diminish their anti-inflammatory activity or act independently to increase neuroinflammation, reduce adult hippocampal neurogenesis, and promote cognitive deficits. We propose that a diet rich in long-chain, marine-derived omega-3 fatty acids and low in added sugars may be an ideal pattern for preventing or alleviating neuroinflammation and oxidative stress, thereby protecting neurons from the toxic effects of chemotherapy. Research testing this hypothesis could lead to the identification of modifiable dietary choices to reduce the long-term impact of chemotherapy on the cognitive functions that are important to quality of life in breast cancer survivors.

Affective responses to self-selected and imposed walking in inactive women with high stress: a pilot study.

AIM: The primary purpose was to examine affective responses and future intentions in response to self-selected and imposed-intensity walking in inactive women with high levels of stress. The secondary purpose was to examine potential psychobiological variables (cortisol responses and self-efficacy) associated with changes in affective states. METHODS: Nineteen participants (age=23.58 ± 5.30 yr) completed three trials of treadmill walking at self-selected intensity, 10% above and 10% below relative self-selected intensity. Walking duration was determined to expend 150 kcal. Affective responses and salivary cortisol were measured prior to, during, and following walking sessions. Self-efficacy was also measured during and post-walking. Future intention was measured post walking. RESULTS: Affect and self-efficacy improved significantly over time at all walking intensity conditions. Moreover, selected affect variables were improved at self-selected but not at imposed intensity during and post walking. No significant associations were observed between affect, self-efficacy and cortisol levels. However, affect and self-efficacy did significantly predict future intentions. CONCLUSION: Treadmill walking at intensities proximal to and lower than ventilatory threshold were associated with positive affective responses during and after walking in women with high levels of stress. Self-selected intensity may be effective for eliciting more favorable experiences during and following acute bouts of exercise, and promote future intentions for exercise. Findings provide partial support for self-efficacy during exercise as a potential mechanism for positive affective responses, especially at self-selected intensity.

Social interaction prevents the development of depressive-like behavior post nerve injury in mice: a potential role for oxytocin.

OBJECTIVE: To examine the salubrious role of social interaction in modulating the development of allodynia (increased sensitivity to typically innocuous physical stimuli) and depressive-like behavior post peripheral nerve injury in mice. The determination of potential mechanisms that mediate social influences on the behavioral and physiological response to peripheral nerve injury. METHODS: Mice were pair housed or socially isolated for 2 weeks before spared nerve injury (SNI). Animals were cannulated; socially isolated animals were centrally treated with oxytocin; and socially paired animals were centrally treated with an oxytocin receptor antagonist. Animals were subsequently monitored for the development of mechanical allodynia and depressive-like behavior, and tissue was collected for analysis of the central levels of the cytokine interleukin 1 beta (IL-1beta). RESULTS: Depressive-like behavior was assessed via the Porsolt forced swim test, developed only among socially isolated mice with nerve injury. Socially isolated mice with nerve injury also were the only experimental group to exhibit increased frontal cortex IL-1beta gene expression on day 7 post injury. Moreover, central treatment of socially isolated mice with oxytocin, a neuropeptide associated with social bonding, attenuated the effects of SNI on depressive-like behavior and reduced frontal cortex IL-1beta protein levels in socially isolated animals. Conversely, pair-housed animals treated with a selective oxytocin receptor antagonist developed depressive-like behavior equivalent to that of socially isolated animals and displayed increased IL-1beta protein levels within the frontal cortex. CONCLUSION: These data suggest that social interaction significantly alters the affective and neuroinflammatory responses to SNI through a mechanism that could involve oxytocin.

Transcardial perfusion is not required to accurately measure cytokines within the brain.

BACKGROUND: Cytokines are key signaling molecules within the immune system that regulate a host's response to pathogens and neuronal damage. Aberrant cytokine signaling has been implicated in many neurological diseases. Therefore, accurately measuring cytokine concentrations within the brain is crucial. NEW METHOD: This study demonstrates that removing blood within brain vasculature via saline perfusion does not alter brain parenchymal cytokine protein concentrations or mRNA expression. RESULTS: Hippocampal protein and mRNA data demonstrate that brain parenchymal cytokine concentrations do not significantly differ based on the method of euthanasia (i.e., perfusion or no perfusion). These results are consistent within naive and immune challenged mice. COMPARISON WITH EXISTING METHOD: Due to the potential of cytokine contamination from circulating blood, it is believed that transcardial perfusion is required for accurate measurement of cytokine concentrations and gene expression within the brain. However, our data indicate that cytokine concentrations are unaffected by not perfusing mice with saline prior to tissue collection. CONCLUSIONS: Brain cytokine concentrations are unaffected by perfusing with saline prior to tissue collection; this holds true regardless of immune status (homeostatic or immune challenged), suggesting that this time-consuming step may be unnecessary.

Cardiac arrest/cardiopulmonary resuscitation augments cell-mediated immune function and transiently suppresses humoral immune function.

Immune system activation has implications for cerebrovascular health, but little is known about the function of the immune system after a major cerebrovascular event, such as cardiac arrest and cardiopulmonary resuscitation (CA/CPR). Cardiac arrest and cardiopulmonary resuscitation damages the hippocampus, an important component of the hypothalamic-pituitary-adrenal (HPA) axis, and alterations in HPA axis activity can affect immune function. We tested the hypothesis that CA/CPR (approximately 8 mins) would cause HPA axis dysregulation and alter the delayed type hypersensitivity (DTH) response to antigenic challenge. We also assessed the primary and secondary antibody response of mice exposed to CA/CPR. Of the mice exposed to CA/CPR, half had brains protected by hypothermia to isolate the effects of the CA/CPR procedure from the effects of CA/CPR-induced neuronal damage. Cardiac arrest and cardiopulmonary resuscitation-induced neuronal damage resulted in a persistent elevation of blood corticosterone concentration and a concomitant augmentation of the DTH response to antigenic challenge. Furthermore, immune activation before CA/CPR decreased survival after global ischemia. These data highlight the potential impact of neuronal damage on cell-mediated immune function and the role of humoral immune activation in outcome after global ischemia.