Anxiety-Like Behaviors in Mice Unmasked: Revealing Sex Differences in Anxiety Using a Novel Light-Heat Conflict Test.

Anxiety and chronic pain afflict hundreds of millions worldwide. Anxiety and pain are more prevalent in females compared to males. Unfortunately, robust sex differences in human anxiety are not recapitulated in rodent tests, and results from rodent pain studies frequently fail to translate clinically.

Effects of dim light at night in C57BL/6 J mice on recovery after spinal cord injury.

Spinal cord injury (SCI) can cause long-lasting locomotor deficits, pain, and mood disorders. Anatomical and functional outcomes are exacerbated by inflammation after SCI, which causes secondary damage. One promising target after SCI is manipulating the circadian system, which optimizes biology and behavior for time of day - including neuroimmune responses and mood-related behaviors.

Effects of dim light at night in C57BL/6J mice on recovery after spinal cord injury.

Spinal cord injury (SCI) can cause long-lasting locomotor deficits, pain, and mood disorders. Anatomical and functional outcomes are exacerbated by inflammation after SCI, which causes secondary damage. One promising target after SCI is manipulating the circadian system, which optimizes biology and behavior for time of day - including neuroimmune responses and mood-related behaviors.

Microglia depletion ameliorates neuroinflammation, anxiety-like behavior, and cognitive deficits in a sex-specific manner in Rev-erbα knockout mice.

The circadian system is an evolutionarily adaptive system that synchronizes biological and physiological activities within the body to the 24 h oscillations on Earth. At the molecular level, circadian clock proteins are transcriptional factors that regulate the rhythmic expression of genes involved in numerous physiological processes such as sleep, cognition, mood, and immune function. Environmental and genetic disruption of the circadian clock can lead to pathology.

Circadian Regulation of the Neuroimmune Environment Across the Lifespan: From Brain Development to Aging.

Circadian clocks confer 24-h periodicity to biological systems, to ultimately maximize energy efficiency and promote survival in a world with regular environmental light cycles. In mammals, circadian rhythms regulate myriad physiological functions, including the immune, endocrine, and central nervous systems. Within the central nervous system, specialized glial cells such as astrocytes and microglia survey and maintain the neuroimmune environment.

Spinal cord injury in mice amplifies anxiety: A novel light-heat conflict test exposes increased salience of anxiety over heat.

Spinal cord injury (SCI) predisposes individuals to anxiety and chronic pain. Anxiety- and pain-like behavior after SCI can be tested in rodents, yet commonly used tests assess one variable and may not replicate effects of SCI or sex differences seen in humans. Thus, novel preclinical tests should be optimized to better evaluate behaviors relating to anxiety and pain.

WWOX P47T partial loss-of-function mutation induces epilepsy, progressive neuroinflammation, and cerebellar degeneration in mice phenocopying human SCAR12.

WWOX gene loss-of-function (LoF) has been associated with neuropathologies resulting in developmental, epileptic, and ataxic phenotypes of varying severity based on the level of WWOX dysfunction. WWOX gene biallelic germline variant p.Pro47Thr (P47T) has been causally associated with a new form of autosomal recessive cerebellar ataxia with epilepsy and intellectual disability (SCAR12, MIM:614322).

Neuroimmunology of healthy brain aging.

Aging involves progressive deterioration away from homeostasis. Whereas the healthy adult brain maintains neuroimmune cells in a surveillant and homeostatic state, aged glial cells have a hyperreactive phenotype. These age-related pro-inflammatory biases are driven in part by cell-intrinsic factors, including increased cell priming and pro-inflammatory cell states.

The neuroimmune system - Where aging and excess alcohol intersect.

As the percentage of the global population over age 65 grows, and with it a subpopulation of individuals with alcohol use disorder (AUD), understanding the effect of alcohol on the aged brain is of utmost importance. Neuroinflammation is implicated in both natural aging as well as alcohol use, and its role in alterations to brain morphology and function may be exacerbated in aging individuals who drink alcohol to excess. The neuroimmune response to alcohol in aging is complex.

Immunization with a heat-killed preparation of Mycobacterium vaccae NCTC 11659 enhances auditory-cued fear extinction in a stress-dependent manner.

Stress-related psychiatric disorders including anxiety disorders, mood disorders, and trauma and stressor-related disorders, such as posttraumatic stress disorder (PTSD), affect millions of people world-wide each year. Individuals with stress-related psychiatric disorders have been found to have poor immunoregulation, increased proinflammatory markers, and dysregulation of fear memory. The "Old Friends" hypothesis proposes that a lack of immunoregulatory inputs has led to a higher prevalence of inflammatory disorders and stress-related psychiatric disorders, in which inappropriate inflammation is thought to be a risk factor.

Distinct immune and transcriptomic profiles in dominant versus subordinate males in mouse social hierarchies.

Social status is a critical factor determining health outcomes in human and nonhuman social species. In social hierarchies with reproductive skew, individuals compete to monopolize resources and increase mating opportunities. This can come at a significant energetic cost leading to trade-offs between different physiological systems.

Mycobacterium vaccae immunization in rats ameliorates features of age-associated microglia activation in the amygdala and hippocampus.

Aging and reduced exposure to environmental microbes can both potentiate neuroinflammatory responses. Prior studies indicate that immunization with the immunoregulatory and anti-inflammatory bacterium, Mycobacterium vaccae (M. vaccae), in aged rats limits neuroimmune activation and cognitive impairments.

Chronic circadian phase advance in male mice induces depressive-like responses and suppresses neuroimmune activation.

Altered working and sleeping schedules during the COVID-19 pandemic likely impact our circadian systems. At the molecular level, clock genes form feedback inhibition loops that control 24-hr oscillations throughout the body. Importantly, core clock genes also regulate microglia, the brain resident immune cell, suggesting circadian regulation of neuroimmune function.

Aging and miR-155 in mice influence survival and neuropathic pain after spinal cord injury.

Spinal cord injury (SCI) elicits chronic pain in 65% of individuals. In addition, SCI afflicts an increasing number of aged individuals, and those with SCI are predisposed to shorter lifespan. Our group previously identified that deletion of the microRNA miR-155 reduced neuroinflammation and locomotor deficits after SCI.

Light at night during development in mice has modest effects on adulthood behavior and neuroimmune activation.

Exposure to light at night (LAN) can disrupt the circadian system, thereby altering neuroimmune reactivity and related behavior. Increased exposure to LAN affects people of all ages - and could have particularly detrimental effects during early-life and adolescence. Despite this, most research on the behavioral and physiological effects of LAN has been conducted in adult animals.

Alzheimer's Disease: Protective Effects of Mycobacterium vaccae, a Soil-Derived Mycobacterium with Anti-Inflammatory and Anti-Tubercular Properties, on the Proteomic Profiles of Plasma and Cerebrospinal Fluid in Rats.

Background: Alzheimer's disease (AD) is an inflammatory neurodegenerative disease that may be associated with prior bacterial infections. Microbial "old friends" can suppress exaggerated inflammation in response to disease-causing infections or increase clearance of pathogens such as Mycobacterium tuberculosis, which causes tuberculosis (TB). One such "old friend" is Mycobacterium vaccae NCTC 11659, a soil-derived bacterium that has been proposed either as a vaccine for prevention of TB, or as immunotherapy for the treatment of TB when used alongside first line anti-TB drug treatment.

Comparing the effects of two different strains of mycobacteria, Mycobacterium vaccae NCTC 11659 and M. vaccae ATCC 15483, on stress-resilient behaviors and lipid-immune signaling in rats.

Stress-related disorders, such as posttraumatic stress disorder (PTSD), are highly prevalent and often difficult to treat. In rodents, stress-related, anxiety-like defensive behavioral responses may be characterized by social avoidance, exacerbated inflammation, and altered metabolic states. We have previously shown that, in rodents, subcutaneous injections of a heat-killed preparation of the soil-derived bacterium Mycobacterium vaccae NCTC 11659 promotes stress resilience effects that are associated with immunoregulatory signaling in the periphery and the brain.

Dim light at night exacerbates stroke outcome.

Circadian rhythms are endogenous biological cycles that synchronize physiology and behaviour to promote optimal function. These ~24-hr internal rhythms are set to precisely 24 hr daily by exposure to the sun. However, the prevalence of night-time lighting has the potential to dysregulate these biological functions.

Acute stress induces chronic neuroinflammatory, microglial and behavioral priming: A role for potentiated NLRP3 inflammasome activation.

Prior exposure to acute and chronic stressors potentiates the neuroinflammatory and microglial pro-inflammatory response to subsequent immune challenges suggesting that stressors sensitize or prime microglia. Stress-induced priming of the NLRP3 inflammasome has been implicated in this priming phenomenon, however the duration/persistence of these effects has not been investigated. In the present study, we examined whether exposure to a single acute stressor (inescapable tailshock) induced a protracted priming of the NLRP3 inflammasome as well as the neuroinflammatory, behavioral and microglial proinflammatory response to a subsequent immune challenge in hippocampus.

The behavioral and neurochemical effects of an inescapable stressor are time of day dependent.

Circadian rhythms are ∼24 h fluctuations in physiology and behavior that are synchronized with the light-dark cycle. The circadian system ensures homeostatic balance by regulating multiple systems that respond to environmental stimuli including stress systems. In rats, acute exposure to a series of uncontrollable tailshocks (inescapable stress, IS) produces an anxiety and depression-like phenotype.

Circadian regulation of depression: A role for serotonin.

Synchronizing circadian (24 h) rhythms in physiology and behavior with the environmental light-dark cycle is critical for maintaining optimal health. Dysregulation of the circadian system increases susceptibility to numerous pathological conditions including major depressive disorder. Stress is a common etiological factor in the development of depression and the circadian system is highly interconnected to stress-sensitive neurotransmitter systems such as the serotonin (5-hydroxytryptamine, 5-HT) system.

Dim light at night impairs recovery from global cerebral ischemia.

Nighttime lighting is one of the great conveniences of modernization; however, there is mounting evidence that inopportune light exposure can disrupt physiological and behavioral functions. Hospital patients may be particularly vulnerable to the consequences of light at night due to their compromised physiological state. Cardiac arrest/cardiopulmonary resuscitation (CA) was used to test the hypothesis in mice that exposure to dim light at night impairs central nervous system (CNS) recovery from a major pathological insult.