Effects of Oral Administration of the Probiotic Lactobacillus rhamnosus GG on the Proteomic Profiles of Cerebrospinal Fluid and Immunoregulatory Signaling in the Hippocampus of Adult Male Rats.

Introduction: The microbiome-gut-brain axis, by modulating bidirectional immune, metabolic, and neural signaling pathways in the host, has emerged as a target for the prevention and treatment of psychiatric and neurological disorders. Oral administration of the probiotic bacterium Lactobacillus rhamnosus GG (LGG; ATCC 53103) exhibits anti-inflammatory effects, although the precise mechanisms by which LGG benefits host physiology and behavior are not known. The goal of this study was to explore the general effects of LGG on the cerebrospinal fluid (CSF) proteome and a biological signature of anti-inflammatory signaling in the central nervous system (CNS) of undisturbed, adult male rats.

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.

Effects of immunization with heat-killed Mycobacterium vaccae on autism spectrum disorder-like behavior and epileptogenesis in a rat model of comorbid autism and epilepsy.

Autism spectrum disorders (ASDs) and epilepsy are often comorbid. The basis for this co-occurrence remains unknown; however, inflammatory stressors during development are a shared risk factor. To explore this association, we tested the effect of repeated immunizations using a heat-killed preparation of the stress-protective immunoregulatory microbe Mycobacterium vaccae NCTC 11,659 (M.

Spinal Cord Injury in Rats Disrupts the Circadian System.

Spinal cord injury (SCI) perturbs many physiological systems. The circadian system helps maintain homeostasis throughout the body by synchronizing physiological and behavioral functions to predictable daily events. Whether disruption of these coordinated daily rhythms contributes to SCI-associated pathology remains understudied.

Mycobacterium vaccae immunization protects aged rats from surgery-elicited neuroinflammation and cognitive dysfunction.

Aging is a major risk factor for developing postoperative cognitive dysfunction. Neuroinflammatory processes, which can play a causal role in the etiology of postoperative cognitive dysfunction, are potentiated or primed as a function of aging. Here we explored whether exposure to a microorganism with immunoregulatory and anti-inflammatory properties, Mycobacterium vaccae NCTC 11659 (M.

Neuroinflammatory priming to stress is differentially regulated in male and female rats.

Exposure to stressors can enhance neuroinflammatory responses, and both stress and neuroinflammation are predisposing factors in the development of psychiatric disorders. Females suffer disproportionately more from several psychiatric disorders, yet stress-induced changes in neuroinflammation have primarily been studied in males. Here we tested whether exposure to inescapable tail shock sensitizes or 'primes' neuroinflammatory responses in male and female rats.

Stable, long-term, spatial memory in young and aged rats achieved with a one day Morris water maze training protocol.

Here, we present data demonstrating that a 1 d Morris water maze training protocol is effective at producing stable, long-term spatial memory in both young (3 mo old) and aged (24 mo old) F344xBN rats. Four trials in each of four sessions separated by a 2.5 h ISI produced robust selective search for the platform 1 and 4 d after training, in both age groups.

Glucocorticoids Mediate Short-Term High-Fat Diet Induction of Neuroinflammatory Priming, the NLRP3 Inflammasome, and the Danger Signal HMGB1.

The impact of the foods we eat on metabolism and cardiac physiology has been studied for decades, yet less is known about the effects of foods on the CNS, or the behavioral manifestations that may result from these effects. Previous studies have shown that long-term consumption of high-fat foods leading to diet-induced obesity sensitizes the inflammatory response of the brain to subsequent challenging stimuli, causing deficits in the formation of long-term memories. The new findings reported here demonstrate that short-term consumption of a high-fat diet (HFD) produces the same outcomes, thus allowing the examination of mechanisms involved in this process long before obesity and associated comorbidities occur.

The Alarmin HMGB1 Mediates Age-Induced Neuroinflammatory Priming.

Unlabelled: Amplified neuroinflammatory responses following an immune challenge occur with normal aging and can elicit or exacerbate neuropathology. The mechanisms mediating this sensitized or "primed" immune response in the aged brain are not fully understood. The alarmin high mobility group box 1 (HMGB1) can be released under chronic pathological conditions and initiate inflammatory cascades.

Insulin improves memory and reduces chronic neuroinflammation in the hippocampus of young but not aged brains.

The role of insulin in the brain is still not completely understood. In the periphery, insulin can decrease inflammation induced by lipopolysaccharide (LPS); however, whether insulin can reduce inflammation within the brain is unknown. Experiments administrating intranasal insulin to young and aged adults have shown that insulin improves memory.

Calcium dysregulation via L-type voltage-dependent calcium channels and ryanodine receptors underlies memory deficits and synaptic dysfunction during chronic neuroinflammation.

Background: Chronic neuroinflammation and calcium (Ca(+2)) dysregulation are both components of Alzheimer's disease. Prolonged neuroinflammation produces elevation of pro-inflammatory cytokines and reactive oxygen species which can alter neuronal Ca(+2) homeostasis via L-type voltage-dependent Ca(+2) channels (L-VDCCs) and ryanodine receptors (RyRs). Chronic neuroinflammation also leads to deficits in spatial memory, which may be related to Ca(+2) dysregulation.

Differential neuroprotective and anti-inflammatory effects of L-type voltage dependent calcium channel and ryanodine receptor antagonists in the substantia nigra and locus coeruleus.

Neuroinflammation and degeneration of catecholaminergic brainstem nuclei occur early in neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. Neuroinflammation increases levels of pro-inflammatory cytokines and reactive oxygen species which can alter neuronal calcium (Ca(+2)) homoeostasis via L-type voltage dependent calcium channels (L-VDCCs) and ryanodine receptors (RyRs). Alterations in Ca(+2) channel activity in the SN and LC can lead to disruption of normal pacemaking activity in these areas, contributing to behavioral deficits.