ABSTRACT
Intestinal microbiota are essential for healthy gastrointestinal function and also broadly influence brain function and behavior, in part, through changes in immune function. Gastrointestinal disorders are highly comorbid with psychiatric disorders, although biological mechanisms linking these disorders are poorly understood. The present study utilized rats bred for distinct emotional behavior phenotypes to examine relationships between emotionality, the microbiome, and immune markers. Prior work showed that Low Novelty Responder (LR) rats exhibit high levels of anxiety- and depression-related behaviors as well as myriad neurobiological differences compared to High Novelty Responders (HRs). Here, we hypothesized that the divergent HR/LR phenotypes are accompanied by changes in fecal microbiome composition. We used next-generation sequencing to assess the HR/LR microbiomes and then treated adult HR/LR males with an antibiotic cocktail to test whether it altered behavior. Given known connections between the microbiome and immune system, we also analyzed circulating cytokines and metabolic factors to determine relationships between peripheral immune markers, gut microbiome components, and behavioral measures. There were no baseline HR/LR microbiome differences, and antibiotic treatment disrupted the microbiome in both HR and LR rats. Antibiotic treatment exacerbated aspects of HR/LR behavior, increasing LRs' already high levels of anxiety-like behavior while reducing passive stress coping in both strains. Our results highlight the importance of an individual's phenotype to their response to antibiotics, contributing to the understanding of the complex interplay between gut microbes, immune function, and an individual's emotional phenotype.
Subject(s)
Exploratory Behavior , Microbiota , Animals , Anti-Bacterial Agents , Anxiety , Behavior, Animal , Emotions , Male , RatsABSTRACT
Selective serotonin reuptake inhibitor (SSRI) antidepressants are the mainstay treatment for the 10-20% of pregnant and postpartum women who suffer major depression, but the effects of SSRIs on their children's developing brain and later emotional health are poorly understood. SSRI use during pregnancy can elicit antidepressant withdrawal in newborns and increase toddlers' anxiety and social avoidance. In rodents, perinatal SSRI exposure increases adult depression- and anxiety-like behavior, although certain individuals are more vulnerable to these effects than others. Our study establishes a rodent model of individual differences in susceptibility to perinatal SSRI exposure, utilizing selectively bred Low Responder (bLR) and High Responder (bHR) rats that were previously bred for high versus low behavioral response to novelty. Pregnant bHR/bLR females were chronically treated with the SSRI paroxetine (10 mg/kg/day p.o.) to examine its effects on offspring's emotional behavior and gene expression in the developing brain. Paroxetine treatment had minimal effect on bHR/bLR dams' pregnancy outcomes or maternal behavior. We found that bLR offspring, naturally prone to an inhibited/anxious temperament, were susceptible to behavioral abnormalities associated with perinatal SSRI exposure (which exacerbated their Forced Swim Test immobility), while high risk-taking bHR offspring were resistant. Microarray studies revealed robust perinatal SSRI-induced gene expression changes in the developing bLR hippocampus and amygdala (postnatal days 7-21), including transcripts involved in neurogenesis, synaptic vesicle components, and energy metabolism. These results highlight the bLR/bHR model as a useful tool to explore the neurobiology of individual differences in susceptibility to perinatal SSRI exposure.
Subject(s)
Anxiety Disorders/physiopathology , Depressive Disorder/physiopathology , Paroxetine/toxicity , Prenatal Exposure Delayed Effects , Selective Serotonin Reuptake Inhibitors/toxicity , Amygdala/drug effects , Amygdala/growth & development , Amygdala/physiopathology , Animals , Animals, Newborn , Anxiety Disorders/drug therapy , Depressive Disorder/drug therapy , Disease Models, Animal , Exploratory Behavior/drug effects , Exploratory Behavior/physiology , Female , Gene Expression Regulation, Developmental/drug effects , Genetic Predisposition to Disease , Hippocampus/drug effects , Hippocampus/growth & development , Hippocampus/physiopathology , Male , Maternal Behavior/drug effects , Paroxetine/pharmacokinetics , Pregnancy , Rats, Sprague-Dawley , Selective Serotonin Reuptake Inhibitors/pharmacokineticsABSTRACT
A group of 162 maintenance patients, previously studied for compliance to suggested maintenance schedules, were surveyed for tooth loss over a 5-year period. The group was divided into those who complied to suggested maintenance schedules and those whose compliance was erratic. It was found that none of the patients who had complied to suggested maintenance schedules lost any teeth. In the erratic group, where all tooth loss occurred, it was found that the more often a patient presented for maintenance, the less likely he was to lose teeth. These findings are discussed in relation to current studies on efficacy of various therapies for periodontal diseases.
Subject(s)
Jaw, Edentulous, Partially/etiology , Patient Compliance , Periodontitis/prevention & control , Dental Scaling , Humans , Periodontitis/complications , Prognosis , Tooth Root/surgeryABSTRACT
The purpose of this study was to determine patient compliance with suggested maintenance schedules. All patients eligible for maintenance therapy in a private periodontal practice were included. The study covered a period of 8 years. All patients had chronic inflammatory periodontal disease and had been eligible for at least 1 year of maintenance therapy before the close of data collection. A total of 961 patients were studied; only 16% complied with recommended maintenance schedules. Erratic compliance was found in 49% of the patients and 34% never reported for any maintenance therapy.
