RESUMO
Clinical studies indicate that obese individuals have an increased risk of developing co-morbid depressive illness and that these patients have reduced responses to antidepressant therapy, including selective serotonin reuptake inhibitors (SSRIs). Obesity, a condition of chronic mild inflammation including obesity-induced neuroinflammation, is proposed to contribute to decreases in synaptic concentrations of neurotransmitters like serotonin (5HT) by decreasing 5HT synthesis in the dorsal raphe nucleus (DRN) and/or affecting 5HT reuptake in DRN target regions like the hippocampus. In view of these observations, the goal of the current study was to examine inflammatory markers and serotonergic dynamics in co-morbid obesity and depression. Biochemical and behavioral assays revealed that high-fat diet produced an obesity and depressive-like phenotype in one cohort of rats and that these changes were marked by increases in key pro-inflammatory cytokines in the hippocampus. In real time using fast scan cyclic voltammetry (FSCV), we observed no changes in basal levels of hippocampal 5HT; however responses to escitalopram were significantly impaired in the hippocampus of obese rats compared to diet resistant rats and control rats. Further studies revealed that these neurochemical observations could be explained by increases in serotonin transporter (SERT) expression in the hippocampus driven by elevated neuroinflammation. Collectively, these results demonstrate that obesity-induced increases in neuroinflammation adversely affect SERT expression in the hippocampus of obese rats, thereby providing a potential synaptic mechanism for reduced SSRI responsiveness in obese subjects with co-morbid depressive illness.
Assuntos
Citalopram , Dieta Hiperlipídica , Animais , Citalopram/farmacologia , Hipocampo , Humanos , Obesidade/complicações , Ratos , Inibidores Seletivos de Recaptação de Serotonina/farmacologiaRESUMO
INTRODUCTION: Persons with Parkinson's disease (PwPD) suffer from motor and non-motor symptoms which significantly affect their quality of life (QoL), and the QoL of their care partners (CP). Tandem cycling reduces PwPD motor symptoms; however, no studies have examined other benefits or included PwPD CP. We conducted an 8-week community virtual reality (VR) tandem cycling intervention to assess the feasibility and efficacy for PwPD and their CP (i.e., PD dyads). We hypothesized that dyadic tandem cycling would improve (1) PwPD motor and non-motor symptoms and (2) dimensions of PD dyads' QoL and physiologic health. METHODS: Ten PD dyads were recruited to complete 8 weeks of progressive intensity, bi-weekly tandem cycling. At pre- and post-testing, PwPD were assessed using the Movement Disorder Society-Unified Parkinson's Disease Rating Scale-III (MDS-UPDRS-III), functional gait assessment (FGA), and 10-m gait speed test. PD dyads also completed emotional and cognitive status questionnaires [e.g., Geriatric Depression Scale-Short Form (GDS-SF)], and wore BodyGuard 2 heart rate (HR) monitors for 48 h to assess surrogate measures of heart rate variability. Statistical analyses were conducted using Student's t tests with significance set at p ≤ 0.05. RESULTS: Eight PD dyads and one PwPD completed the intervention. Retention of PwPD (90%) and CP (80%) was adequate, and PD dyad adherence ranged from 91.67 to 97.91%. PwPD demonstrated significant clinical improvements in MDS-UPDRS-III scores (- 7.38, p < 0.01), FGA scores (+ 3.50, p < 0.01), and 10-m gait speed times (+ 0.27 m/s, p < 0.01), in addition to significant self-reported improvements in mobility (- 13.61, p = 0.02), fatigue (- 5.99, p = 0.02), and social participation (+ 4.69, p < 0.01). CP depressive symptoms significantly decreased (- 0.88, p = 0.02), and PD dyads shared a significant increase in root mean square of the successive differences (RMSSD; p = 0.04). CONCLUSION: Our pilot study demonstrated feasibility and multiple areas of efficacy supporting further investigation of community VR tandem cycling as a therapeutic intervention for PD dyads.