ABSTRACT
Attention deficit is one of the most prominent and disabling symptoms in Fragile X syndrome (FXS). Hypersensitivity to sensory stimuli contributes to attention difficulties by overwhelming and/or distracting affected individuals, which disrupts activities of daily living at home and learning at school. We find that auditory or visual distractors selectively impair visual discrimination performance in humans and mice with FXS but not in typically developing controls. In both species, males and females were examined. Vasoactive intestinal polypeptide (VIP) neurons were significantly modulated by incorrect responses in the poststimulus period during early distractor trials in WT mice, consistent with their known role as error signals. Strikingly, however, VIP cells from Fmr1 -/- mice showed little modulation in error trials, and this correlated with their poor performance on the distractor task. Thus, VIP interneurons and their reduced modulatory influence on pyramidal cells could be a potential therapeutic target for attentional difficulties in FXS.SIGNIFICANCE STATEMENT Sensory hypersensitivity, impulsivity, and persistent inattention are among the most consistent clinical features of FXS, all of which impede daily functioning and create barriers to learning. However, the neural mechanisms underlying sensory over-reactivity remain elusive. To overcome a significant challenge in translational FXS research we demonstrate a compelling alignment of sensory over-reactivity in both humans with FXS and Fmr1 -/- mice (the principal animal model of FXS) using a novel analogous distractor task. Two-photon microscopy in mice revealed that lack of modulation by VIP cells contributes to susceptibility to distractors. Implementing research efforts we describe here can help identify dysfunctional neural mechanisms associated not only with sensory issues but broader impairments, including those in learning and cognition.
Subject(s)
Fragile X Syndrome , Vasoactive Intestinal Peptide , Humans , Male , Female , Animals , Mice , Fragile X Mental Retardation Protein/genetics , Activities of Daily Living , Interneurons , Mice, Knockout , Disease Models, AnimalABSTRACT
Attention deficit is one of the most prominent and disabling symptoms in Fragile X Syndrome (FXS). Hypersensitivity to sensory stimuli contributes to attention difficulties by overwhelming and/or distracting affected individuals, which disrupts activities of daily living at home and learning at school. We find that auditory or visual distractors selectively impair visual discrimination performance in both humans and mice with FXS, but not their typically developing controls. Vasoactive intestinal polypeptide (VIP) neurons were significantly modulated by incorrect responses in the post-stimulus period during early distractor trials in WT mice, consistent with their known role as 'error' signals. Strikingly, however, VIP cells from Fmr1-/- mice showed little modulation in error trials, and this correlated with their poor performance on the distractor task. Thus, VIP interneurons and their reduced modulatory influence on pyramidal cells, could be a potential therapeutic target for attentional difficulties in FXS.
ABSTRACT
Introduction: There is sufficient evidence of the risks as-sociated with diabetes mellitus and cardiovascular diseasewith obesity. Occupational health continues to be a challengeto integrate the detection of metabolic risks and timely inter-ventions that prevent disability and deterioration of the qual-ity of life. Objective: To detect nutritional and metabolic risks in lab-oratory workers. Materials and methods: A descriptive and cross-sec-tional study was carried out in 26 workers (21 women and 5men) from a State Laboratory of Public Health of the State ofGuanajuato; Anthropometric indicators (weight, height, cir-cumference, percentage of body fat), biochemical indicators(glucose, cholesterol, LDL, HDL, triglycerides, creatinine andurea) were measured. Metabolic syndrome was analisys inthe participants. Results: The average age of the participants was 36.5 ±12 years; 50% of the women presented obesity and 76% apercentage of body fat higher than recommended. Mean glu-cose was 79±9 g/dL, cholesterol 176 ± 31 mg / dL, HDL12.9±49 mg/dL, LDL 23.9±97 mg/dL, triglycerides 152 ± 80mg / dL, Creatinine 0, 6±0.1 mg/dL and urea 25 ± 6.6 mg/dL. Metabolic syndrome were detected in five women. Conclusion: A cardiometabolic risk of 23.8% was found,mainly due to the presence of obesity, distribution, and per-centage of body fat in the workers, which with the averageage the early risk of type 2 diabetes mellitus, hypertensionand dyslipidemia.(AU)
