Behavioral and Synaptic Circuit Features in a Zebrafish Model of Fragile X Syndrome.
Behavioral and Synaptic Circuit Features in a Zebrafish Model of Fragile X Syndrome.
PLoS One. 2013; 8(3): e51456
Ng MC, Yang YL, Lu KT
Fragile X syndrome (FXS) is the most frequent inherited form of human mental retardation. It is characterized by cognitive impairment and physical and behavioral problems and is caused by the silencing of fmr1 transcription and the absence of the fmr1 protein (FMRP). Recently, animal models of FXS have greatly facilitated the investigation of the molecular and cellular mechanisms of this loss-of-function disorder. The present study was aimed to further characterize the role of FMRP in behavior and synaptic function by using fmr1 knockout zebrafish. In adult zebrafish, we found that fmr1 knockout produces the anxiolytic-like responses of increased exploratory behavior in light/dark and open-field tests and avoidance learning impairment. Furthermore, electrophysiological recordings from telencephalic slice preparations of knockout fish displayed markedly reduced long-term potentiation and enhanced long-term depression compared to wild-type fish; however, basal glutamatergic transmission and presynaptic function at the lateral (Dl) and medial (Dm) division of the dorsal telencephalon synapse remained normal. Taken together, our study not only evaluates the mechanism of FRMP but also suggests that zebrafish have valuable potential as a complementary vertebrate model in studying the molecular pathogenesis of human fragile X syndrome. HubMed – depression
Post-Natal Development of Synaptic Properties of the GABAergic Projection from Inferior Colliculus to Auditory Thalamus.
J Neurophysiol. 2013 Mar 27;
Venkataraman Y, Bartlett EL
Development of auditory temporal processing is important for processing complex sounds as well as for acquiring reading and language skills. Neuronal properties and sound processing change dramatically in auditory cortex neurons after the onset of hearing. However, development of the auditory thalamus or medial geniculate body (MGB) has not been well studied over this critical time window. Since synaptic inhibition has been shown to be crucial for auditory temporal processing, this study examined the development of a feedforward, GABAergic connection to the MGB from the inferior colliculus (IC), which is also the source of sensory glutamatergic inputs to the MGB. IC – MGB inhibition was studied using whole-cell patch clamp recordings from rat brain slices in current-clamp and voltage-clamp at three age groups; pre-hearing (postnatal days 7-9, or P7-9), immediately post-hearing (P15-17) and a juvenile group (P22-32) whose neuronal properties are largely mature. Membrane properties matured substantially across the ages studied. GABAA and GABAB IPSPs were present at all ages and similar in amplitude. IPSPs became faster to single shocks, shower less depression to train stimuli at 5 HZ and 10 Hz, and overall more efficacious in controlling excitability, with age. Overall, IC – MGB inhibition becomes faster and more precise during a time period of rapid changes across the auditory system due to co-development of membrane properties and synaptic properties. HubMed – depression
Depression, Obesity and Smoking were Independently Associated with Inadequate Glycemic Control in Patients with Type 1 Diabetes.
Eur J Endocrinol. 2013 Mar 27;
Melin EO, Thunander M, Svensson R, Landin-Olsson M, Thulesius HO
OBJECTIVE: The aim of this study was to explore the associations between inadequate glycemic control of diabetes and psychological, anthropometric and life style variables in a population based cohort of type 1 diabetes patients. DESIGN: Cross-sectional study. METHODS: In this study 292 patients with type 1 diabetes participated, age 18-59 years. Psychological data were assessed by self-report instruments, Hospital Anxiety and Depression Scale and Toronto Alexithymia Scale-20. Anthropometrics, blood analyses, data from medical records and data from the Swedish National Diabetes Registry were collected. RESULTS: Self-reported depression (Adjusted Odds Ratio (AOR) 4.8), obesity (AOR 4.3) and smoking (AOR 3.0) were independently associated with inadequate glycemic control of diabetes (HbA1c >8.6%). Gender stratified analyses showed that self-reported depression (AOR 19.8) and obesity (AOR 7.0) in women; and smoking in men (AOR 4.2) were associated with HbA1c >8.6%. Alexithymia, antidepressant medication and physical inactivity were associated with HbA1c >8.6% only in bivariate analyses. Alexithymia, self-rated anxiety, physical inactivity and absence of abdominal obesity were associated with self-reported depression. CONCLUSIONS: Depression was the only psychological factor independently associated with HbA1c >8.6%. The association was of comparable importance as obesity and smoking, well known risk factors for inadequate glycemic control and diabetes complications. The association between depression and HbA1c >8.6% was particularly strong for women. Alexithymia, which is a relatively stable personality trait, was associated with depression. In the future care of patients with diabetes, psychological aspects should be considered alongside anthropometrics and life style factors in order to achieve the goals for HbA1c. HubMed – depression
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