Pathophysiological dissociation of the interaction between time pressure and trait anxiety during spatial orientation judgments.

Spatial orientation is achieved by integrating visual, vestibular and proprioceptive cues. Individuals that rely strongly upon visual cues to facilitate spatial orientation are termed visually dependent. Heightened visual reliance commonly occurs in patients following vestibular dysfunction and can influence clinical outcome. Additionally, psychological factors, including anxiety, are associated with poorer clinical outcome following vestibular dysfunction. Given that visual dependency measures are affected by psychological and contextual influences, such as time pressure, we investigated the interaction between time pressure and anxiety upon visual dependency in healthy controls and vestibular migraine patients. Visual dependency was assessed using a "Rod and Disk" task at baseline and under time pressure (3 s to complete the task). Non-situational (trait) and situational (state) anxiety levels were quantified using the Spielberg State-Trait Anxiety Inventory. We calculated the change in visual dependency (VD) [∆VD = VDtime pressure  - VDbaseline ] and correlated it with participants' trait anxiety scores. We observed a significant negative correlation between trait anxiety and the change in VD (R2  = .393, p < .001) in healthy controls and a positive correlation in dizzy patients (R2  = .317, p < .001). That is, healthy individuals that were more anxious became less visually dependent under time pressure (i.e., more accurate), whereas less anxious individuals became more visually dependent. The reverse was observed in vestibular migraine patients. Our results illustrate that anxiety can differentially modulate task performance during spatial orientation judgements under time pressure in healthy individuals and dizzy patients. These findings have potential implications for individualised patient rehabilitation therapies.

Region-Specific Reduction of BDNF Protein and Transcripts in the Hippocampus of Juvenile Rats Prenatally Treated With Sodium Valproate.

Autism is a neurodevelopmental disorder characterized by a deep deficit in language and social interaction, accompanied by restricted, stereotyped and repetitive behaviors. The use of genetic autism animal models has revealed that the alteration of the mechanisms controlling the formation and maturation of neural circuits are points of convergence for the physiopathological pathways in several types of autism. Brain Derived Neurotrophic Factor (BDNF), a key multifunctional regulator of brain development, has been related to autism in several ways. However, its precise role is still elusive, in part, due to its extremely complex posttranscriptional regulation. In order to contribute to this topic, we treated prenatal rats with Valproate, a well-validated model of autism, to analyze BDNF levels in the hippocampus of juvenile rats. Valproate-treated rats exhibited an autism-like behavioral profile, characterized by a deficit in social interaction, anxiety-like behavior and repetitive behavior. In situ hybridization (ISH) experiments revealed that Valproate reduced BDNF mRNA, especially long-3'UTR-containing transcripts, in specific areas of the dentate gyrus (DG) and CA3 regions. At the same time, Valproate reduced BDNF immunoreactivity in the suprapyramidal and lucidum layers of CA3, but improved hippocampus-dependent spatial learning. The molecular changes reported here may help to explain the cognitive and behavioral signs of autism and reinforce BDNF as a potential molecular target for this neurodevelopmental disorder.

Prenatal valproate treatment produces autistic-like behavior and increases metabotropic glutamate receptor 1A-immunoreactivity in the hippocampus of juvenile rats.

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder characterized by deficits in social communication and social interaction, and repetitive and stereotypical patterns of behavior. Previously, a common physiopathological pathway, involving the control of synaptic protein synthesis, was proposed as a convergence point in ASD. In particular, a role for local mRNA translation activated by class I metabotropic glutamate receptor type 5 (mGluR5) was suggested in genetic syndromes with autistic signs and in the prenatal exposition to the valproate model of autism. However, the role of the other members of class I metabotropic glutamate receptors, including mGluR1, has been poorly studied. The present study analyzed the immunoreactivity for mGluR1a in the hippocampus of rats prenatally treated with valproate. Pregnant dams (embryonic day 12.5) were injected with valproate (450 mg/kg) and subsequently, the behavior and mGluR1a were evaluated at postnatal day 30. Experimental rats exhibited social deficit, repetitive conduct and anxious behaviors compared with that of the control animals. Additionally, the present study observed an increased level of mGluR1a-immunoreactivity in the hilus of dentate gyrus and in the CA1 alveus region of the hippocampus. These results suggested an over­functioning of mGluR1a signaling in the hippocampus, induced in the valproate model of autism, which may serve a role in cognitive and behavioral signs of ASD.