Further mechanistic investigations by Tang et al. mTOR is a key regulator of synaptic protein synthesis 9, and aberrations in mTOR signaling have been linked to synaptic and neuroanatomical abnormalities 10, 11 that are associated with both syndromic (e.g., tuberous sclerosis 12, 13) and idiopathic ASD 14, 15, 16. Crucially, one such study 7 has suggested a link between postmortem dendritic synaptic surplus in ASD and hyperactivity of the mammalian target of rapamycin (mTOR) pathway 5. Postmortem histological examinations support this notion, as the presence of increased dendritic spine density in brain tissue of ASD patients has been repeatedly observed 6, 7, 8. These observations have led to the hypothesis that dysfunctional synaptic pruning and homeostasis might contribute to ASD pathology 3, 5. Despite the daunting phenotypic and etiologic complexity that characterizes ASD 2, multiple syndromic forms of ASD have been found to encompass mutations in genes that affect translational control, protein synthesis, and the structure, transmission, or plasticity of synapses 3, 4. Recent advances in neurogenetics have begun to shed light on the complex etiology of autism spectrum disorders (ASD) 1. Our findings causally link mTOR-related synaptic pathology to large-scale network aberrations, revealing a unifying multi-scale framework that mechanistically reconciles developmental synaptopathy and functional hyperconnectivity in autism. Finally, we show that the identified transcriptomic signature is predominantly expressed in a subset of children with autism, thereby defining a segregable autism subtype. Notably, we further demonstrate that children with idiopathic ASD exhibit analogous cortical-striatal hyperconnectivity, and document that this connectivity fingerprint is enriched for ASD-dysregulated genes interacting with mTOR or Tsc2. These deficits are completely rescued by pharmacological inhibition of mTOR. Using rsfMRI, electrophysiology and in silico modelling in Tsc2 haploinsufficient mice, we show that mTOR-dependent increased spine density is associated with ASD -like stereotypies and cortico-striatal hyperconnectivity.
These observations raise the question of whether excess of synapses causes aberrant functional connectivity in ASD. ASD is also characterized by atypical macroscale functional connectivity as measured with resting-state fMRI (rsfMRI).
Soyagam starion oil cause autism trial#
Silexan anxiety disorder clinical trial lavender oil pharmacology.Postmortem studies have revealed increased density of excitatory synapses in the brains of individuals with autism spectrum disorder (ASD), with a putative link to aberrant mTOR-dependent synaptic pruning. Silexan is a safe and effective treatment in anxiety disorders. Except for mild gastrointestinal symptoms, Silexan did not induce any adverse effects and did not cause drug interactions, sedation or withdrawal symptoms at daily doses of 80 or 160 mg. In addition, Silexan had beneficial effects on typical concomitant symptoms of anxiety disorders, such as impaired sleep, somatic complaints, co-morbid depression or decreased quality of life. HAM-A total score reductions between baseline and end of treatment were significantly superior to placebo in patients with subthreshold anxiety and comparable with those achieved under lorazepam or paroxetine in patients with GAD. In patients with subthreshold (subsyndromal) anxiety or generalised anxiety disorder (GAD), an anxiolytic effect of Silexan was evident after 2 weeks. Primary outcome measure was the HAM-A total score reduction, while single items were assessed with regard to effects on concomitant depressive symptoms and on quality of sleep. Here we review clinical trials investigating its anxiolytic efficacy, safety and tolerability in humans, as well as preclinical investigations supporting this therapeutic use.īesides three selected publications reporting preclinical investigations, seven clinical trials are included, of which five had a treatment duration of 6 or 10 weeks. Silexan is a lavender oil preparation available in 80-mg capsules.
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