Target For Autism Spectrum Disorder Research Articles

Nitric oxide: from systems biology to drug targets for autism spectrum disorder

Nitric oxide: from systems biology to drug targets for autism spectrum disorder

Memantine/Aripiprazole Combination Alleviates Cognitive Dysfunction in Valproic Acid Rat Model of Autism: Hippocampal CREB/BDNF Signaling and Glutamate Homeostasis

SummarySignificant efforts are increasingly directed towards identifying novel therapeutic targets for autism spectrum disorder (ASD) with a rising role of aberrant glutamatergic transmission in the pathogenesis of ASD-associated cellular and behavioral deficits. This study aimed at investigating the role of chronic memantine (20 mg/kg/day) and aripiprazole (3 mg/kg/day) combination therapy in the management of prenatal sodium valproate (VPA)-induced autistic-like/cognitive deficits in male Wistar rats. Pregnant female rats received a single intraperitoneal injection of VPA (600 mg/kg) to induce autistic-like behaviors in their offspring. Prenatal VPA induced autistic-like symptoms (decreased social interaction and the appearance of stereotyped behavior) with deficits in spatial learning (in Morris water maze) and cognitive flexibility (in the attentional set-shifting task) in addition to decreased hippocampal protein levels of phosphorylated cAMP response element-binding protein (p-CREB), brain-derived neurotrophic factor (BDNF), and gene expression of glutamate transporter-1 (Glt-1) with a decline in GABA/glutamate ratio (both measured by HPLC). These were accompanied by the appearance of numerous neurofibrillary tangles (NFTs) with enhanced apoptosis in hippocampal sections. Memantine/aripiprazole combination increased the protein levels of p-CREB, BDNF, and Glt-1 gene expression with restoration of GABA/glutamate balance, attenuation of VPA-induced neurodegenerative changes and autistic-like symptoms, and improvement of cognitive performance. This study draws attention to the favorable cognitive effects of memantine/aripiprazole combination in autistic subjects which could be mediated via enhancing CREB/BDNF signaling with increased expression of astrocytic Glt-1 and restoration of GABA/glutamate balance, leading to inhibition of hippocampal NFTs formation and neuronal apoptosis.

Cell Therapy Targets for Autism Spectrum Disorders: Hopes, Challenges and Future Directions.

Autism spectrum disorders as a group of pediatric neurodevelopmental diseases is a crucial part of the worldwide disabilities which have influence in communication skills, social interactions, and ability to understand the concepts. The precise pathophysiology of autism spectrum disorders due to the abundance of involved mechanisms is unknown. Some of these involved mechanisms are related to genetic factors, chronic neuro inflammation, mitochondrial dysfunction, oxidative stress, immune dysregulation, hormonal imbalance, and environmental factors. Current main treatments for autisms are behavioral, nutritional and medical therapies, however there is not definitive treatment approach. Therein, more novel therapies are still required to improve the symptoms. Several preclinical and clinical evidence were shown that stem cell therapy is a potential treatment option for autism spectrum disorders individuals. Considering the significant factors which can affect the outcome of stem cell therapeutic effects including stem cell types, route and dosage of administration, and mechanism of activity along with selecting best animal models can be very important in performing clinical trials.

Emotion regulation: A treatment target for autism spectrum disorder.

Individuals with autism spectrum disorder (ASD) tend to experience difficulties with emotion regulation (ER). Treatments designed to address ER difficulties in individuals with ASD are emerging. The authors review cognitive-behavioral therapy (CBT) and mindfulness-based treatments that have focused on ER difficulties in youth and young adults with ASD. In general, these treatments addressing ER skills have included awareness of emotions/psychoeducation about emotions, frustration tolerance, and ER skills, as well as practice and use of these skills during group therapy that sometimes includes caregivers. The results from these interventions are encouraging for individuals with high-functioning ASD because ER skills tend to improve following treatment. The inclusion of ER in other ASD treatments is discussed.

Microglia as possible therapeutic targets for autism spectrum disorders.

Malfunctions of the nervous and immune systems are now recognized to be fundamental causes of autism spectrum disorders (ASDs). Studies have suggested that the brain's resident immune cells, microglia are possible key players in ASDs. Specifically, deficits in synaptic pruning by microglia may underlie the pathogenesis of ASDs, in which excess synapses are occasionally reported. This idea has driven researchers to investigate causal links between microglial dysfunction and ASDs. In this review, we first introduce the characteristics of microglia in ASD brains and discuss their possible roles in the pathogenesis of ASDs. We also refer to immunomodulatory agents that could be potentially used as symptomatic therapies for ASDs in light of their ability to modify microglial functions. Finally, we will mention a possible strategy to radically cure some of the symptoms reported in ASDs through reorganizing neural circuits via microglia-dependent synaptic pruning.

Newer potential pharmacological targets for autism spectrum disorder.

Newer potential pharmacological targets for autism spectrum disorder.

New treatment targets for autism spectrum disorders: EU-AIMS

New treatment targets for autism spectrum disorders: EU-AIMS

Synapses as therapeutic targets for autism spectrum disorders: an international symposium held in pavia on july 4th, 2014.

New progresses into the molecular and cellular mechanisms of autism spectrum disorders (ASDs) have been discussed in 1 day international symposium held in Pavia (Italy) on July 4th, 2014 entitled “synapses as therapeutic targets for autism spectrum disorders” (satellite of the FENS Forum for Neuroscience, Milan, 2014). In particular, world experts in the field have highlighted how animal models of ASDs have greatly advanced our understanding of the molecular pathways involved in synaptic dysfunction leading sometimes to “synaptic clinical trials” in children.