Excitatory/inhibitory imbalance in autism spectrum disorders: Implications for interventions and therapeutics.

نویسندگان

  • Genoveva Uzunova
  • Stefano Pallanti
  • Eric Hollander
چکیده

OBJECTIVES Imbalance between excitation and inhibition and increased excitatory-inhibitory (E-I) ratio is a common mechanism in autism spectrum disorders (ASD) that is responsible for the learning and memory, cognitive, sensory, motor deficits, and seizures occurring in these disorders. ASD are very heterogeneous and better understanding of E-I imbalance in brain will lead to better diagnosis and treatments. METHODS We perform a critical literature review of the causes and presentations of E-I imbalance in ASD. RESULTS E-I imbalance in ASD is due primarily to abnormal glutamatergic and GABAergic neurotransmission in key brain regions such as neocortex, hippocampus, amygdala, and cerebellum. Other causes are due to dysfunction of neuropeptides (oxytocin), synaptic proteins (neuroligins), and immune system molecules (cytokines). At the neuropathological level E-I imbalance in ASD is presented as a "minicolumnopathy". E-I imbalance alters the manner by which the brain processes information and regulates behaviour. New developments for investigating E-I imbalance such as optogenetics and transcranial magnetic stimulation (TMS) are presented. Non-invasive brain stimulation methods such as TMS for treatment of the core symptoms of ASD are discussed. CONCLUSIONS Understanding E-I imbalance has important implications for developing better pharmacological and behavioural treatments for ASD, including TMS, new drugs, biomarkers and patient stratification.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Selective Impact of MeCP2 and Associated Histone Deacetylases on the Dynamics of Evoked

25 An imbalance between the strengths of excitatory and inhibitory synaptic inputs has been 26 proposed as the cellular basis of autism and related neurodevelopmental disorders. Earlier studies 27 examining spontaneous levels of excitatory and inhibitory neurotransmission in forebrain regions 28 of Mecp2 mutant mice, models of the autism spectrum disorder Rett syndrome, have identified a 29 dec...

متن کامل

Unbalance between Excitation and Inhibition in Phenylketonuria, a Genetic Metabolic Disease Associated with Autism

Phenylketonuria (PKU) is the most common genetic metabolic disease with a well-documented association with autism spectrum disorders. It is characterized by the deficiency of the phenylalanine hydroxylase activity, causing plasmatic hyperphenylalaninemia and variable neurological and cognitive impairments. Among the potential pathophysiological mechanisms implicated in autism spectrum disorders...

متن کامل

Genetic Controls Balancing Excitatory and Inhibitory Synaptogenesis in Neurodevelopmental Disorder Models

Proper brain function requires stringent balance of excitatory and inhibitory synapse formation during neural circuit assembly. Mutation of genes that normally sculpt and maintain this balance results in severe dysfunction, causing neurodevelopmental disorders including autism, epilepsy and Rett syndrome. Such mutations may result in defective architectural structuring of synaptic connections, ...

متن کامل

Excitatory/Inhibitory Synaptic Imbalance Leads to Hippocampal Hyperexcitability in Mouse Models of Tuberous Sclerosis

Neural circuits are regulated by activity-dependent feedback systems that tightly control network excitability and which are thought to be crucial for proper brain development. Defects in the ability to establish and maintain network homeostasis may be central to the pathogenesis of neurodevelopmental disorders. Here, we examine the function of the tuberous sclerosis complex (TSC)-mTOR signalin...

متن کامل

Selective impact of MeCP2 and associated histone deacetylases on the dynamics of evoked excitatory neurotransmission.

An imbalance between the strengths of excitatory and inhibitory synaptic inputs has been proposed as the cellular basis of autism and related neurodevelopmental disorders. Previous studies examining spontaneous levels of excitatory and inhibitory neurotransmission in the forebrain regions of methyl-CpG-binding protein 2 (Mecp2) mutant mice, models of the autism spectrum disorder Rett syndrome, ...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:
  • The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry

دوره 17 3  شماره 

صفحات  -

تاریخ انتشار 2016