The role of glutamate and its receptors in autism and the use of glutamate receptor antagonists in treatment

Rojas, Donald C.

doi:10.1007/s00702-014-1216-0

Cited by 171 publications

(115 citation statements)

References 155 publications

(174 reference statements)

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“…Based on data from human genetic studies and animal models, proteins that regulate glutamatergic synapse development or function are among the most robust candidates for ASD etiology (Rojas 2014). The early developmental time course of symptom emergence in ASD (from about six months to three years) coincides with a period of rapid synapse formation and maturation, followed by activitydependent synapse pruning and circuit refinement.…”

Section: Autism Spectrum Disordersmentioning

confidence: 99%

Glutamate Synapses in Human Cognitive Disorders

Volk

Chiu

Sharma

et al. 2015

Annu. Rev. Neurosci.

223

179

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Accumulating data, including those from large genetic association studies, indicate that alterations in glutamatergic synapse structure and function represent a common underlying pathology in many symptomatically distinct cognitive disorders. In this review, we discuss evidence from human genetic studies and data from animal models supporting a role for aberrant glutamatergic synapse function in the etiology of intellectual disability (ID), autism spectrum disorder (ASD), and schizophrenia (SCZ), neurodevelopmental disorders that comprise a significant proportion of human cognitive disease and exact a substantial financial and social burden. The varied manifestations of impaired perceptual processing, executive function, social interaction, communication, and/or intellectual ability in ID, ASD, and SCZ appear to emerge from altered neural microstructure, function, and/or wiring rather than gross changes in neuron number or morphology. Here, we review evidence that these disorders may share a common underlying neuropathy: altered excitatory synapse function. We focus on the most promising candidate genes affecting glutamatergic synapse function, highlighting the likely disease-relevant functional consequences of each. We first present a brief overview of glutamatergic synapses and then explore the genetic and phenotypic evidence for altered glutamate signaling in ID, ASD, and SCZ.

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Section: Autism Spectrum Disordersmentioning

confidence: 99%

Glutamate Synapses in Human Cognitive Disorders

Volk

Chiu

Sharma

et al. 2015

Annu. Rev. Neurosci.

223

179

View full text Add to dashboard Cite

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“…These are generally believed to represent neurodevelopmental abnormalities, although the pathological mechanisms are many, and they also can be widely different. The failure in synaptic wiring of the brain as well as aberrant neurotransmission are likely to be responsible for many types of autistic developments (Cellot and Cherubini, 2014; Giovedi et al ., 2014; Rojas, 2014); in addition, autistic pathology is often connected to oxidative stress (McGinnis, 2004; Smaga et al ., 2015). Astroglial function is critical for synaptogenesis, synaptic maturation and maintenance (Verkhratsky and Nedergaard, 2014); likewise, astroglial cells are the main source of ROS scavengers and anti-oxidants, such as glutathione and ascorbic acid, respectively (Bridges et al ., 2012; Wilson et al ., 2000).…”

Section: Neurodevelopmental Disordersmentioning

confidence: 99%

Translational potential of astrocytes in brain disorders

Verkhratsky

Steardo²,

Parpura

et al. 2016

Progress in Neurobiology

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Fundamentally, all brain disorders can be broadly defined as the homeostatic failure of this organ. As the brain is composed of many different cells types, including but not limited to neurons and glia, it is only logical that all the cell types/constituents could play a role in health and disease. Yet, for a long time the sole conceptualization of brain pathology was focused on the well-being of neurons. Here, we challenge this neuron-centric view and present neuroglia as a key element in neuropathology, a process that has a toll on astrocytes, which undergo complex morpho-functional changes that can in turn affect the course of the disorder. Such changes can be grossly identified as reactivity, atrophy with loss of function and pathological remodeling. We outline the pathogenic potential of astrocytes in variety of disorders, ranging from neurotrauma, infection, toxic damage, stroke, epilepsy, neurodevelopmental, neurodegenerative and psychiatric disorders, Alexander disease to neoplastic changes seen in gliomas. We hope that in near future we would witness glial-based translational medicine with generation of deliverables for the containment and cure of disorders. We point out that such as a task will require a holistic and multi-disciplinary approach that will take in consideration the concerted operation of all the cell types in the brain.

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“…Given the volume of literature, we will focus on studies of auditory processing and the resting-state, as there are several recent reviews that focus more broadly on the electrophysiology of autism. 17-19 …”

Section: Autism Spectrum Disorders (Asd)mentioning

confidence: 99%

Neuroimaging with magnetoencephalography: A dynamic view of brain pathophysiology

Wilson

Heinrichs‐Graham

Proskovec

et al. 2016

Translational Research

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Magnetoencephalography (MEG) is a noninvasive, silent, and totally-passive neurophysiological imaging method with excellent temporal resolution (∼1 ms) and good spatial precision (∼3-5 mm). In a typical experiment, MEG data are acquired while healthy controls and/or patients with neurologic or psychiatric disorders perform a specific cognitive task and/or receive sensory stimulation. The resulting data are generally analyzed using standard electrophysiological methods, coupled with advanced image reconstruction algorithms. To date, the total number of MEG instruments and associated users is significantly smaller than comparable human neuroimaging techniques, although this is likely to change in the near future with advances in the technology. Despite this small base, MEG research has made a significant impact on several areas of translational neuroscience, largely through its unique capacity to quantify the oscillatory dynamics of activated brain circuits in humans. This review focuses on the clinical areas where MEG imaging has arguably had the greatest impact, in regard to the identification of aberrant neural dynamics at the regional and/or network-level, monitoring of disease progression, determining how efficacious pharmacological and behavioral interventions modulate neural systems, and the development of neural markers of disease. Specifically, this review covers recent advances in understanding the abnormal neural oscillatory dynamics that underlie Parkinson's disease, autism spectrum disorders, HIV-associated neurocognitive disorders, cerebral palsy, attention-deficit/hyperactivity disorder, cognitive aging, and posttraumatic stress disorder. MEG imaging has had a major impact on how clinical neuroscientists understand the brain basis of these disorders, and its translational influence is rapidly expanding with new discoveries and applications emerging continuously.

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The role of glutamate and its receptors in autism and the use of glutamate receptor antagonists in treatment

Cited by 171 publications

References 155 publications

Glutamate Synapses in Human Cognitive Disorders

Glutamate Synapses in Human Cognitive Disorders

Translational potential of astrocytes in brain disorders

Neuroimaging with magnetoencephalography: A dynamic view of brain pathophysiology

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