Genetics of glutamate and its receptors in autism spectrum disorder

Nisar, Sabah; Bhat, Ajaz A.; Masoodi, Tariq; Hashem, Sheema; Akhtar, Sabah; Ali, Taqdir; Amjad, Sara; Chawla, Sanjeev; Bagga, Puneet; Frenneaux, Michael; Reddy, Ravinder; Fakhro, Khalid; Haris, Mohammad

doi:10.1038/s41380-022-01506-w

Cited by 73 publications

(61 citation statements)

References 217 publications

(218 reference statements)

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“…Both increased and reduced mGlu5 functioning has been associated with ASD. In particular, dysregulation of mGlu5 signaling and thereby abnormal synaptic protein synthesis has been proposed as a critical factor besides abnormal mGlu5 receptor function due to interactions with its scaffolding proteins [ 128 , 129 , 130 ] ( Table 2 ).…”

Section: Prenatal Zinc-deficient Micementioning

confidence: 99%

Prenatal Zinc Deficient Mice as a Model for Autism Spectrum Disorders

Sauer

Hagmeyer

Grabrucker

2022

IJMS

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Epidemiological studies have shown a clear association between early life zinc deficiency and Autism Spectrum Disorders (ASD). In line with this, mouse models have revealed prenatal zinc deficiency as a profound risk factor for neurobiological and behavioral abnormalities in the offspring reminiscent of ASD behavior. From these studies, a complex pathology emerges, with alterations in the gastrointestinal and immune system and synaptic signaling in the brain, as a major consequence of prenatal zinc deficiency. The features represent a critical link in a causal chain that leads to various neuronal dysfunctions and behavioral phenotypes observed in prenatal zinc deficient (PZD) mice and probably other mouse models for ASD. Given that the complete phenotype of PZD mice may be key to understanding how non-genetic factors can modify the clinical features and severity of autistic patients and explain the observed heterogeneity, here, we summarize published data on PZD mice. We critically review the emerging evidence that prenatal zinc deficiency is at the core of several environmental risk factors associated with ASD, being mechanistically linked to ASD-associated genetic factors. In addition, we highlight future directions and outstanding questions, including potential symptomatic, disease-modifying, and preventive treatment strategies.

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Section: Prenatal Zinc-deficient Micementioning

confidence: 99%

Prenatal Zinc Deficient Mice as a Model for Autism Spectrum Disorders

Sauer

Hagmeyer

Grabrucker

2022

IJMS

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“…223 Previous findings have highlighted the importance of glutamate dysfunction in contributing to the aetiology of autism. [407][408][409][410][411] In addition to the above mentioned changes in glutamatergic neurons in ASD, the functional role of GABAergic inhibitory neurons is becoming increasingly clear. Neuropathological studies have provided evidence of reduced GABAR levels in the cortex and hippocampus, aberrant GAD1 and GAD2 mRNA expression in the postmortem cortex and cerebellum, and the interneuron markers parvalbumin (PV) and somatostatin (SST) are downregulated.…”

Section: Brain Regions and Neural Circuitsmentioning

confidence: 99%

Signalling pathways in autism spectrum disorder: mechanisms and therapeutic implications

Jiang

Lin

Long

et al. 2022

Sig Transduct Target Ther

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Autism spectrum disorder (ASD) is a prevalent and complex neurodevelopmental disorder which has strong genetic basis. Despite the rapidly rising incidence of autism, little is known about its aetiology, risk factors, and disease progression. There are currently neither validated biomarkers for diagnostic screening nor specific medication for autism. Over the last two decades, there have been remarkable advances in genetics, with hundreds of genes identified and validated as being associated with a high risk for autism. The convergence of neuroscience methods is becoming more widely recognized for its significance in elucidating the pathological mechanisms of autism. Efforts have been devoted to exploring the behavioural functions, key pathological mechanisms and potential treatments of autism. Here, as we highlight in this review, emerging evidence shows that signal transduction molecular events are involved in pathological processes such as transcription, translation, synaptic transmission, epigenetics and immunoinflammatory responses. This involvement has important implications for the discovery of precise molecular targets for autism. Moreover, we review recent insights into the mechanisms and clinical implications of signal transduction in autism from molecular, cellular, neural circuit, and neurobehavioural aspects. Finally, the challenges and future perspectives are discussed with regard to novel strategies predicated on the biological features of autism.

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“…High serum glutamic acid level in autistic children is helpful for the early diagnosis of ASD (Khalifa et al 2018).In almost all studies, plasma glutamic acid levels were higher in autism children than in controls. Impaired glutamatergic pathways are also potential therapeutic targets for ASD (Nisar et al 2022). Not only do autistic children have increased levels of glutamic acid in their plasma, but also their siblings and parents (Aldred et al 2003).Glutamic acid is an excitatory neurotransmitter that it is concentrated in the brain and usually has neuroprotective and cognitive functions.…”

Section: Amino Acidsmentioning

confidence: 99%

Intestinal Flora Composition and Exploration of New Therapeutic Methods in Children with Autism

Zhang¹,

Li²,

Chang³

2022

JMSR

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Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social communication impairments, narrow range of interests or activities, and repetitive behaviors. Early diagnosis and early intervention can achieve better prognostic effects. Many studies have shown that the occurrence and development of ASD is closely related to intestinal flora disorder, which leads to an extremely increased probability of gastrointestinal symptoms in autism children. In addition, intestinal flora disorder in early life may pose a certain threat for infants, including early colonization of microorganisms and early antibiotic administration. Meanwhile, intestinal flora disorder in autistic children also change short-chain fatty acids, amino acids, neurotransmitters in blood. This review focuses on the above points and the possible new methods for the treatment of ASD, expecting to provide new ideas for the treatment of autistic children in addition to behavioral intervention.

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Genetics of glutamate and its receptors in autism spectrum disorder

Cited by 73 publications

References 217 publications

Prenatal Zinc Deficient Mice as a Model for Autism Spectrum Disorders

Prenatal Zinc Deficient Mice as a Model for Autism Spectrum Disorders

Signalling pathways in autism spectrum disorder: mechanisms and therapeutic implications

Intestinal Flora Composition and Exploration of New Therapeutic Methods in Children with Autism

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