GABAergic System Dysfunction in Autism Spectrum Disorders

Zhao, Haisheng; Mao, Xijing; Zhu, Cuilin; Zou, Xiaohan; Peng, Fanzhen; Yang, Wei; Li, Bingjin; Li, Guangquan; Ge, Tongtong; Cui, Ranji

doi:10.3389/fcell.2021.781327

Cited by 51 publications

(39 citation statements)

References 169 publications

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“…As the developmental depolarizing-to-hyperpolarizing switch in GABA transmission is critical for the correct establishment of the E/I balance [ 274 ], alterations in GABAergic signaling can impair normal cellular processing and cause deficits such as those observed in ASD [ 275 ]. To date, increasing evidence of dysfunction in the GABAergic neurotransmission system has been reported in patients and animal models of ASD [ 276 , 277 ]. In vivo 1H-MRS measurements have revealed a significant increase in plasma levels of GABA in children with ASD compared to controls [ 81 , 85 , 278 ].…”

Section: Gaba/glutamate Balance In Asdmentioning

confidence: 99%

Autism Spectrum Disorder: Focus on Glutamatergic Neurotransmission

Montanari

Martella

Bonsi

et al. 2022

IJMS

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Disturbances in the glutamatergic system have been increasingly documented in several neuropsychiatric disorders, including autism spectrum disorder (ASD). Glutamate-centered theories of ASD are based on evidence from patient samples and postmortem studies, as well as from studies documenting abnormalities in glutamatergic gene expression and metabolic pathways, including changes in the gut microbiota glutamate metabolism in patients with ASD. In addition, preclinical studies on animal models have demonstrated glutamatergic neurotransmission deficits and altered expression of glutamate synaptic proteins. At present, there are no approved glutamatergic drugs for ASD, but several ongoing clinical trials are currently focusing on evaluating in autistic patients glutamatergic pharmaceuticals already approved for other conditions. In this review, we provide an overview of the literature concerning the role of glutamatergic neurotransmission in the pathophysiology of ASD and as a potential target for novel treatments.

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Section: Gaba/glutamate Balance In Asdmentioning

confidence: 99%

Autism Spectrum Disorder: Focus on Glutamatergic Neurotransmission

Montanari

Martella

Bonsi

et al. 2022

IJMS

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“…Importantly, it was suggested that the dynamics of the visual rivalry is dependent on brain-wide excitatory-inhibitory balance -a process that is also proposed to be altered in autism, leading to the expression of core traits of ASD (reviewed in Zhao et al, 2022). Finally, our visual rivalry paradigm utilizes a bistable moving plaid, in which the subject's perception switches between the local motionbased, 'transparent' interpretation of the stimulus versus the global motion-based, 'coherent' interpretation.…”

Section: Introductionmentioning

confidence: 99%

Tug-of-peace: Visual Rivalry and Atypical Visual Motion Processing in MECP2 duplication Syndrome of Autism

Bogatova

Smirnakis

Palagina

2022

Preprint

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Extracting common patterns of neural circuit computations in autism spectrum and pinning them as a cause of specific core traits of autism is the first step towards identifying cell- and circuit-level targets for effective clinical intervention. Studies in human subjects with autism have identified functional links and common anatomical substrates between core restricted behavioral repertoire, cognitive rigidity, and over-stability of visual percepts during visual rivalry. To be able to study these processes with single-cell precision and exhaustive neuronal population coverage, we developed the visual bi-stable perception task for mice. Our task is based on plaid patterns consisting of two transparent gratings drifting at an angle of 120 degrees relative to each other. This results in spontaneous reversals of the perception between local component motion (motion of the plaid perceived as two separate moving grating components) and integrated global pattern motion (motion of the plaid perceived as a fused moving texture). This robust paradigm does not depend on the explicit report of the mouse, as the direction of the optokinetic nystagmus (OKN, rapid eye movements driven by either pattern or component motion) is used to infer the dominant percept. Using this paradigm, we found that the rate of perceptual reversals between global and local motion interpretations of the stimulus is reduced in MECP2 duplication mouse model of autism. Moreover, the stability of local motion percepts is greatly increased in MECP2 duplication mice at the expense of global motion percepts. Thus, our model reproduces a subclass of core features in human autism (reduced rate of visual rivalry and atypical perception of visual motion). This further offers a well-controlled approach for dissecting neuronal circuits underlying these core features if combined with mesoscale 2-photon imaging and optogenetic manipulation of neuronal circuits.

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“…Glutamate and GABA, functioning respectively as the primary excitatory [ 124 ] and inhibitory [ 125 ] neurometabolites in the central nervous system, play various key physiological roles (e.g., inflammation [ 126 ]), including the processing and modulation of pain [ 87 ]. Alterations in the metabolism of both molecules have been associated with chronic pain [ 88 ].…”

Section: Gut Microbiome Metabolites As Possible Contributors To Painmentioning

confidence: 99%

An unexpected connection: A narrative review of the associations between Gut Microbiome and Musculoskeletal Pain

Enrico

Methé

et al. 2022

Eur Spine J

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Purpose Multiple diverse factors contribute to musculoskeletal pain, a major cause of physical dysfunction and health-related costs worldwide. Rapidly growing evidence demonstrates that the gut microbiome has overarching influences on human health and the body’s homeostasis and resilience to internal and external perturbations. This broad role of the gut microbiome is potentially relevant and connected to musculoskeletal pain, though the literature on the topic is limited. Thus, the literature on the topic of musculoskeletal pain and gut microbiome was explored. Methods This narrative review explores the vast array of reported metabolites associated with inflammation and immune-metabolic response, which are known contributors to musculoskeletal pain. Moreover, it covers known modifiable (e.g., diet, lifestyle choices, exposure to prescription drugs, pollutants, and chemicals) and non-modifiable factors (e.g., gut architecture, genetics, age, birth history, and early feeding patterns) that are known to contribute to changes to the gut microbiome. Particular attention is devoted to modifiable factors, as the ultimate goal of researching this topic is to implement gut microbiome health interventions into clinical practice. Results Overall, numerous associations exist in the literature that could converge on the gut microbiome’s pivotal role in musculoskeletal health. Particularly, a variety of metabolites that are either directly produced or indirectly modulated by the gut microbiome have been highlighted. Conclusion The review highlights noticeable connections between the gut and musculoskeletal health, thus warranting future research to focus on the gut microbiome’s role in musculoskeletal conditions.

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GABAergic System Dysfunction in Autism Spectrum Disorders

Cited by 51 publications

References 169 publications

Autism Spectrum Disorder: Focus on Glutamatergic Neurotransmission

Autism Spectrum Disorder: Focus on Glutamatergic Neurotransmission

Tug-of-peace: Visual Rivalry and Atypical Visual Motion Processing in MECP2 duplication Syndrome of Autism

An unexpected connection: A narrative review of the associations between Gut Microbiome and Musculoskeletal Pain

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