Neurotransmitter Systems in Autism Spectrum Disorder

Çetin, Fatih Hilmi; Tunca, Hüseyin; Güney, Esra; İşeri, Elvan

doi:10.5772/59122

Cited by 18 publications

(24 citation statements)

References 101 publications

(101 reference statements)

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“…6 Thus, alterations in free amino acid concentrations have important implications for brain function. 49,50 Lastly, we observed significant decreases in the concentration of the branched-chain amino acids (BCAAs) leucine and isoleucine, both of which serve as nitrogen donors for the production of the neurotransmitter glutamate. For example, serine, which is necessary for neuronal proliferation in the developing central nervous system, 4 was significantly decreased in the fetal brains of poly(I:C)-treated animals.…”

Section: Ta B L E 2 Concentrations Of Free Amino Acids In Fetal Brainsmentioning

confidence: 94%

“…47 Free amino acids in fetal brain contribute to protein and hormone synthesis, neurotransmission, neuromodulation, and energy production. GABA plays a key role in regulating cell migration and neuronal differentiation during fetal neurodevelopment, 49 and dysregulated GABAergic transmission has been implicated in both ASD and schizophrenia. Furthermore, many of the specific amino acids that were altered as a result of poly(I:C) play important roles in fetal brain development.…”

Section: Ta B L E 2 Concentrations Of Free Amino Acids In Fetal Brainsmentioning

confidence: 99%

“…48 Poly(I:C) also resulted in significantly decreased concentrations of the inhibitory neurotransmitters glycine and GABA as well as the excitatory neurotransmitter aspartic acid. GABA plays a key role in regulating cell migration and neuronal differentiation during fetal neurodevelopment, 49 and dysregulated GABAergic transmission has been implicated in both ASD and schizophrenia. 49,50 Lastly, we observed significant decreases in the concentration of the branched-chain amino acids (BCAAs) leucine and isoleucine, both of which serve as nitrogen donors for the production of the neurotransmitter glutamate.…”

Section: Ta B L E 2 Concentrations Of Free Amino Acids In Fetal Brainsmentioning

confidence: 99%

“…GABA plays a key role in regulating cell migration and neuronal differentiation during fetal neurodevelopment, 49 and dysregulated GABAergic transmission has been implicated in both ASD and schizophrenia. 49,50 Lastly, we observed significant decreases in the concentration of the branched-chain amino acids (BCAAs) leucine and isoleucine, both of which serve as nitrogen donors for the production of the neurotransmitter glutamate. 51 Previous studies have shown that decreased BCAA transport into the brain or increased BCAA catabolism within the brain is associated with ASD in both mice and humans.…”

Section: Ta B L E 2 Concentrations Of Free Amino Acids In Fetal Brainsmentioning

confidence: 99%

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Poly(I:C) alters placental and fetal brain amino acid transport in a rat model of maternal immune activation

McColl

Piquette‐Miller

2019

American J Rep Immunol

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Problem Maternal immune activation (MIA) during pregnancy is associated with increased chances of neurodevelopmental disorders including schizophrenia and autism spectrum disorder (ASD). However, the exact mechanism through which MIA contributes to altered neurodevelopment is unknown. Due to the important role that amino acids play in neurodevelopment, altered amino acid transport could play a role in neurodevelopmental disorders. Indeed, altered plasma concentrations of multiple amino acids have been reported in individuals with ASD or schizophrenia. Therefore, our objective was to determine whether virally mediated MIA induces changes in amino acid transporters in the placenta and fetal brain. Method of study Pregnant rats were administered poly(I:C) on gestational day 14, and placental and fetal tissues were collected 6, 24, and 48 hours later. Amino acid transporter expression was measured in the placenta and fetal brain using qPCR, Western blotting, and Simple Western. Free amino acid concentrations in the fetal brain were quantified using HPLC. Results Poly(I:C) increased mRNA expression of several amino acid transporters in the placenta and fetal brain over these timepoints. Conversely, poly(I:C) imposed significant decreases in the protein expression of ASCT1 and EAAT2 in placenta and expression of SNAT5, EAAT1, and GLYT1 in fetal brain. Functional consequences of altered transporter expression were demonstrated through widespread changes in the concentrations of free amino acids in the fetal brains. Conclusion Together, these results represent novel findings with the poly(I:C) MIA model and contribute to the understanding of how MIA during pregnancy potentially leads to neurodevelopmental disorders.

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Section: Ta B L E 2 Concentrations Of Free Amino Acids In Fetal Brainsmentioning

confidence: 94%

Section: Ta B L E 2 Concentrations Of Free Amino Acids In Fetal Brainsmentioning

confidence: 99%

Section: Ta B L E 2 Concentrations Of Free Amino Acids In Fetal Brainsmentioning

confidence: 99%

Section: Ta B L E 2 Concentrations Of Free Amino Acids In Fetal Brainsmentioning

confidence: 99%

See 2 more Smart Citations

Poly(I:C) alters placental and fetal brain amino acid transport in a rat model of maternal immune activation

McColl

Piquette‐Miller

2019

American J Rep Immunol

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“…One of such hypothesis is the neurotransmitter pathophysiology of Autism. Increasing number of literature have implicated elevated levels of neurotransmitters and related amino acids in autistic individuals compared to age and sex-matched controls 11,12,13,14,15 . This is often correlated with dysfunctional neuronal connectivity (hyper and hypo connectivity) in regions of the brain involved in cognitive and social functions 16,17,18,19 .Glutamate and Gamma Aminobutyric Acid (GABA) are the main excitatory and inhibitory neurotransmitters in the human brain and both have important roles during early development of the nervous system and during synapses 20 .…”

Section: Introductionmentioning

confidence: 99%

Neurotransmitter and amino acid levels in Nigerian children with autism spectrum disorders

Fagbayi¹,

Taiwo²,

Esezobor³

et al. 2019

Nig. J. Paed.

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Autism Spectrum Disorder (ASD), often referred to as Autism, is a clinically heterogeneous neurodevelopmental disorder with core-defining features of impaired socialization, impaired verbal and nonverbal communication, and restricted and repetitive patterns of behaviour. The disorder is presently diagnosed behaviourally, however the search for possible biomarkers that could aid earlier diagnosis have been on the increase. The present study aims to investigate plasma amino acid levels as a potential biomarker in ASD screening. Plasma levels of 20 amino acids (AA) (including neurotransmitters-GABA and glutamate) of autistic individuals and typical age and sex matched control, were determined using reversed-phase high performance liquid chromatography (RP-HPLC). All statistical analyses (independent t-test, spearman correlation, cohen's d effect size)were done using IBM SPSS version 20. A total of 31 plasma samples (18 Autism cases and 13 agesex matched controls) were analyzed with mean ages 8.44±4.87 for cases and 8.15±4.88 for controls. No significant intergroup difference was observed in the individual amino acid levels with the exception of glutamate (t = 5.472, df = 2.324, p = 0.000063), glutamine (t = 8.342, df = 14.780, p = 0.000001) , GABA (t = 6.601, df = 24.593, p = 0.000001), tryptophan (t = 3.568, df = 16.472, p = 0.002) and cysteine (t = 4.000, df = 13.762, p = 0.001).The amino acid profile and the glutamate -GABA levels can serve as biochemical markers for ASD, and can thus be utilized as screening for earlier diagnosis of the disorder.

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Gamma-Aminobutyric Acid Type A Receptor Variants are Associated with Autism Spectrum Disorders

et al. 2023

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Neurotransmitter Systems in Autism Spectrum Disorder

Cited by 18 publications

References 101 publications

Poly(I:C) alters placental and fetal brain amino acid transport in a rat model of maternal immune activation

Poly(I:C) alters placental and fetal brain amino acid transport in a rat model of maternal immune activation

Neurotransmitter and amino acid levels in Nigerian children with autism spectrum disorders

Gamma-Aminobutyric Acid Type A Receptor Variants are Associated with Autism Spectrum Disorders

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