Understanding the roles of glutamine synthetase, glutaminase, and glutamate decarboxylase autoantibodies in imbalanced excitatory/inhibitory neurotransmission as etiological mechanisms of autism

Hamed, Najat; Al-Ayadhi, Laila; Osman, Mohamed A.; Elkhawad, Abdalla Omer; Qasem, Hanan; Al-Marshoud, Majida; Merghani, Nada M.; El‐Ansary, Afaf

doi:10.1111/pcn.12639

Cited by 18 publications

(13 citation statements)

References 83 publications

(95 reference statements)

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“…When analysed at the microscopical level, these animals displayed a suppressed glutamatergic synaptic transmission as a result of modified presynaptic release probability, with consequent changes in synaptic glutamate concentration and postsynaptic action potential coupling (Smith et al, 2011). Because of the role that astrocytes play in the maintenance of appropriate levels of glutamate in the synaptic cleft, the glutamine synthetase (GS), an enzyme expressed in astrocytes with a critical role in glutamate synthesis, has been examined and found to be increased in the blood plasma of autistic patients (Hamed et al, 2018). Furthermore, other astrocyte-specific proteins such as AQP4 and Cx43 are altered in postmortem brains of ASD patients, thereby suggesting an underlying abnormal astrocyte-neuron communication in the pathophysiology of ASD.…”

Section: Autism Spectrum Disordersmentioning

confidence: 99%

Astrocytic‐neuronal crosstalk gets jammed: Alternative perspectives on the onset of neuropsychiatric disorders

Roman

Egert

Benedetto

2020

Eur J of Neuroscience

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Among all glia cells, astrocytes represent a highly heterogeneous class of neural cells of neuroectodermal origin. They can be classified into two major groups: protoplasmic astrocytes, whose processes ensheath synapses and blood vessels in the grey matter, and fibrous astrocytes, which contact nodes of Ranvier and blood vessels in the white matter (for a review, see Tabata, 2015). The revolutionary realization that astrocytes are not only necessary for neuronal support, but

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Section: Autism Spectrum Disordersmentioning

confidence: 99%

Astrocytic‐neuronal crosstalk gets jammed: Alternative perspectives on the onset of neuropsychiatric disorders

Roman

Egert

Benedetto

2020

Eur J of Neuroscience

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“…GLS1 is the main glutamine metabolic enzyme in the brain rather than GLS2. High levels of GLSl protein were identified in many psychiatric and neurological diseases (Hamed et al., 2018 ; Huang et al., 2011 ). Microglial GLS1 deficiency could mitigate neuroinflammation in the lipopolysaccharide (LPS)‐induced depression model (Ji et al., 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Microglia activation in the mPFC mediates anxiety‐like behaviors caused by Staphylococcus aureus strain USA300

et al. 2022

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Introduction:Staphylococcus aureus (S. aureus) is considered as one of the major causative agents of serious hospital-and community-acquired infections. Recent studies have reported that S. aureus infection induced neuroinflammation and was linked with some mental disorders. To evaluate the effects of S. aureus infection on abnormal behaviors, we conducted the present study.Methods: A S. aureus USA300-infected mouse model was established using bacterial suspension injection into tail vein. A series of behavioral tests were performed after USA300 infection. The expression of cytokines was detected in serum and mPFC.The number and some morphological parameters of microglia were also evaluated by immunofluorescence staining.Results: Anxiety-like behaviors, instead of locomotor activity impairment or depression-like behaviors, were observed in mice infected with S. aureus USA300 compared with control. S. aureus USA300 infection caused overexpression of IL-6, TNF-α, and IL-1β in serum, resulted in microglial over-activation and excessive release of proinflammatory cytokines in the mPFC. In addition, overexpression of TLR2 accompanied by increased GLS1 and p-STAT3 was observed in the mPFC of mice infected with S. aureus USA300. Conclusion:This study provides evidence that S. aureus USA300 infection can lead to neuroinflammation in the mPFC of mice, which may contribute to the development of anxiety.

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“…39 Among the few previous studies on ASD and anti-GAD antibody, one showed 3/20 (15%) were positive while others reported all samples as seronegative. 36,[40][41][42] These studies did not include clinical assessment. To the best of our knowledge, this is the first report investigating anti-GAD in ASD comparing classical and regressive patterns.…”

Section: Discussionmentioning

confidence: 99%

Comparison of serum anti-neuronal antibody levels in patients having autism spectrum disorder with and without regression

et al. 2021

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Background. Autism Spectrum Disorders (ASD) may present with a delay in social and communication development, or less frequently, with regression in social and language skills. The reasons for this difference in clinical presentation are unknown, and the regressive symptoms in the second group suggest an acquired process. Methods. We investigated serum autoantibodies in these two types of ASD in a cross-sectional design in a total of 50 children, 24 with autistic regression and 26 with classical ASD according to the DSM-5 criteria. Clinical assessment by the Childhood Autism Rating Scale (CARS) and Ankara Developmental Screening Test (ADST), parental questionnaires consisting of the Aberrant Behavior Checklist (ABC) and Autism Behavior Checklist (AuBC) were completed. Serum samples were tested for anti-neuronal antibodies including anti-N-methyl-Daspartate receptor (NMDAR), anti-contactin-associated protein (CASPR2), anti-leucine rich glioma inactivated 1 (LG1), anti-glutamate type 2-amino-3-propionic Acid (AMPA) 1-2, anti-gamma amino butyric acid (GABA) B, anti-dipeptidyl aminopeptidase-like protein 6 (DPPX) and anti-glutamic acid decarboxylase 65(GAD). Results. Serum anti-GAD antibodies were at detectable levels in five (20.8%) patients with autistic regression, of whom three had 2 to 4-fold increased titers, and in none of the patients with classical ASD. The age of the father at the patient`s birth and the duration of autistic regression correlated with anti-GAD IgG levels (P: 0,045, P: 0.855 respectively) in the ASD-regression group. No other antibodies were detected in either group. Conclusions. Our results do not suggest a causative role of anti-neuronal antibodies, but the possibility of an autoimmune process accompanying regressive symptoms in a small subgroup of ASD.

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Understanding the roles of glutamine synthetase, glutaminase, and glutamate decarboxylase autoantibodies in imbalanced excitatory/inhibitory neurotransmission as etiological mechanisms of autism

Abstract: The obtained data indicate that GS and GLS1 are promising indicators of a neuronal excitation and inhibition system imbalance and that combined measured parameters are good predictive biomarkers of autism.

Cited by 18 publications

References 83 publications

Astrocytic‐neuronal crosstalk gets jammed: Alternative perspectives on the onset of neuropsychiatric disorders

Astrocytic‐neuronal crosstalk gets jammed: Alternative perspectives on the onset of neuropsychiatric disorders

Microglia activation in the mPFC mediates anxiety‐like behaviors caused by Staphylococcus aureus strain USA300

Comparison of serum anti-neuronal antibody levels in patients having autism spectrum disorder with and without regression

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