Convergent evidence for mGluR5 in synaptic and neuroinflammatory pathways implicated in ASD

Zantomio, Daniela; Chana, Gursharan; Laskaris, Liliana; Testa, Renée; Everall, Ian; Pantelis, Christos; Skafidas, Efstratios

doi:10.1016/j.neubiorev.2015.02.006

Cited by 29 publications

(18 citation statements)

References 66 publications

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“…In recent years, investigations into the downstream effects of impaired FMRP expression have revealed deficits in mGluR-dependent long-term depression (LTD) and long-term potentiation (LTP), which are critical neuronal processes in learning [ 8 ]. Direct evidence from ASD animal studies has corroborated results from FXS studies, showing that mGluR5, in particular, is relevant to the pathogenesis of ASD (reviewed by Zantomio et al [ 104 ]). Other polymorphisms for glutamate receptors have been associated with ASD, such as polymorphisms in GluR6 [ 105 ].…”

Section: Glutamate Dysregulation In Psychiatric Disordersmentioning

confidence: 78%

Overview of Glutamatergic Dysregulation in Central Pathologies

2015

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As the major excitatory neurotransmitter in the mammalian central nervous system, glutamate plays a key role in many central pathologies, including gliomas, psychiatric, neurodevelopmental, and neurodegenerative disorders. Post-mortem and serological studies have implicated glutamatergic dysregulation in these pathologies, and pharmacological modulation of glutamate receptors and transporters has provided further validation for the involvement of glutamate. Furthermore, efforts from genetic, in vitro, and animal studies are actively elucidating the specific glutamatergic mechanisms that contribute to the aetiology of central pathologies. However, details regarding specific mechanisms remain sparse and progress in effectively modulating glutamate to alleviate symptoms or inhibit disease states has been relatively slow. In this report, we review what is currently known about glutamate signalling in central pathologies. We also discuss glutamate’s mediating role in comorbidities, specifically cancer-induced bone pain and depression.

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Section: Glutamate Dysregulation In Psychiatric Disordersmentioning

confidence: 78%

Overview of Glutamatergic Dysregulation in Central Pathologies

2015

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“…Immune aberrations consistent with dysregulated immune responses have been reported in autistic children, including skewed TH1/TH2 cytokine profiles [ 25 ], low natural killer (NK) cell activity [ 26 ] and an imbalance in serum immunoglobulin levels [ 27 ]. In addition, ASD has been linked to autoimmunity and chronic neuroinflammation caused by glutamatergic excitotoxicity and diminished GABAergic signals [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

Alterations in the MicroRNA of the Blood of Autism Spectrum Disorder Patients: Effects on Epigenetic Regulation and Potential Biomarkers

Vaccaro

Sorrentino

Salvador

et al. 2018

Behavioral Sciences

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Aims: Autism spectrum disorder (ASD) refers to a group of heterogeneous brain-based neurodevelopmental disorders with different levels of symptom severity. Given the challenges, the clinical diagnosis of ASD is based on information gained from interviews with patients’ parents. The heterogeneous pathogenesis of this disorder appears to be driven by genetic and environmental interactions, which also plays a vital role in predisposing individuals to ASD with different commitment levels. In recent years, it has been proposed that epigenetic modifications directly contribute to the pathogenesis of several neurodevelopmental disorders, such as ASD. The microRNAs (miRNAs) comprises a species of short noncoding RNA that regulate gene expression post-transcriptionally and have an essential functional role in the brain, particularly in neuronal plasticity and neuronal development, and could be involved in ASD pathophysiology. The aim of this study is to evaluate the expression of blood miRNA in correlation with clinical findings in patients with ASD, and to find possible biomarkers for the disorder. Results: From a total of 26 miRNA studied, seven were significantly altered in ASD patients, when compared to the control group: miR34c-5p, miR92a-2-5p, miR-145-5p and miR199a-5p were up-regulated and miR27a-3p, miR19-b-1-5p and miR193a-5p were down-regulated in ASD patients. Discussion: The main targets of these miRNAs are involved in immunological developmental, immune response and protein synthesis at transcriptional and translational levels. The up-regulation of both miR-199a-5p and miR92a-2a and down-regulation of miR-193a and miR-27a was observed in AD patients, and may in turn affect the SIRT1, HDAC2, and PI3K/Akt-TSC:mTOR signaling pathways. Furthermore, MeCP2 is a target of miR-199a-5p, and is involved in Rett Syndrome (RTT), which possibly explains the autistic phenotype in male patients with this syndrome.

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“…MICEST is sensitive to myoinositol, a glial cell marker that can be used as an indicator for neuroinflammatory response. Neuroinflammatory microglia activity has been reported in autism (126,127), mood disorders (128), and schizophrenia (129). Gene expression studies in postmortem brain tissue have also indicated glial abnormalities, including reduced expression of astrocyte related genes in the cerebral cortex of individuals with major depression (128) and oligodendrocyte related transcripts in bipolar disorder (130).…”

Section: Neuroinflammationmentioning

confidence: 99%

Proton Exchange Magnetic Resonance Imaging: Current and Future Applications in Psychiatric Research

et al. 2020

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Proton exchange provides a powerful contrast mechanism for magnetic resonance imaging (MRI). MRI techniques sensitive to proton exchange provide new opportunities to map, with high spatial and temporal resolution, compounds important for brain metabolism and function. Two such techniques, chemical exchange saturation transfer (CEST) and T1 relaxation in the rotating frame (T1r), are emerging as promising tools in the study of neurological and psychiatric illnesses to study brain metabolism. This review describes proton exchange for non-experts, highlights the current status of protonexchange MRI, and presents advantages and drawbacks of these techniques compared to more traditional methods of imaging brain metabolism, including positron emission tomography (PET) and MR spectroscopy (MRS). Finally, this review highlights new frontiers for the use of CEST and T1r in brain research.

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Convergent evidence for mGluR5 in synaptic and neuroinflammatory pathways implicated in ASD

Cited by 29 publications

References 66 publications

Overview of Glutamatergic Dysregulation in Central Pathologies

Overview of Glutamatergic Dysregulation in Central Pathologies

Alterations in the MicroRNA of the Blood of Autism Spectrum Disorder Patients: Effects on Epigenetic Regulation and Potential Biomarkers

Proton Exchange Magnetic Resonance Imaging: Current and Future Applications in Psychiatric Research

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