title: Convergent evidence for mGluR5 in synaptic and neuroinflammatory pathways implicated in ASD.
abstract: The pathogenesis of Autism Spectrum Disorder (ASD), a serious neurodevelopmental disorder, is poorly understood. We review evidence for alterations in glutamatergic signalling in the aetiology of ASD, with a focus on the metabotropic glutamate receptor-5 (mGluR5). mGluR5 signalling is important for synapse formation, neuroplasticity and long term potentiation as well as neuroprotection and has been shown to have a regulatory role in neuroinflammation. Evidence for neuroinflammation in ASD is supported by increase in pro-inflammatory cytokines in the blood and cerebrospinal fluid (CSF) and increased number and activation of microglia in postmortem dorsolateral prefrontal cortex (DLPFC). mGlur5 signalling has also been shown to downregulate microglial activation. Therefore, we focus on mGluR5 as a potential unifying explanation for synapse alteration and neuroinflammation seen in ASD. Data from mGluR5 knockout mouse models, and syndromic and non syndromic forms of ASD are discussed in relation to how alterations in mGluR5 are associated with ASD symptoms. This review supports altered mGluR5 functioning as a convergent point in ASD pathogenesis and indicates more research is warranted into mGluR5 as a potential therapeutic target.
authors.affiliation: Department of Haematology, Austin Health, Heidelberg, VIC, Australia; Centre for Neural Engineering, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Daniela
authors.initials: D
authors.lastname: Zantomio
authors.affiliation: Centre for Neural Engineering, The University of Melbourne, Parkville, Victoria, Australia; Department of Psychiatry, The University of Melbourne, Parkville, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health, Australia.
authors.forename: Gursharan
authors.initials: G
authors.lastname: Chana
authors.affiliation: Centre for Neural Engineering, The University of Melbourne, Parkville, Victoria, Australia; Department of Psychiatry, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Liliana
authors.initials: L
authors.lastname: Laskaris
authors.affiliation: Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne & Melbourne Health, Parkville, Victoria, Australia; Department of Psychology, Monash University, Clayton, Vic, Australia.
authors.forename: Renee
authors.initials: R
authors.lastname: Testa
authors.affiliation: Department of Psychiatry, The University of Melbourne, Parkville, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health, Australia.
authors.forename: Ian
authors.initials: I
authors.lastname: Everall
authors.affiliation: Department of Psychiatry, The University of Melbourne, Parkville, Victoria, Australia; Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne & Melbourne Health, Parkville, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health, Australia.
authors.forename: Christos
authors.initials: C
authors.lastname: Pantelis
authors.affiliation: Centre for Neural Engineering, The University of Melbourne, Parkville, Victoria, Australia; Department of Psychiatry, The University of Melbourne, Parkville, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health, Australia; Centre for Integrative Brain Function, Australia. Electronic address: sskaf@unimelb.edu.au.
authors.forename: Efstratios
authors.initials: E
authors.lastname: Skafidas
mesh_terms: D000818:Animals; D001321:Autistic Disorder / Q000150:complications / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D001921:Brain / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004660:Encephalitis / Q000209:etiology / Q000473:pathology*; D006801:Humans; D051379:Mice; D017628:Microglia / Q000378:metabolism; D064529:Receptor, Metabotropic Glutamate 5 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D013569:Synapses / Q000378:metabolism*
chemical_list: D064529:Receptor, Metabotropic Glutamate 5
keywords: Autism spectrum disorder; GRM5; Glutamate; Microglia; Neurodevelopment; Neuroinflammation; mGluR5