Matta SM

References (2)

Title : The Emerging Role of the Gut-Brain-Microbiota Axis in Neurodevelopmental Disorders - Hosie_2022_Adv.Exp.Med.Biol_1383_141
Author(s) : Hosie S , Abo-Shaban T , Lee CYQ , Matta SM , Shindler A , Gore R , Sharna SS , Herath M , Crack PJ , Franks AE , Hill-Yardin EL
Ref : Advances in Experimental Medicine & Biology , 1383 :141 , 2022
Abstract : Autism spectrum disorder (ASD; autism) is a prevalent neurodevelopmental disorder associated with changes in gut-brain axis communication. Gastrointestinal (GI) symptoms are experienced by a large proportion of individuals diagnosed with autism. Several mutations associated with autism modify cellular communication via neuronal synapses. It has been suggested that modifications to the enteric nervous system, an intrinsic nervous system of the GI tract, could contribute to GI dysfunction. Changes in gut motility, permeability, and the mucosal barrier as well as shifts in the large population of microbes inhabiting the GI tract could contribute to GI symptoms. Preclinical research has demonstrated that mice expressing the well-studied R451C missense mutation in Nlgn3 gene, which encodes cell adhesion protein neuroligin-3 at neuronal synapses, exhibit GI dysfunction. Specifically, NL3(R451C) mice show altered colonic motility and faster small intestinal transit. As well as dysmotility, macrophages located within the gut-associated lymphoid tissue of the NL3(R451C) mouse caecum show altered morphology, suggesting that neuro-inflammation pathways are modified in this model. Interestingly, NL3(R451C) mice maintained in a shared environment demonstrate fecal microbial dysbiosis indicating a role for the nervous system in regulating gut microbial populations. To better understand host-microbe interactions, further clarification and comparison of clinical and animal model profiles of dysbiosis should be obtained, which in turn will provide better insights into the efforts taken to design personalized microbial therapies. In addition to changes in neurophysiological measures, the mucosal component of the GI barrier may contribute to GI dysfunction more broadly in individuals diagnosed with a wide range of neurological disorders. As the study of GI dysfunction advances to encompass multiple components of the gut-brain-microbiota axis, findings will help understand future directions such as microbiome engineering and optimisation of the mucosal barrier for health.
ESTHER : Hosie_2022_Adv.Exp.Med.Biol_1383_141
PubMedSearch : Hosie_2022_Adv.Exp.Med.Biol_1383_141
PubMedID: 36587154
Gene_locus related to this paper: human-NLGN3

Title : An altered glial phenotype in the NL3(R451C) mouse model of autism - Matta_2020_Sci.Rep_10_14492
Author(s) : Matta SM , Moore Z , Walker FR , Hill-Yardin EL , Crack PJ
Ref : Sci Rep , 10 :14492 , 2020
Abstract : Autism Spectrum Disorder (ASD; autism) is a neurodevelopmental disorder characterised by deficits in social communication, and restricted and/or repetitive behaviours. While the precise pathophysiologies are unclear, increasing evidence supports a role for dysregulated neuroinflammation in the brain with potential effects on synapse function. Here, we studied characteristics of microglia and astrocytes in the Neuroligin-3 (NL3(R451C)) mouse model of autism since these cell types are involved in regulating both immune and synapse function. We observed increased microglial density in the dentate gyrus (DG) of NL3(R451C) mice without morphological differences. In contrast, WT and NL3(R451C) mice had similar astrocyte density but astrocyte branch length, the number of branch points, as well as cell radius and area were reduced in the DG of NL3(R451C) mice. Because retraction of astrocytic processes has been linked to altered synaptic transmission and dendrite formation, we assessed for regional changes in pre- and postsynaptic protein expression in the cortex, striatum and cerebellum in NL3(R451C) mice. NL3(R451C) mice showed increased striatal postsynaptic density 95 (PSD-95) protein levels and decreased cortical expression of synaptosomal-associated protein 25 (SNAP-25). These changes could contribute to dysregulated neurotransmission and cognition deficits previously reported in these mice.
ESTHER : Matta_2020_Sci.Rep_10_14492
PubMedSearch : Matta_2020_Sci.Rep_10_14492
PubMedID: 32879325