Mou K

References (2)

Title : Faster Gastrointestinal Transit, Reduced Small Intestinal Smooth Muscle Tone and Dysmotility in the Nlgn3(R451C) Mouse Model of Autism - Hosie_2024_Int.J.Mol.Sci_25_
Author(s) : Hosie S , Abo-Shaban T , Mou K , Balasuriya GK , Mohsenipour M , Alamoudi MU , Filippone RT , Belz GT , Franks AE , Bornstein JC , Nurgali K , Hill-Yardin EL
Ref : Int J Mol Sci , 25 : , 2024
Abstract : Individuals with autism often experience gastrointestinal issues but the cause is unknown. Many gene mutations that modify neuronal synapse function are associated with autism and therefore may impact the enteric nervous system that regulates gastrointestinal function. A missense mutation in the Nlgn3 gene encoding the cell adhesion protein Neuroligin-3 was identified in two brothers with autism who both experienced severe gastrointestinal dysfunction. Mice expressing this mutation (Nlgn3(R451C) mice) are a well-studied preclinical model of autism and show autism-relevant characteristics, including impaired social interaction and communication, as well as repetitive behaviour. We previously showed colonic dysmotility in response to GABAergic inhibition and increased myenteric neuronal numbers in the small intestine in Nlgn3(R451C) mice bred on a mixed genetic background. Here, we show that gut dysfunction is a persistent phenotype of the Nlgn3 R451C mutation in mice backcrossed onto a C57BL/6 background. We report that Nlgn3(R451C) mice show a 30.9% faster gastrointestinal transit (p = 0.0004) in vivo and have 6% longer small intestines (p = 0.04) compared to wild-types due to a reduction in smooth muscle tone. In Nlgn3(R451C) mice, we observed a decrease in resting jejunal diameter (proximal jejunum: 10.6% decrease, p = 0.02; mid: 9.8%, p = 0.04; distal: 11.5%, p = 0.009) and neurally regulated dysmotility as well as shorter durations of contractile complexes (mid: 25.6% reduction in duration, p = 0.009; distal: 30.5%, p = 0.004) in the ileum. In Nlgn3(R451C) mouse colons, short contractions were inhibited to a greater extent (57.2% by the GABA(A) antagonist, gabazine, compared to 40.6% in wild-type mice (p = 0.007). The inhibition of nitric oxide synthesis decreased the frequency of contractile complexes in the jejunum (WT p = 0.0006, Nlgn3(R451C) p = 0.002), but not the ileum, in both wild-type and Nlgn3(R451C) mice. These findings demonstrate that changes in enteric nervous system function contribute to gastrointestinal dysmotility in mice expressing the autism-associated R451C missense mutation in the Neuroligin-3 protein.
ESTHER : Hosie_2024_Int.J.Mol.Sci_25_
PubMedSearch : Hosie_2024_Int.J.Mol.Sci_25_
PubMedID: 38255906
Gene_locus related to this paper: mouse-3neur

Title : Alzheimer's Disease\; Mechanism, Mutations, and Applications of Nano-Medicine - Maisam_2023_Front.Biosci.(Landmark.Ed)_28_258
Author(s) : Maisam M , Khan MT , Lodhi MS , Mou K , Liu Z , Wei D
Ref : Front Biosci (Landmark Ed) , 28 :258 , 2023
Abstract : BACKGROUND: In the past 10 years, significant progress has been made in understanding the pathogenic chain of events that causes Alzheimer's disease (AD). According to the most widely accepted concept, the production and aggregation of beta-amyloid (Abeta) peptides play a critical role in AD. As a result, therapeutic intervention with these processes is the focus of intense research. The Abeta peptide is cleaved by the alpha-secretase, beta-secretase, and gamma-secretase enzymes in a region near the pathogenic amyloid precursor protein (APP) and mutations occurring site. METHODS: In the current review, a complete picture of the risk factors behind AD has been investigated. Mutations involved in AD progression have also been screened in various studies. RESULTS: Most of the mutations in the amyloid precursor protein (APP) can lead to the accumulation of APP oligomers in the brain, leading to AD. Several point mutations in APP can cause familial AD (FAD), including the Swedish mutation (K>M670/671N>L) and the A673>V mutation. The pathogenic A673>V mutation and Swedish mutation (M670>K/N671>L) are present in the same region of amyloid precursor protein (APP). However, the A673>T mutation has been shown to confer protection against AD. CONCLUSION: More investigations are needed from geographically distinct regions on mutations associated with AD development and applications of nanomedicines for better management of the disease burden in the future. Nanotechnology-produced metal nanoparticles (NPs) have gotten much attention because of their wide range of uses in the medicinal and agricultural industries. Nanomedicine containing potential phytochemicals, including GX-50 and curcumin conjugated with NPs, maybe a potential candidate for treating AD.
ESTHER : Maisam_2023_Front.Biosci.(Landmark.Ed)_28_258
PubMedSearch : Maisam_2023_Front.Biosci.(Landmark.Ed)_28_258
PubMedID: 37919079