Genetic disruption of Grm5 causes complex alterations in motor activity, anxiety and social behaviors

Xu, Jian; Marshall, John; Kraniotis, Stephen; Nomura, Toshihiro; Zhu, Yongling; Contractor, Anis

doi:10.1016/j.bbr.2021.113378

Cited by 19 publications

(15 citation statements)

References 107 publications

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“…Of seven overlapping genes, Grm5 , encoding mGluR5, was the most highly ranked z score of seven DEPs ( z score = 12.8 and P = 0.008) and also displayed schizophrenia-associated up-regulation in the PsychENCODE brain RNA-seq dataset (log 2 FC = 0.043 and P = 0.02) ( 28 ). Moreover, mGluR5 was previously reported to be involved in the regulation of neural network activity and NMDAR function and plasticity ( 21 , 45 – 49 ). Therefore, Grm5 was of interest for follow-up functional analyses.…”

Section: Resultsmentioning

confidence: 99%

“…Inhibition of mGluR5 activity with MTEP in Mir501 -KO mice ameliorated sociability, memory, and sensorimotor gating deficits and normalized enhanced excitatory synaptic transmission induced by the loss of miR-501-3p. Previously, mGluR5 was reported to be associated with cognitive and social behaviors and conditioning of the sensorimotor gating process by enhancing NMDAR function ( 45 – 49 ). MTEP was also reported to normalize the group I mGluR-induced spontaneous glutamate release at a central auditory synapse ( 56 ).…”

Section: Discussionmentioning

confidence: 99%

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Loss of schizophrenia-related miR-501-3p in mice impairs sociability and memory by enhancing mGluR5-mediated glutamatergic transmission

et al. 2022

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Schizophrenia is a polygenetic disease, the heterogeneity of which is likely complicated by epigenetic modifications yet to be elucidated. Here, we performed transcriptomic analysis of peripheral blood RNA from monozygotic twins discordant for schizophrenia and identified a schizophrenia-associated down-regulated microRNA, miR-501-3p. We showed that the loss of miR-501-3p in germline knockout (KO) male mice resulted in dendritic structure defects, glutamatergic transmission enhancement, and sociability, memory, and sensorimotor gating disruptions, which were attenuated when miR-501 expression was conditionally restored in the nervous system. Combining the results of proteomic analyses with the known genes linked to schizophrenia revealed that metabotropic glutamate receptor 5 (mGluR5) was one of the miR-501-3p targets and was elevated in vivo upon loss of miR-501. Treatment with the mGluR5 negative allosteric modulator 3-2((-methyl-4-thiazolyl) ethynyl) pyridine or the N -methyl- d -aspartate receptor antagonist 2-amino-5-phosphonopentanoic acid ameliorated the deficits observed in Mir501 -KO mice. The epigenetic and pathophysiological mechanism that links miR-501-3p to the modulation of glutamatergic transmission provides etiological implications for schizophrenia.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Loss of schizophrenia-related miR-501-3p in mice impairs sociability and memory by enhancing mGluR5-mediated glutamatergic transmission

et al. 2022

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“…At the behavioral level, mGlu5 is involved in locomotor reactivity to novel environments, sensorimotor gating, anxiety, and cognition [ 257 ]. MGlu5 KO mice show alterations in the behavioral domains affected in ASD, such as burial behavior, social interaction, locomotor activity, and anxiety [ 258 ]. Accordingly, alterations in mGlu5 have been associated to diverse neurological and neuropsychiatric disorders, including FXS [ 220 , 259 ], attention-deficit/hyperactivity ADHD [ 260 ], ASD [ 155 ], schizophrenia [ 261 , 262 ] and epilepsy [ 32 ].…”

Section: Role Of Glutamatergic Transmission In Asd Pathophysiology: E...mentioning

confidence: 99%

Autism Spectrum Disorder: Focus on Glutamatergic Neurotransmission

Montanari

Martella

Bonsi

et al. 2022

IJMS

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Disturbances in the glutamatergic system have been increasingly documented in several neuropsychiatric disorders, including autism spectrum disorder (ASD). Glutamate-centered theories of ASD are based on evidence from patient samples and postmortem studies, as well as from studies documenting abnormalities in glutamatergic gene expression and metabolic pathways, including changes in the gut microbiota glutamate metabolism in patients with ASD. In addition, preclinical studies on animal models have demonstrated glutamatergic neurotransmission deficits and altered expression of glutamate synaptic proteins. At present, there are no approved glutamatergic drugs for ASD, but several ongoing clinical trials are currently focusing on evaluating in autistic patients glutamatergic pharmaceuticals already approved for other conditions. In this review, we provide an overview of the literature concerning the role of glutamatergic neurotransmission in the pathophysiology of ASD and as a potential target for novel treatments.

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“…The GRIK2 is highly expressed in the brain tissues of buffalo, goats, sheep, and cattle. Studies have reported that GRM5 is related to social interaction and sports behavior ( Xu et al, 2021 ). The swamp buffalo has a gentle temperament and is mainly used for servitude.…”

Section: Discussionmentioning

confidence: 99%

Analysis of genetic diversity and selection characteristics using the whole genome sequencing data of five buffaloes, including Xilin buffalo, in Guangxi, China

Chen

Zhu²,

Wu³

et al. 2023

Front. Genet.

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Buffalo is an economically important livestock that renders useful services to manhood in terms of meat, milk, leather, and draught. The Xilin buffalo is among the native buffalo breeds of China. In the present study, the genetic architecture and selection signature signals of Xilin buffalo have been explored. Correlation analysis of the population structure of Xilin buffalo was conducted by constructing NJ tree, PCA, ADMIXTURE and other methods. A total of twenty-five (n = 25) Xilin buffalo whole genome data and data of forty-six (n = 46) buffaloes published data were used. The population structure analysis showed that the Xilin buffalo belong to the Middle-Lower Yangtze. The genome diversity of Xilin buffalo was relatively high. The CLR, π ratio, FST, and XP-EHH were used to detect the candidate genes characteristics of positive selection in Xilin buffalo. Among the identified genes, most of the enriched signal pathways were related to the nervous system and metabolism. The mainly reported genes were related to the nervous system (GRM5, GRIK2, GRIA4), reproductive genes (CSNK1G2, KCNIP4), and lactation (TP63). The results of this study are of great significance for understanding the molecular basis of phenotypic variation of related traits of Xilin buffalo. We provide a comprehensive overview of sequence variations in Xilin buffalo genomes. Selection signatures were detected in genomic regions that are possibly related to economically important traits in Xilin buffalo and help in future breeding and conservation programs of this important livestock genetic resource.

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Genetic disruption of Grm5 causes complex alterations in motor activity, anxiety and social behaviors

Cited by 19 publications

References 107 publications

Loss of schizophrenia-related miR-501-3p in mice impairs sociability and memory by enhancing mGluR5-mediated glutamatergic transmission

Loss of schizophrenia-related miR-501-3p in mice impairs sociability and memory by enhancing mGluR5-mediated glutamatergic transmission

Autism Spectrum Disorder: Focus on Glutamatergic Neurotransmission

Analysis of genetic diversity and selection characteristics using the whole genome sequencing data of five buffaloes, including Xilin buffalo, in Guangxi, China

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