Systems genetics analysis reveals the common genetic basis for pain sensitivity and cognitive function
Fuyi Xu,
Anran Chen,
Shuijing Pan
et al.
Abstract:BackgroundThere is growing evidence of a strong correlation between pain sensitivity and cognitive function under both physiological and pathological conditions. However, the detailed mechanisms remain largely unknown. In the current study, we sought to explore candidate genes and common molecular mechanisms underlying pain sensitivity and cognitive function with a transcriptome‐wide association study using recombinant inbred mice from the BXD family.MethodsThe pain sensitivity determined by Hargreaves' paw wi… Show more
“…In this study, we integrated phenotypic resources from the BXD panel, including more than 300 neural phenotypes from over 150 mouse strains. The recombinant inbred population of the BXD family, as one of the largest and well-characterized genetic reference populations, is the basis for studying various diseases, such as cancer, cognitive disorders, and heart diseases (Zhu et al, 2020 ; Bajpai et al, 2023 ; Zhou et al, 2023 ; Xu et al, 2024 ). The correlation of the BXD RI family has been extended to genetic analysis of behavioral phenotypes, including drug addiction, neurodegenerative processes, etc.…”
Section: Discussionmentioning
confidence: 99%
“…Thousands of transcriptomic/phenomic datasets have been published using these BXD strains over the past decades, consisting of ~250 phenotypes associated with cognitive function (Philip et al, 2010 ). In addition, since each BXD strain is a stable inbred, it can be replicated in large numbers, to facilitate the precise localization of complex traits with low to moderate heritability (Xu et al, 2024 ). The BXD panel showed a strong variation in methionine concentrations in the midbrain across different strains, suggesting that it is a suitable population for exploring potential mechanisms underlying the association between methionine and AD.…”
As a dietary strategy, methionine restriction has been reported to promote longevity and regulate metabolic disorders. However, the role and possible regulatory mechanisms underlying methionine in neurodegenerative diseases such as Alzheimer's disease (AD), remain unexplored. This study utilized the data from BXD recombinant inbred (RI) mice to establish a correlation between the AD phenotype in mice and methionine level. Gene enrichment analysis indicated that the genes associated with the concentration of methionine in the midbrain are involved in the dopaminergic synaptic signaling pathway. Protein interaction network analysis revealed that glycogen synthase kinase 3 beta (GSK-3β) was a key regulator of the dopaminergic synaptic pathway and its expression level was significantly correlated with the AD phenotype. Finally, in vitro experiments demonstrated that methionine deprivation could reduce the expression of Aβ and phosphorylated Tau, suggesting that lowering methionine levels in humans may be a preventive or therapeutic strategy for AD. In conclusion, our findings support that methionine is a high risk factor for AD. These findings predict potential regulatory network, theoretically supporting methionine restriction to prevent AD.
“…In this study, we integrated phenotypic resources from the BXD panel, including more than 300 neural phenotypes from over 150 mouse strains. The recombinant inbred population of the BXD family, as one of the largest and well-characterized genetic reference populations, is the basis for studying various diseases, such as cancer, cognitive disorders, and heart diseases (Zhu et al, 2020 ; Bajpai et al, 2023 ; Zhou et al, 2023 ; Xu et al, 2024 ). The correlation of the BXD RI family has been extended to genetic analysis of behavioral phenotypes, including drug addiction, neurodegenerative processes, etc.…”
Section: Discussionmentioning
confidence: 99%
“…Thousands of transcriptomic/phenomic datasets have been published using these BXD strains over the past decades, consisting of ~250 phenotypes associated with cognitive function (Philip et al, 2010 ). In addition, since each BXD strain is a stable inbred, it can be replicated in large numbers, to facilitate the precise localization of complex traits with low to moderate heritability (Xu et al, 2024 ). The BXD panel showed a strong variation in methionine concentrations in the midbrain across different strains, suggesting that it is a suitable population for exploring potential mechanisms underlying the association between methionine and AD.…”
As a dietary strategy, methionine restriction has been reported to promote longevity and regulate metabolic disorders. However, the role and possible regulatory mechanisms underlying methionine in neurodegenerative diseases such as Alzheimer's disease (AD), remain unexplored. This study utilized the data from BXD recombinant inbred (RI) mice to establish a correlation between the AD phenotype in mice and methionine level. Gene enrichment analysis indicated that the genes associated with the concentration of methionine in the midbrain are involved in the dopaminergic synaptic signaling pathway. Protein interaction network analysis revealed that glycogen synthase kinase 3 beta (GSK-3β) was a key regulator of the dopaminergic synaptic pathway and its expression level was significantly correlated with the AD phenotype. Finally, in vitro experiments demonstrated that methionine deprivation could reduce the expression of Aβ and phosphorylated Tau, suggesting that lowering methionine levels in humans may be a preventive or therapeutic strategy for AD. In conclusion, our findings support that methionine is a high risk factor for AD. These findings predict potential regulatory network, theoretically supporting methionine restriction to prevent AD.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.