Impact of GRIK4 gene polymorphisms on cognitive dysfunction in patients with major depression

Pu, Mengjia; Wang, X.; Zhang, J.

doi:10.1016/j.neurol.2019.11.009

Cited by 4 publications

(2 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the individual men contrast, the meta-analysis found overexpression in men.MS of the genes: COMMD9 (COMM Domain Containing 9, related to mental retardation syndrome and related to innate immune system); COX genes (COX6B1 and COX8A, two cytochrome oxidases involved in mitochondrial function); GLA (gene related to galactosidase metabolism); GRIK4 (a glutamate receptor ionotropic kainate 4 with a role in cognitive dysfunction and neurodegenerative diseases) [38]; PSMB2 (proteasome B-type family, whose dysregulation has been described in Parkinson’s disease) [39]; SOCS3 protein , (a suppressor of cytokine signaling); SRP14 (Signal Recognition Particle 14,whose related pathways are metabolism of proteins and innate immune system); TESC (Tescalcin, that include calcium ion binding and magnesium ion binding). This gene has been described as a potential target of class I histone deacetylase inhibitors in neurons with a neuroprotective effect [40]; TMX (transmembrane Trx-like protein 4, with reductase activity) [41]; TXNL4A, (subunit of a protein complex called the major spliceosome, related to craniofacial developmental disorder) [42]; UXT, (Ubiquitously Expressed Prefoldin Like Chaperone, that functions as a cofactor that modulates androgen receptor-dependent transcription), essential for cell viability and cell transformation.…”

Section: Resultsmentioning

confidence: 99%

A Deep Transcriptome Meta-Analysis Reveals Sex-based Molecular Differences in Multiple Sclerosis

Català-Senent

Andreu

Roig

et al. 2021

Preprint

View full text Add to dashboard Cite

Background: Multiple Sclerosis (MS) is a chronic autoimmune, inflammatory, and degenerative disease of the central nervous system that affects both women and men but the risk of developing MS is higher in women (2-3:1 ratio compared to men). Current knowledge does not allow a precise definition of the sex-related factors intervening in MS. Here, we explore the role of sex in this neurodenegerative disease to identify molecular mechanisms underlying sex-based diferences that can guide novel therapeutics approaches aimed for men and women. Methods: We performed a rigorous and systematic review of MS whole transcriptome studies that included sex patient information in Gene Expression Omnibus and ArrayExpress databases, following PRISMA statment guidelines. A differential gene expression (DGE) was performed for each selected study. Then, three meta-analyses based on genes and different contrasts were addressed to evaluate common features and sex bias in all scenarios: one meta-analysis in nervous tissue studies (4), another in blood studies (5), and a third that integrated the studies from both tissues, blood and nervous system (9). Finally, a gene set analysis (GSA) was performed on the meta-analyzed differential transcriptomic profile between women and men, to study their involvement in biological pathways and phenotypes (physiological and pathological states) sex related. Results: After screening 122 publications, the systematic review provided a selection of nine studies (5 in blood and 4 in nervous tissue) with a total of 653 samples (269 MS women, 152 control women, 116 MS men, 116 control men). The blood sex-differences gene meta-analysis identified 1 gene overexpressed in women (KIR2DL3) while gene meta-analysis in the nervous tissue resulted in 5 genes differentially expressed (4 overexpressed in women: C7orf73, CECR7, TRAF3IP2-AS1, ZNF117; and 1 overexpressed in men: HIST1H2AE). In the global meta-analysis (blood and nervous tissue), 1 gene involved in sex differences were detected (more expressed in women: LOC102723701). 9 MS biomarkers were also identified in both sexes (4 overexpressed genes in MS patients: HIST1H2BC, SMEK2, STBD1, TMEM140) and 5 down-regulated in MS patients: C16orf59, C20orf177, C9orf23, FAM65B, PKI55). Additionally, the GSA related to gene meta-analysis revealed a set of functions differentially enriched in men and women, in the different analysed tissues. Conclusion: These findings provide valuable opportunities for better understanding of MS related sex differences and develop effective and sex-specific interventions down further studies.

show abstract

Section: Resultsmentioning

confidence: 99%

A Deep Transcriptome Meta-Analysis Reveals Sex-based Molecular Differences in Multiple Sclerosis

Català-Senent

Andreu

Roig

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…In situ hybridisation and RNA sequencing studies in mice suggest that Grik4 mRNA is also expressed in the cerebellum (Falcon-Moya et al ., 2018), amygdala (Arora et al, 2018) and cortex (Arora et al ., 2018; Zhang et al ., 2014). Genetic variants identified in GRIK4 in humans have been associated with schizophrenia (Hu et al ., 2022), depression and its treatment (Minelli et al ., 2016; Pu et al ., 2020; Ren et al ., 2017), bipolar disorder (Koromina et al ., 2019), and autism (Griswold et al ., 2012). Methylation changes in GRIK4 also implicate GluK4-kainite receptor signalling with the progression of motor dysfunction in Huntington’s disease (Lu et al ., 2020).…”

Section: Introductionmentioning

confidence: 99%

Gluk4-containing kainate receptors regulate synaptic communication in the motor cortex and reduce axon degeneration in adult mice

Ricci,

Fletcher,

Makowiecki

et al. 2024

Preprint

View full text Add to dashboard Cite

Glutamate-gated kainate receptors comprising the Gluk4 subunit (encoded by Grik4) are highly expressed by neurons in the central nervous system. We report that Grik4 mRNA is widely expressed by neurons in the adult mouse motor cortex, where GluK4-containing kainate receptors account for ~60% of the kainate evoked current in layer V pyramidal neurons. To elucidate their role in motor circuit regulation, we analyzed the behavior of mice that lacked the pore forming domain of the GluK4 subunit (Grik4-/- mice). Grik4-/- mice were hyperactive, had an abnormal gait, and impaired motor coordination. At postnatal day (P)60, layer V pyramidal neurons received fewer miniature excitatory post synaptic currents, had a reduced density of thin spines on their basal dendrites, and a reduced density of VGlut1 puncta at the soma, consistent with neurons receiving fewer excitatory synaptic connections. Grik4-/- mice also lost ~44% of their callosal axons between P60 and P180 and the amplitude of the callosal compound action potential was reduced by ~25-30%. RNA sequencing data support the capacity for Grik4 to modulate synaptic and neuroprotective signaling pathways.

show abstract

Application of computerized cognitive test battery in major depressive disorder: a narrative literature review

Cao

Xiao

Chen

et al. 2021

Nordic Journal of Psychiatry

View full text Add to dashboard Cite

Impact of GRIK4 gene polymorphisms on cognitive dysfunction in patients with major depression

Cited by 4 publications

References 41 publications

A Deep Transcriptome Meta-Analysis Reveals Sex-based Molecular Differences in Multiple Sclerosis

A Deep Transcriptome Meta-Analysis Reveals Sex-based Molecular Differences in Multiple Sclerosis

Gluk4-containing kainate receptors regulate synaptic communication in the motor cortex and reduce axon degeneration in adult mice

Application of computerized cognitive test battery in major depressive disorder: a narrative literature review

Contact Info

Product

Resources

About