Tyrosine receptor kinase B gene variants (NTRK2 variants) are associated with depressive disorders in temporal lobe epilepsy

Torres, Carolina Machado; Siebert, Marina; Bock, Hugo; Mota, Suelen Mandelli; Castan, Juliana Unis; Scornavacca, Francisco; Castro, Luiza Amaral de; Saraiva-Pereira, Maria Luiza; Bianchin, Marino Muxfeldt

doi:10.1016/j.yebeh.2017.03.030

Cited by 12 publications

(7 citation statements)

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“…The phosphorylation of the IκB protein is a vital step in the activation of NF-κB and is regulated by IκB kinase (IKKs). The IKK activity is also induced by activators of the NF-κB pathways [46,47]. In the present study, we observed that aurantio-obtusin suppressed the activation of IKK-α and IKK-β; this underlies its inhibitory activity on NF-κB activation.…”

Section: Discussionsupporting

confidence: 64%

Anti-Inflammatory Effects of Aurantio-Obtusin from Seed of Cassia obtusifolia L. through Modulation of the NF-κB Pathway

Hou

Zhao

et al. 2018

Molecules

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Aurantio-obtusin, an anthraquinone compound, isolated from dried seeds of Cassia obtusifolia L. (syn. Senna obtusifolia; Fabaceae) and Cassia tora L. (syn. Senna tora). Although the biological activities of Semen Cassiae have been reported, the anti-inflammatory mechanism of aurantio-obtusin, its main compound, on RAW264.7 cells, remained unknown. We investigated the anti-inflammatory effect of aurantio-obtusin on lipopolysaccharide- (LPS)-induced RAW264.7 cells in vitro and elucidated the possible underlying molecular mechanisms. Nitric oxide production (NO) and prostaglandin E2 (PGE2) were measured by the Griess colorimetric method and enzyme-linked immunosorbent assay (ELISA), respectively. Protein expression levels of cyclooxygenase 2 (COX-2) were monitored by cell-based ELISA. Interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-α) synthesis were analyzed using ELISA. The mRNA expression of nitric oxide synthase (iNOS), COX-2, and the critical pro-inflammatory cytokines (IL-6 and TNF-α) were detected by quantitative real-time PCR. Aurantio-obtusin significantly decreased the production of NO, PGE2, and inhibited the protein expression of COX-2, TNF-α and IL-6, which were similar to those gene expression of iNOS, COX-2, TNF-α and IL-6 (p < 0.01). Consistent with the pro-inflammatory gene expression, the Aurantio-obtusin efficiently reduced the LPS-induced activation of nuclear factor-κB in RAW264.7 cells. These results suggested that aurantio-obtusin may function as a therapeutic agent and can be considered in the further development of treatments for a variety of inflammatory diseases. Further studies may provide scientific evidence for the use of aurantio-obstusin as a new therapeutic agent for inflammation-related diseases.

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Section: Discussionsupporting

confidence: 64%

Anti-Inflammatory Effects of Aurantio-Obtusin from Seed of Cassia obtusifolia L. through Modulation of the NF-κB Pathway

Hou

Zhao

et al. 2018

Molecules

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“…https://www.omim.org/entry/600456). Given this key role in brain function, NTRK2 has been widely investigated in a range of neuropsychiatric traits and disorders [38][39][40][41][42][43][44][45][46] . The third locus, on chromosome 7, is in Transmembrane Protein 106B, a gene associated with lysosomal enlargement and cell toxicity implicated in depression 8,47 and coronary artery disease 48 .…”

Section: Discussionmentioning

confidence: 99%

A Major Role for Common Genetic Variation in Anxiety Disorders

Purves

Coleman

Meier

et al. 2017

Preprint

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“…NTRK2 is a well characterised gene, and is one of the receptors for Brain Derived Neurotrophic Factor (BDNF). NTRK2 has also been implicated in several neuropsychiatric traits and psychiatric disorders including emotional arousal (Spalek et al, 2016), autism (Correia et al, 2010), suicide (Kohli et al, 2010;Murphy et al, 2011), (Torres et al, 2017), Alzheimer's disease (Chen et al, 2006), alcohol dependence (Xu et al, 2007) and treatment response to antidepressants (Dong, Wong, & Licinio, 2009) and mood stabilisers (Wang et al, 2013). It is important to note that many of these associations have been found in candidate gene studies and are less likely to represent robust findings.…”

Section: Genetic Correlation With External Phenotypesmentioning

confidence: 99%

A major role for common genetic variation in anxiety disorders

et al. 2019

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Anxiety disorders are one of the most common, debilitating and costly classes of psychiatric disorders worldwide. Twin studies estimate heritability of anxiety disorders to be between 30%-60%, depending on specific disorder, age, and level of impairment. Although individual anxiety disorders are considered clinically distinct, they share much of their phenotypic and genetic variance, potentially reflecting an underlying liability distribution. The UK Biobank has collected symptom and disorder level anxiety data on 157,366 individuals across the UK who have contributed their genetic data. We used this dataset to investigate genome-wide associations, SNP based heritability, and genetic correlations in four anxiety phenotypes. These reflect population level current anxiety symptoms as a quantitative phenotype, and three case control phenotypes; severe current anxiety symptoms, probable lifetime generalised anxiety disorder and self-reported lifetime diagnosis of any anxiety disorder. Probable lifetime generalised anxiety disorder and selfreported lifetime diagnosis of any anxiety disorder were meta-analysed with a comparable genome-wide association study of anxiety. Genetic analyses included unrelated Caucasian individuals of Western European ancestry. Estimates of SNP heritability from common variants ranged between 4% (for population level anxiety symptoms) and 32% (for probable generalised anxiety disorder), and all four UK Biobank anxiety phenotypes are highly genetically correlated. Three genome-wide significant loci were found to be associated with anxiety. Both rs3807866 located in the TMEM106B protein coding region on chromosome 7, and rs2996471 located in the NTRK2 protein coding region on chromosome 9, were associated with self-report of any lifetime anxiety diagnosis. An additional non characterised region on chromosome 9 was associated with both self report of any lifetime anxiety diagnosis (rs10809485), and severe anxiety symptoms (rs17189482). Meta-analysis with a comparable genome-wide association study of anxiety did not result in additional findings. This represents the largest genetic study of anxiety to date-however larger sample sizes will be required to further examine the common genetic architecture underlying anxiety. .

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Tyrosine receptor kinase B gene variants (NTRK2 variants) are associated with depressive disorders in temporal lobe epilepsy

Cited by 12 publications

References 50 publications

Anti-Inflammatory Effects of Aurantio-Obtusin from Seed of Cassia obtusifolia L. through Modulation of the NF-κB Pathway

Anti-Inflammatory Effects of Aurantio-Obtusin from Seed of Cassia obtusifolia L. through Modulation of the NF-κB Pathway

A Major Role for Common Genetic Variation in Anxiety Disorders

A major role for common genetic variation in anxiety disorders

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