Teleost fish are known to express two isoforms of P450 aromatase, a key enzyme for estrogen synthesis. One of the isoforms, brain aromatase (AroB),
, is highly expressed during early development of ...zebrafish, thereby suggesting its role in brain development. On the other hand, early development of serotonergic neuron, one of the major monoamine neurons, is considered to play an important role in neurogenesis. Therefore, in this study, we investigated the role of AroB in development of serotonergic neuron by testing the effects of (1) estradiol (E
) exposure and (2) morpholino (MO)-mediated AroB knockdown. When embryos were exposed to E
, the effects were biphasic. The low dose of E
(0.005 µM) significantly increased serotonin (5-HT) positive area at 48 hour post-fertilization (hpf) detected by immunohistochemistry and relative mRNA levels of tryptophan hydroxylase isoforms (
, and
) at 96 hpf measured by semi-quantitative PCR. To test the effects on serotonin transmission, heart rate and thigmotaxis, an indicator of anxiety, were analyzed. The low dose also significantly increased heart rate at 48 hpf and decreased thigmotaxis. The high dose of E
(1 µM) exhibited opposite effects in all parameters. The effects of both low and high doses were reversed by addition of estrogen receptor (ER) blocker, ICI 182,780, thereby suggesting that the effects were mediated through ER. When AroB MO was injected to fertilized eggs, 5-HT-positive area was significantly decreased, while the significant decrease in relative
mRNA levels was found only with
but not with two other isoforms. AroB MO also decreased heart rate and increased thigmotaxis. All the effects were rescued by co-injection with AroB mRNA and by exposure to E
. Taken together, this study demonstrates the role of brain aromatase in development of serotonergic neuron in zebrafish embryos and larvae, implying that brain-formed estrogen is an important factor to sustain early development of serotonergic neuron.
To evaluate the association between estrogen receptor
genes polymorphisms and the risk of ocular disease.
A meta-analysis was performed of all available studies that investigated the association ...between
gene polymorphisms and the risk of ocular disease.
Studies that were selected based on inclusion criteria reported 5 and 4 single-nucleotide polymorphisms (SNPs) identified in the
(ERα) (rs2234093, rs12154178, rs1884054, rs1801132, and rs9340799) and
(ERβ) (rs1268656, rs7159462, rs1256031, and rs4986938) genes, respectively. The pooled result showed a significant association between
rs1256031 gene polymorphism and ocular disease (odds ratio: 0.55, 95% confidence interval: 0.41-0.74, p<0.0001).
The recessive genotype of
rs1256031 gene polymorphism had a protective effect against ocular disease, which supports the hypothesis that the estrogen-signaling pathway through ERβ plays a pivotal role in the pathogenesis of ophthalmic disorders.
Background
Glaucoma is a complex multivariate disorder characterized by retinal ganglion cell (RGC) loss and optic nerve degeneration. Evidence suggests the role of estradiol (E
2
) and the etiology ...of glaucoma. Therefore, this present study evaluates the association between estrogen-signaling pathways and the risk of open-angle glaucoma (OAG).
Results
Meta-analysis was performed from available studies that investigated intraocular pressure (IOP) in patients treated with or without hormone replacement therapy (HRT) and studies that evaluated the associations between estrogen receptor (ER) polymorphisms and the risk of OAG. The pooled result showed that HRT had a positive effect in lowering IOP. Moreover, ERβ polymorphisms showed a significant association with the risk of OAG.
Conclusion
This report supports the notion that estrogen-signaling pathways play a pivotal role in the development of OAG.
Perfluorohexanesulfonic acid (PFHxS) is a highly prevalent environmental pollutant, often considered to be less toxic than other poly- and perfluoroalkyl substances (PFASs). Despite its relatively ...lower environmental impact compared to other PFASs, several studies have suggested that exposure to PFHxS may be associated with disruptions of liver function in humans. Nevertheless, the precise pathomechanisms underlying PFHxS-induced non-alcoholic fatty liver disease (NAFLD) remain relatively unclear. Therefore, this study applied our previously published transcriptome dataset to explore the effects of PFHxS exposure on the susceptibility to NAFLD and to identify potential mechanisms responsible for PFHxS-induced NAFLD through transcriptomic analysis conducted on zebrafish embryos. Results showed that exposure to PFHxS markedly aggravated hepatic symptoms resembling NAFLD and other metabolic syndromes (MetS) in fish. Transcriptomic analysis unveiled 17 genes consistently observed in both NAFLD and insulin resistance (IR), along with an additional 28 genes identified in both the adipocytokine signaling pathway and IR. These shared genes were also found within the NAFLD dataset, suggesting that hepatic IR may play a prominent role in the development of PFHxS-induced NAFLD. In conclusion, our study suggests that environmental exposure to PFHxS could be a potential risk factor for the development of NAFLD, challenging the earlier notion of PFHxS being safer as previously claimed.
The SF3B4 gene encodes a highly conserved protein that plays a critical role in mRNA splicing, and mutations in this gene are known to cause Nager syndrome, a rare craniofacial disorder. Although ...SF3B4 expression is detected earlier in the optic vesicle than in the limb and somite, the role of SF3B4 in the eye is not well understood. We investigate the function of sf3b4 in the retina by performing transcriptome profiles, immunostaining, and behavioral analysis of sf3b4−/− mutant zebrafish. Our findings suggest that dysregulation of the spliceosome complex affects not only craniofacial development but also retinogenesis. Our observation points to the fact that zebrafish lacking functional sf3b4 displayed characteristics similar to retinitis pigmentosa (RP), marked by severe retinal pigment epithelium defects and rod degeneration. Pathway analysis revealed altered retinol metabolism and retinoic acid signaling in the sf3b4−/− mutants. Supplementation of retinoic acid rescued key cellular phenotypes observed in the sf3b4−/− mutants, offering potential therapeutic strategies for RP in the future. In conclusion, our study sheds light on the previously unknown role of SF3B4 in retinogenesis and provides insights into the underlying mechanisms of RP.
Treacher Collins syndrome (TCS, OMIM: 154500) is a rare congenital craniofacial disorder that is caused by variants in the genes TCOF1, POLR1D, POLR1C, and POLR1B. Studies on the association between ...phenotypic variability and their relative variants are very limited. This systematic review summarized the 53 literatures from PubMed and Scopus to explore the potential TCS genotype–phenotype correlations with statistical analysis. Studies reporting both complete molecular genetics and clinical data were included. We identified that the molecular anomaly within TCOF1 (88.71%) accounted for most TCS cases. The only true hot spot for TCOF1 was detected in exon 24, with recurrent c.4369_4373delAAGAA variant is identified. While the hot spot for POLR1D, POLR1C, and POLR1B were identified in exons 3, 8, and 15, respectively. Our result suggested that the higher severity level was likely to be observed in Asian patients harboring TCOF1 variants rather than POLR1. Moreover, common 5‐bp deletions tended to have a higher severity degree in comparison to any variants within exon 24 of TCOF1. In summary, this report suggested the relationship between genetic and clinical data in TCS. Our findings could be used as a reference for clinical diagnosis and further biological studies.
The disease severity in patients with TCOF1 variants was significantly higher in Asians than Caucasians. Asian patients harboring TCOF1 variants were likely more severe than POLR1. Patients with common 5‐bp deletions tended to have a higher severity degree than any variants within exon 24 of TCOF1.
Background
Strong evidence supports the involvement of inflammation processes in the development and progression of Parkinson’s disease (PD), where increasingly correlations have been identified ...between genetic variations in inflammation-related genes and PD. However, data varies between studies. Therefore, we conducted a meta-analysis to clarify associations between inflammation-related gene polymorphisms and PD risk.
Methods
All studies were identified through online databases. Pooled and stratified groups based on racial descent were assembled to evaluate associations between polymorphisms and PD.
Results
The pooled results showed that protective effects for PD were observed for (1) IL-1α -889 C/T in Asian populations (T vs. C, OR = 0.831,
P
= 0.031; TT + CT vs. CC, OR = 0.827,
P
= 0.049); (2) IL-6 -176 G/C in Caucasian populations (CC + GC vs. GG, OR = 0.656,
P
= 0.000; GC vs. GG, OR = 0.673,
P
= 0.000); (3) IL-8 -251 A/T (T vs. A, OR = 0.812,
P
= 0.041; TT vs. AT + AA, OR = 0.663,
P
= 0.012), particularly in Caucasian populations (TT vs. AT + AA, OR = 0.639,
P
= 0.010); (4) IL-10 -819 T/C (C vs. T, OR = 0.742,
P
= 0.034); (5) IL-18 -607 C/A (AA + CA vs. CC, OR = 0.597,
P
= 0.015; CA vs. CC, OR = 0.534,
P
= 0.005), and (6) CCR2 +190 G/A (AA vs. GA + GG, OR = 0.552,
P
= 0.018; AA vs. GG; OR = 0.554; 95% CI 0.336–0.914,
P
= 0.005). An increased risk of PD was associated with IL-10 -1082 G/A in Asian populations (A vs. G, OR = 1.731,
P
= 0.000; AA + GA vs. GG, OR = 1.910,
P
= 0.000). No significant associations with PD were observed for polymorphisms in IL-1β -511 C/T, IL-10 -592 C/A, IL-18 -137 G/C, TNFα -863 C/A, TNFα -857 C/T, TNFα -308 G/A, IFNΥ +874 T/A, and MCP1/CCL2 +2518 A/G.
Conclusions
We suggest that IL-1α -889, IL-6 -176, IL-8 -251, IL-10 -1082, IL-10 -819, IL-18 -607, and CCR2 +190 polymorphisms may be associated with PD risk; however, further studies must verify these conclusions.
Unlike mammals, zebrafish are capable to regenerate many of their organs, however, the response of tissue damage varies across tissues. Understanding the molecular mechanism behind the robust ...regenerative capacity in a model organism may help to identify and develop novel treatment strategies for mammals (including humans). Hence, we systematically analyzed the current literature on the proteome profile collected from different regenerated zebrafish tissues. Our analyses underlining that several proteins and protein families responsible as a component of cytoskeleton and structure, protein synthesis and degradation, cell cycle control, and energy metabolism were frequently identified. Moreover, target proteins responsible for the initiation of the regeneration process, such as inflammation and immune response were less frequently detected. This highlights the limitation of previous proteomic analysis and suggested a more sensitive modern proteomics analysis is needed to unfold the mechanism. This brief report provides a list of target proteins with predicted functions that could be useful for further biological studies.
PDF
