Introduction Depression might increase the risk of erectile dysfunction (ED), and ED might further exacerbate depression. The causal relationship between these two diseases remains controversial. In addition, limited evidence is available regarding the age-dependent and time-dependent effects on the association of depression and ED. Aim We investigated the hypothesis that ED increases the risk of depression by using a nationwide Taiwanese population-based claims database. In addition, we assessed the age-dependent and time-dependent effects on the association of depression and ED. Methods A longitudinal cohort study was conducted to determine the association between patients with ED and depression development during a 5-year follow-up period, using claims data from the Taiwanese National Health Insurance Research Database. Main Outcome Measures The study cohort comprised patients who were diagnosed with ED during 1997 to 2005 (N = 2,527). For a comparison cohort, 5 age- and sex-matched patients for every patient in the study cohort were selected using random sampling (N = 12,635). All of the patients were followed-up for 5 years from the date of cohort entry to identify the development of depression. Results The main finding of this study was that patients with ED are at an increased risk of developing depression. The adjusted hazard ratio (AHR) for depression was 2.24-fold higher in the patients with ED than in the comparison cohort (95% confidence interval [CI]: 1.83–2.74; P < 0.001). Regarding the time-dependent effect, the incidence of depression was highest during the first year of follow-up (AHR: 3.03, 95% CI = 2.08–4.40; P < 0.001). Conclusions This study demonstrates that patients with ED are at a higher longitudinal risk of developing depression in Asian men, particularly within the first year after the diagnosis of ED.

Age-related degenerative brain diseases frequently manifest as memory de cits. Dietary interventions or nutraceuticals may provide e cacious treatments through prevention and cure. Soybean meal, a byproduct of soy oil re ning, has health bene ts, but its effect on memory function is unknown. Therefore, we evaluated the effect of the oral administration of soybean meal extract (SME) for 2 weeks on memory function using the Morris water maze (MWM) test in healthy rats and investigated the possible underlying mechanisms. First, analysis of the composition revealed that SME is rich in iso avones; SME did not exhibit hepatotoxicity or renal toxicity at the different doses tested. The MWM results revealed that the escape latency and movement distance of rats were signi cantly shorter in the SME group than in the control group, indicating that SME can help in memory preservation. In addition, SME increased the levels of presynaptic proteins such as synaptophysin, synaptobrevin, synaptotagmin, syntaxin, synapsin I, and 25-kDa synaptosome-associated protein as well as protein kinases and their phosphorylated expression, including extracellular signal-regulated kinases 1 and 2 (ERK1/2), protein kinase C (PKC), and Ca 2+ /calmodulin-dependent protein kinase II (CaMKII)] in the hippocampal nerve terminals (synaptosomes). Transmission electron microscopy also indicated that SME increased the number of synaptic vesicles in hippocampal synaptosomes. Furthermore, SME rats exhibited increased gut microbiota diversity and altered microbiota composition compared with control rats. Therefore, our data suggest that SME can increase presynaptic function and modulate gut microbiota, thus aiding in memory preservation in rats.

Excessive glutamate release is known to be involved in the pathogenesis of neurological diseases, and suppression of glutamate release from nerve terminals is considered to be a treatment strategy. In this study, we investigated whether isosaponarin, a flavone glycoside isolated from wasabi leaves, could affect glutamate release in rat cerebral cortex nerve terminals (synaptosomes). The release of glutamate was evoked by the K+ channel blocker 4-aminopyridine (4-AP) and measured by an online enzyme-coupled fluorimetric assay. Isosaponarin produced a concentration-dependent inhibition of 4-AP-evoked glutamate release with a half-maximum inhibition of release value of 22 μM. The inhibition caused by isosaponarin was prevented by eliminating extracellular Ca2+ or by using bafilomycin A1, an inhibitor of synaptic vesicle exocytosis. Isosaponarin decreased intrasynaptosomal rises in Ca2+ levels that were induced by 4-AP, without affecting the synaptosomal membrane potential. The isosaponarin-induced inhibition of glutamate release was significantly prevented in synaptosomes that were pretreated with a combination of the calcium channel blockers ω-conotoxin GVIA (N-type) and ω-agatoxin IVA (P/Q-types). The protein kinase C (PKC) pan-inhibitor GF109203X and the Ca2+-dependent PKC inhibitor Go6976 abolished the inhibition of glutamate release by isosaponarin, while the Ca2+-independent PKC inhibitor rottlerin did not show any effect. The results from immunoblotting assays also showed that isosaponarin lowered PKC, PKCα, synaptosomal-associated protein of 25 kDa (SNAP-25), and myristoylated alanine-rich C-kinase substrate (MARCKS) phosphorylation induced by 4-AP. In addition, FM1-43-labeled synaptic vesicles in synaptosomes showed that treatment with isosaponarin resulted in an attenuation of the 4-AP-induced decrease in fluorescence intensity that is consistent with glutamate release. Transmission electron microscopy of synaptosomes also provided evidence that isosaponarin altered the number of synaptic vesicles. These results indicate that isosaponarin suppresses the Ca2+-dependent PKC/SNAP-25 and MARCKS pathways in synaptosomes, causing a decrease in the number of available synaptic vesicles, which inhibits vesicular glutamate release from synaptosomes.