Toxoplasma gondii is an intracellular protozoan parasite that infects approximately one third of the human popu- lation worldwide. Considering the toxicity and side effects of anti-toxoplasma medications, it is important to develop effec- tive drug alternatives with fewer and less severe off-target effects. In this study, we found that 4-hydroxybenzaldehyde (4- HBA) induced autophagy and the expression of NAD-dependent protein deacetylase sirtuin-1 (SIRT1) in primary murine bone marrow-derived macrophages (BMDMs). Interestingly, treatment of BMDMs with 4-HBA significantly reduced the number of macrophages infected with T. gondii and the proliferation of T. gondii in infected cells. This effect was impaired by pretreating the macrophages with 3-methyladenine or wortmannin (selective autophagy inhibitors) or with sirtinol or EX527 (SIRT1 inhibitors). Moreover, we found that pharmacological inhibition of SIRT1 prevented 4-HBA-mediated expres- sion of LC3-phosphatidylethanolamine conjugate (LC3-II) and the colocalization of T. gondii parasitophorous vacuoles with autophagosomes in BMDMs. These data suggest that 4-HBA promotes antiparasitic host responses by activating SIRT1- mediated autophagy, and 4-HBA might be a promising therapeutic alternative for the treatment of toxoplasmosis.

OBJECTIVE: This study aimed to compare the accuracy of subjective memory complaints, informant-reports for cognitive declines, and their combination for screening cognitive disorders in memory clinic setting. METHODS: One-hundred thirtytwo cognitively normal (CN), 136 mild cognitive impairment (MCI), and 546 dementia who visited the memory clinic in the Seoul National University Hospital underwent standardized clinical evaluation and comprehensive neuropsychological assessment. The Subjective Memory Complaints Questionnaire (SMCQ) and the Seoul Informant Report Questionnaire for Dementia (SIRQD) were used to assess subjective memory complaints and informant-reports for cognitive declines, respectively. RESULTS: Both SMCQ and SIRQD showed significant screening ability for MCI, dementia, and overall cognitive disorder (CDall: MCI plus dementia) (screening accuracy: 60.1–94.6%). The combination of SMCQ and SIRQD (SMCQ+SIRQD) was found to have significantly better screening accuracy compared to SMCQ alone for any cognitive disorders. SMCQ+SIRQD also significantly improved screening accuracy of SIRQD alone for MCI and CDall, but not for dementia. CONCLUSION: Our findings suggest that the combined information of both subjective memory complaints and informant-reports for cognitive declines can improve MCI screening by each individual information, while such combination appears not better than informant-reports in regard of dementia screening.
Aged ; Dementia ; Humans ; Mass Screening* ; Memory* ; Mild Cognitive Impairment ; Seoul