Objectives Many researchers have expected pioglitazone to serve as an effective neuroprotective agent against Parkinson’s disease (PD). Therefore, we conducted this cohort study to investigate the association between pioglitazone use and PD by using a large Asian population-based dataset in Taiwan. Design Retrospective cohort study. Setting Taiwan. Participants 7906 patients with diabetes who had received pioglitazone were defined as the study cohort, and 7906 matched patients with diabetes who had not received pioglitazone were defined as the comparison cohort. Primary and secondary outcome measures We tracked each patient individually over a 5-year follow-up period to identify those diagnosed as having PD during this period. We performed Cox proportional hazard regression analyses to evaluate the HRs for PD between the study and comparison cohorts. Results The findings indicated that among the sampled patients, PD occurred in 257 (1.63%): 119 (1.51%) pioglitazone users and 138 (1.75%) non-users. The adjusted HR for PD within the follow-up period was 0.90 (95% CI: 0.68 to 1.18) in the patients who had received pioglitazone compared with the matched patients who had not received pioglitazone. Moreover, this study revealed that pioglitazone use was not associated with PD incidence in men (HR: 1.06, 95% CI: 0.71 to 1.59) or women (HR: 0.84, 95% CI: 0.61 to 1.15). Conclusions This study did not find the relationship between pioglitazone use and PD incidence, regardless of sex, among an Asian population of patients with diabetes.

Serotonin (5-HT) plays a crucial role in modulating the afferent fiber discharge rate in the inferior colliculus, auditory cortex, and other nuclei of the ascending auditory system. Resveratrol, a natural polyphenol phytoalexin, can inhibit serotonin transporters (SERT) to increase synaptic 5-HT levels. In this study, we investigated the effects of resveratrol on noise-induced damage in the serotonergic system. Male Sprague-Dawley rats were anaesthetized and exposed to an 8-kHz tone at 116 dB for 3.5 h. Resveratrol (30 mg/kg, intraperitoneal injection [IP]) and citalopram (20 mg/kg, IP), a specific SERT inhibitor used as a positive control, were administered once a day for four consecutive days, with the first treatment occurring 2 days before noise exposure. Auditory brainstem response testing and positron emission tomography (PET) with N,N-dimethyl-2-(2-amino-4-[¹⁸F]fluorophenylthio)benzylamine (4-[¹⁸F]-ADAM, a specific radioligand for SERT) were used to evaluate functionality of the auditory system and integrity of the serotonergic system, respectively, before and after noise exposure. Finally, immunohistochemistry was performed 1 day after the last PET scan. Our results indicate that noise-induced serotonergic fiber loss occurred in multiple brain regions including the midbrain, thalamus, hypothalamus, striatum, auditory cortex, and frontal cortex. This noise-induced damage to the serotonergic system was ameliorated in response to treatment with resveratrol and citalopram. However, noise exposure increased the hearing threshold in the rats regardless of drug treatment status. We conclude that resveratrol has protective effects against noise-induced loss of SERT.