Comorbidity of white matter lesions in parkinson's disease: a study on risk factors and phenotypic differences.

BACKGROUND: Comorbidity of white matter lesions (WMLs) in idiopathic Parkinson's disease (PD) is becoming increasingly common. OBJECTIVE: To analyze the risk factors and phenotypic differences for the occurrence and severity of WMLs in patients with PD. METHODS: A total of 123 PD patients underwent clinical, laboratory, and magnetic resonance imaging (MRI) evaluations. RESULTS: PD patients with WMLs were found to have a higher association with age, Modified Hoehn & Yahr stage (H-Y stage), and hypertension. There was a certain correlation between the severity of WMLs and PD phenotypes. 89% of PD patients had periventricular hyperintensities (PVH). Additionally, the score of the modified version of the Scheltens visual rating scale of PVH in the postural instability gait difficulty (PIGD) phenotype of PD was significantly higher than that in the tremor-dominant (TD) phenotype. The Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores in the PIGD group were significantly lower than those in the TD group. Furthermore, compared with the TD group, the serum homocysteine level was significantly higher in the PIGD group. CONCLUSIONS: Age, H-Y stage, and hypertension are independent risk factors for WMLs in PD, and the severity of WMLs is related to the phenotype of PD patients. Our study found that PVH is the most common occurrence of WMLs in Parkinson's disease, and the burden of PVH is significantly higher in the PIGD phenotype compared to the TD phenotype of PD. Additionally, the PIGD phenotype is associated with more severe cognitive decline and elevated homocysteine levels.

Sleep disorders in Wilson's disease: a questionnaire study.

OBJECTIVE: To examine the clinical characteristics and influencing factors related to sleep disorders in patients with Wilson's disease (WD), and investigate its potential mechanisms. METHODS: A total of 150 patients with WD (76 hepatic, 42 neurological, 32 asymptomatic form) and 150 age- and sex-matched control subjects were investigated using 3 standardized sleep questionnaires. Differences among 3 subtypes were discussed. RESULTS: The mean Parkinson's disease sleep scale (PDSS) score of WD was lower than the controls (Z = - 4.426, P = 0.000), and their mean Epworth Sleepiness Scale (ESS) score as well as Pittsburgh sleep quality index (PSQI) score of WD was higher than that of the controls (t = 2.005, P = 0.048; t = 3.342, P = 0.001). The incidence of excessive daytime sleepiness (EDS) in WD group were significantly higher than the controls (X2 = 6.064, P = 0.014). Further analysis showed that total PDSS score of neurologic presentation group was lower than others (X2 = 6.131, P = 0.047), while the ESS score was higher (F = 3.817, P = 0.029). UWDRS showed a negative correlation with PDSS (r = - 0.440, P = 0.022) and has a higher negative correlation with PDSS in neurologic presentation group (r = - 0.732, P = 0.000). CONCLUSIONS: Patients with WD often suffer from sleep disturbances, mainly characterized by difficulty falling asleep, difficulty staying asleep, nocturnal motor symptoms (numbness, cramps, tremor), and daytime dozing. And the incidence of EDS is significantly higher than that of the controls. Sleep quality is worse in patients with WD of neurologic presentation than the other two groups. Furthermore, the worse of the symptoms, patients with WD suffer more serious of the sleep disorders especially in neurologic presentation group.

Felbamate produces antidepressant-like actions in the chronic unpredictable mild stress and chronic social defeat stress models of depression.

Felbamate is an anticonvulsant used in the treatment of epilepsy. In this study, we investigated the antidepressant-like actions of felbamate in mice. The effects of felbamate were first assessed using the forced swimming test (FST) and tail suspension test (TST), and then investigated in the chronic unpredictable mild stress (CUMS) and chronic social defeat stress (CSDS) models of depression. The changes in the hippocampal brain-derived neurotrophic factor (BDNF) signaling cascade after chronic stress and felbamate treatment were also examined. It was found that felbamate exhibited antidepressant-like activities in the FST and TST without affecting the locomotor activity of mice. Felbamate was also effective in both the CUMS and CSDS models of depression. Moreover, felbamate administration fully restored the decreased hippocampal BDNF signaling pathway in both the CUMS-stressed and CSDS-stressed mice. Collectively, felbamate has antidepressant-like actions in mice involving the hippocampal BDNF system.

Matrine Exerts Antidepressant-Like Effects on Mice: Role of the Hippocampal PI3K/Akt/mTOR Signaling.

BACKGROUND: Current antidepressants in clinical use always take weeks or even months to exert full therapeutic effects, and sometimes have serious side effects. Thus, it is very necessary to develop novel antidepressants with better efficacy and fewer adverse effects. The present study focused on investigating the antidepressant potential of matrine and its possible mechanisms of action. METHODS: The forced swim test, tail suspension test, and chronic unpredictable mild stress model of depression were used to reveal the antidepressant-like effects of matrine on mice. Western blotting, immunohistochemistry, and lentivirus were further used together to explore the antidepressant mechanism of matrine. RESULTS: It was found that matrine exhibited significant antidepressant actions in the forced swim test and tail suspension test without affecting the locomotor activity of mice. Chronic matrine administration fully reversed the chronic unpredictable mild stress-induced depressive-like symptoms in forced swim test, tail suspension test, and sucrose preference test. After that, western blotting analysis revealed that chronic matrine treatment restored the decreasing effects of chronic unpredictable mild stress on the PI3K/Akt/mammalian target of rapamycin signaling in hippocampus, but not prefrontal cortex. Furthermore, pharmacological and genetic blockade of the PI3K/Akt/mammalian target of rapamycin signaling in hippocampus abolished the antidepressant actions of matrine on mice. CONCLUSIONS: Taken together, matrine produces antidepressant-like effects on mice via promoting the hippocampal PI3K/Akt/ mammalian target of rapamycin signaling.

Antidepressant-like effects of ginsenoside Rg3 in mice via activation of the hippocampal BDNF signaling cascade.

Current antidepressants are clinically effective only after several weeks of administration. Ginsenoside Rg3 is one component of ginsenosides, with a similar chemical structure to ginsenoside Rg1. Here, we investigated the antidepressant effects of Rg3 in mouse models of depression. The antidepressant actions of Rg3 were first examined in the forced swim test (FST) and tail suspension test (TST), and then assessed in the chronic social defeat stress (CSDS) model of depression. The changes in the hippocampal brain-derived neurotrophic factor (BDNF) signaling pathway after CSDS and Rg3 treatment were investigated. A tryptophan hydroxylase inhibitor and a BDNF signaling inhibitor were also used to determine the pharmacological mechanisms of Rg3. It was found that Rg3 produced antidepressant effects in the FST and TST without affecting locomotor activity. Rg3 also prevented the CSDS-induced depressive-like symptoms. Moreover, Rg3 fully restored the CSDS-induced decrease in the hippocampal BDNF signaling pathway, and use of the BDNF signaling inhibitor blocked the antidepressant effects of Rg3. In conclusion, ginsenoside Rg3 has antidepressant effects via promotion of the hippocampal BDNF signaling pathway.

WY14643 Attenuates the Scopolamine-Induced Memory Impairments in Mice.

WY14643 is a selective agonist of peroxisome proliferator-activated receptor-α (PPAR-α) with neuroprotective and neurotrophic effects. The aim of this study was to evaluate the effects of WY14643 on cognitive impairments induced by scopolamine, a muscarinic acetylcholine receptor antagonist. We conducted different behavior tests including the Y-maze, Morris water maze, and passive avoidance test to measure the cognitive functions of C57BL/6J mice after scopolamine and WY14643 treatment. It was found that WY14643 injection significantly attenuated the scopolamine-induced cognitive impairments in these behavioral tests. Moreover, WY14643 treatment significantly enhanced the expression of brain-derived neurotrophic factor (BDNF) signaling cascade in the hippocampus. The usage of both PPAR-α inhibitor GW6471 and BDNF system inhibitor K252a fully prevented the memory-enhancing effects of WY14643. Therefore, these findings suggest that WY14643 could improve the scopolamine-induced memory impairments, and these effects are mediated by the activation of PPAR-α and BDNF system, thereby exhibiting a cognition-enhancing potential.