These findings revealed that honokiol has both protective and therapeutic effects on motor impairments and dopaminergic progressive damage, at least in part through modulation of NOS signaling, in 6-OHDA-lesioned mice. Honokiol may represent a potential therapeutic candidate for the management of motor symptoms and neurodegeneration in PD.
Parkinson's disease (PD) is a profound neurodegenerative disorder with gradual loss of dopamine nigrostriatal neurons linked to serious behavioral symptoms. While the current treatment strategies present limitations on halting the progression of PD, this study aimed to investigate the therapeutic potential of honokiol, as a partial peroxisome proliferator-activated receptor-gamma (PPARγ) mimic, on the proceeding behavioral and biochemical alterations in hemiparkinsonian mice. Results showed that unilateral striatal 6-hydroxydopamine (6-OHDA)-lesioned mice exhibited motor impairment, reflecting the contralateral rotation induced by apomorphine at 1-3 weeks post-lesion. Subchronic honokiol administration for 1-2 weeks, beginning 7 days after 6-OHDA-lesion, dose-dependently ameliorated motor dysfunction in hemiparkinsonian mice. Recovery of motor function was correlated with reversal of nigrostriatal dopaminergic neuronal loss, accompanied by higher tyrosine hydroxylase (TH) density, dopamine transporter (DAT) expression and vesicular monoamine transporter-2 (VMAT2) levels. Furthermore, honokiol attenuated oxidative stress and reactive astrocyte induction via decreasing NADPH-oxidase and glial fibrillary acidic protein (GFAP) expressions in 6-OHDA-lesioned striatum. The reversal effects of honokiol on behavioral impairment and striatal PPARγ expression were impeded by PPARγ antagonist GW9662. Notably, subchronic honokiol treatment extended the lifespan of these hemiparkinsonian mice. The present findings demonstrate the therapeutic activities of honokiol in ameliorating motor impairment and progressive dopaminergic damage that could be associated with regulating PPARγ signaling. Therefore, honokiol may potentially exert as a novel therapeutic candidate through PPARγ activation for management of motor symptoms and progressive neurodegeneration in PD.
Background:The World Health Organization (WHO) proposed the integrated care for older people (ICOPE) screening tool to identify functional impairment. We explore the association of geriatric functional impairment and hypertension, diabetes, dyslipidemia in the community-dwelling elderly. Methods: We enrolled individuals aged at least 65 with hypertension, diabetes, or dyslipidemia; or those aged at least 75 from May to July 2019. We applied ICOPE tools to evaluate six function assessments: cognitive decline, limited mobility, malnutrition, visual impairment, hearing loss, and depressive symptoms. Factors were analyzed using stepwise multivariable linear regression for ICOPE scores and logistic regression for geriatric functional impairment. All analyses were adjusted for age and glomerular filtration rate. Results: We enrolled 457 participants including 303 (66.3%) participants with hypertension, 296 (64.8%) diabetes, and 221 (48.4%) dyslipidemia. Seventy-eight (17.1%) participants have at least one geriatric functional impairment, including 41 (25.9%) participants aged ≥ 75 and 37 (12.4%) aged 65-74. The ICOPE score (0.4 ± 0.6) of participants aged at least 75 was higher than that (0.1 ± 0.4) of the participants aged 65-74 (p < 0.001). Dyslipidemia (p = 0.002) was positively associated with ICOPE score. Dyslipidemia (odds ratio: 2.15, 95% confidence interval: 1.27-3.70, p = 0.005), not hypertension (p = 0.3) and diabetes (p = 0.9), was associated with geriatric functional impairment. Visual impairment was the most common function impairment. Female was linked to limited mobility, renal function was associated with mobility (p < 0.001) and nutrition (p = 0.02). Conclusion: Dyslipidemia but not hypertension, diabetes is linked to geriatric functional impairment in community-dwelling elderly. Lower renal function is associated with decreased mobility and nutrition. More studies are needed to determine if treatment of dyslipidemia reduces geriatric functional impairment.
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