Introduction: Respiratory dysfunction in patients with Parkinson’s disease (PD) could present in the early stage and worsen in the late stages. These changes could be a factor affecting the ability of daily living and quality of life of patients with PD. The primary objective of this study was to assess the respiratory function and its association with motor function in patients with different stages of PD. Methods: This was a cross-sectional study conducted at the Huashan Hospital of Fudan University in Shanghai, China. The study included 65 patients diagnosed with PD (the Hoehn and Yahr scale between 1 and 4) and 20 healthy individuals of similar age, gender, weight, and height. The ventilatory function was assessed using the spirometry. Motor function was evaluated using subscale III of the United Parkinson’s disease rating scale (UPDRS-III). After confirming the normality of data distribution, we performed one-way ANOVA with a Tukey’s post hoc test. Results: Compared with the healthy individuals, there was no statistical significance in forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) in the H&Y 1 group and H&Y 2 group (p > 0.05) but reduced peak expiratory flow (PEF) in the H&Y 2 group (p = 0.002). Reduced FVC, FEV1, and PEF was seen in the H&Y 3 group (p = 0.002, p = 0.001, and p = 0.0001, respectively). Reduced FVC, FEV1, PEF, and FEF25–75% was seen in the H&Y 4 group (p = 0.001, p = 0.0001, p = 0.0001, and p = 0.025, respectively). The correlation analysis revealed that there was a significant negative correlation between FVC and UPDRS-III scores (r = −0.248, p = 0.046), disease duration (r = −0.276, p = 0.026), H&Y scale (r = −0.415, p = 0.001). FEV1 was negatively correlated with UPDRS-III scores (r = −0.277, p = 0.025), disease duration (r = −0.291, p = 0.019), H&Y scale (r = −0.434, p = 0.0001). FEF25–75% was negatively correlated with disease duration (r = −0.247, p = 0.047), H&Y scale (r = −0.278, p = 0.025). Conclusion: Our findings revealed that respiratory impairment is present in moderate and advanced PD patients, and directly related to the severity of the disease. It is important to conduct respiratory function test in the clinical practice.

帕金森病(Parkinson's disease,PD)是第二大常见的神经退行性疾病,其临床特征表现为静止性震颤、运动迟缓、肌强直和姿势不稳[1].PD患者的发病年龄在21-40岁称为青年型帕金森病(young-onset PD,YOPD)[2],这一类患者由于发病时处于壮年时期,疾病的持续时间更长,运动并发症也更多,会带来更大的生理、心理和经济的压力[3].此外,与晚发型患者相比,YOPD患者往往还有工作的需求及更多的社会角色.基于这些差异,YOPD患者成为了一个独特的群体,同时治疗上也需要更个性化的方法.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive degeneration of midbrain dopaminergic neurons. The miR-29s family, including miR-29a and miR-29b1 as well as miR-29b2 and miR-29c, are implicated in aging, metabolism, neuronal survival, and neurological disorders. In this study, the roles of miR-29a/b1 in aging and PD were investigated. miR-29a/b1 knockout mice (named as 29a KO hereafter) and their wild-type (WT) controls were used to analyze aging-related phenotypes. After challenged with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), dopaminergic injuries, glial activation, and mouse behaviors were evaluated. Primary glial cells were further cultured to explore the underlying mechanisms. Additionally, the levels of miR-29s in the cerebrospinal fluid (CSF) of PD patients (n = 18) and healthy subjects (n = 17) were quantified. 29a KO mice showed dramatic weight loss, kyphosis, and along with increased and deepened wrinkles in skins, when compared with WT mice. Moreover, both abdominal and brown adipose tissues reduced in 29a KO mice, compared to their WT counterpart. However, in MPTP-induced PD mouse model, the deficiency of miR-29a/b1 led to less severe damages of dopaminergic system and mitigated glial activation in the nigrostriatal pathway, and subsequently alleviated the motor impairments in 3-month-old mice. Eight-month-old mutant mice maintained such a resistance to MPTP intoxication. Mechanistically, the deficiency of miR-29a/b-1 promoted the expression of neurotrophic factors in 1-Methyl-4-phenylpyridinium (MPP+)-treated primary mixed glia and primary astrocytes. In lipopolysaccharide (LPS)-treated primary microglia, knockout of miR-29a/b-1 inhibited the expression of inflammatory factors, and promoted the expression of anti-inflammatory factors and neurotrophic factors. Knockout of miR-29a/b1 increased the activity of AMP-activated protein kinase (AMPK) and repressed NF-κB/p65 signaling in glial cells. Moreover, we found miR-29a level was increased in the CSF of patients with PD. Our results suggest that 29a KO mice display the peripheral premature senility. The combined effects of less activated glial cells might contribute to the mitigated inflammatory responses and elicit resistance to MPTP intoxication in miR-29a/b1 KO mice.

目的 分析男性脊髓损伤患者阴茎勃起功能障碍的相关因素.方法 2019年12月至2021年1月,本院男性脊髓损伤患者28例,采用RigiScan检测患者夜间睡眠勃起阴茎的硬度和围度活动指数.根据患者尿道球海绵体反射、肛门自主收缩、肛门触觉和肛门压觉存在与否将患者分组,比较组间硬度和围度活动指数.结果 存在尿道球海绵体反射、肛门自主收缩、肛门触觉和肛门深压觉的患者,硬度和围度活动指数较高(|t|>2.19,P<0.05).结论 脊髓损伤患者的尿道球海绵体反射、肛门自主收缩、肛门触觉和肛门深压觉反应可初步预判患者阴茎勃起功能损伤.

Studies reveal a linkage of miR-29s in aging and Parkinson’s disease (PD). Here we show that the serum levels of miR-29s in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice exhibited dynamic changes. The role of miR-29b2/c in aging and PD was studied utilizing miR-29b2/c gene knockout mice (miR-29b2/c KO). miR-29b2/c KO mice were characterized by a markedly lighter weight, kyphosis, muscle weakness and abnormal gait, when compared with wild-type (WT) mice. The WT also developed apparent dermis thickening and adipose tissue reduction. However, deficiency of miR-29b2/c alleviated MPTP-induced damages of the dopaminergic system and glial activation in the nigrostriatal pathway and consequently improved the motor function of MPTP-treated KO mice. Knockout of miR-29b2/c inhibited the expression of inflammatory factors in 1-methyl-4-phenylpyridinium (MPP+)-treated primary cultures of mixed glia, primary astrocytes, or LPS-treated primary microglia. Moreover, miR-29b2/c deficiency enhanced the activity of AMPK but repressed the NF-κB p65 signaling in glial cells. Our results show that miR-29b2/c KO mice display the progeria-like phenotype. Less activated glial cells and repressed neuroinflammation might bring forth dopaminergic neuroprotection in miR-29b2/c KO mice. Conclusively, miR-29b2/c is involved in the regulation of aging and plays a detrimental role in Parkinson’s disease.

We aimed to examine whether miRNA-29s (miR-29s) in serum are associated with cognitive impairment in Parkinson's disease (PD). Thirty-nine PD patients with normal cognition (PD-NC), 37 PD patients with mild cognitive impairment (PD-MCI), 22 PD patients with dementia (PDD) and 40 healthy controls were recruited. Detailed clinical evaluations and a schedule of neuropsychological tests were administered to all patients. MiR-29s expression in serum samples was assessed using reverse-transcription quantitative real-time PCR. We found that the levels of all three miR-29s in the PDD group were significantly lower than those in the PD-NC group (p < 0.05). In addition, the miR-29b level was downregulated in the PD-MCI group with respect to that in the PD-NC group (p < 0.05). After adjusting for years of education and the UPDRS-III subscore using a multivariate model, miR-29s showed significant associations with PDD. MiR-29b levels were shown to be associated with different subsets of PD cognition and could accurately discriminate PDD from non-PDD (area under the curve (AUC) = 0.859; 95% CI, 0.7817-0.9372). Further analysis of the cognitive domains found that the miR-29s levels were all associated with memory performance in PD patients. In summary, miR-29s are associated with cognitive impairment in PD.

Objective Stem cell transplantation is a promising strategy with great potential to treat Parkinson’s disease (PD). Nevertheless, improving the cell delivery route and optimising implanted cells are necessary to increase the therapeutic effect. Herein, we investigated whether intranasal delivery of bone marrow stromal cells (BMSCs) has beneficial effects in a PD mouse model and whether the therapeutic potential of BMSCs could be enhanced by preconditioning with fasudil. Methods A PD mouse model was developed by intraperitoneally administering 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Mice were treated intranasally with phosphate buffered saline (PBS), BMSCs, or BMSCs preconditioned with fasudil. One month later, the effects of BMSC treatment were analysed. Results Our study showed that fasudil could accelerate the proliferation of BMSCs and promote brain-derived neurotrophic factor (BDNF) secretion in vitro. Intranasally administered BMSCs were capable of surviving and migrating in the brain. Intranasal delivery of BMSCs preconditioned with fasudil significantly improved motor function and reduced dopaminergic neuron loss in substantia nigra; treatment with BMSCs and PBS resulted in similar outcomes. Preconditioning with fasudil inhibited the activation and aggregation of microglia, suppressed immune response, and reinforced BDNF secretion in MPTP-PD mice significantly more than treatment with BMSCs alone. Conclusion The present study demonstrates that intranasally administering BMSCs preconditioned with fasudil is a promising cell-based therapy for PD.

Epidemiological and clinicopathological studies indicate that there is a high risk for chronic heart failure ( CHF ) in patients suffering from neuropsychiatric disorders, such as depression. However, it is unclear whether CHF causes depression, and the underlying mechanisms of this association remain largely unknown. In this study, mice with myocardial infarction and CHF were used to investigate behavioral alterations as well as changes in the brain‐heart axis. During the first 6 months, abnormalities in neuropsychiatric behaviors were detected in mice with CHF . Using the sucrose preference test, a 9 months course of CHF resulted in two subgroups: mice with a significant decrease in sucrose preference, defined herein as “susceptible” (Sus), and mice with a normal sucrose preference, defined herein as “resilient.” Compared to the resilient and sham‐operated animals, the Sus mice displayed imbalances in glutamate transmission and hypothalamic–pituitary–adrenal axis activation, abnormal synaptic plasticity, and increased inflammatory responses. Furthermore, abnormal kynurenine metabolism was detected in Sus mice. Our results suggest that long‐term CHF increases inflammatory responses in the central nervous system and leads to depression in Sus mice.

Regulated endocrine-specific protein, 18 kDa (RESP18) was first cloned in 1994. Its function in the brain especially in neurodegenerative diseases remains unclear. In this study, RESP18 knockout (KO) and littermate wild-type (WT) mice were comprehensively analyzed. The dopaminergic toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was applied to generate subchronic Parkinson's disease model. We found that KO mice displayed a reduction in locomotor activity and motor coordination under physiological conditions. Five and six days after MPTP administration, the behavioral impairments were detected in MPTP-treated WT mice, whereas such impairments were not detected in MPTP-treated KO mice. The depletion of tyrosine hydroxylase-positive nerve fibers in the striatum was similar between MPTP-treated KO mice and WT littermates. Furthermore, the striatal level of α-synuclein protein was increased by treatment with MPTP in WT mice, but not in KO mice. The loss of dopaminergic neurons was markedly alleviated, and the activation of glial cells was inhibited in the substantia nigra of KO mice challenged with MPTP. These results suggested that RESP18 deficiency might protect dopaminergic neurons against MPTP toxicity.

Parkinson's disease (PD) is a common and progressive neurodegenerative disorder. The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD is widely used to study the progression of this disease. Behavior impairment is closely related to the damage of the dopaminergic system in the basal ganglia. Here, MPTP-induced changes in mouse behavior and glial activation were evaluated at different time points after the treatment and the long-term changes in the nigrostriatal pathway were analyzed. We found that mice exposed to MPTP displayed a full recovery in the rotarod test and the pole test but not in the wire hanging test at 65 days post-injection. A biphasic activation of microglial cells was revealed in the nigrostriatal pathway of MPTP-treated mice. However, activation of astrocytes displayed an approximately bell-shaped kinetics and an approximately S-shaped kinetics in the striatum and the substantia nigra, respectively. In addition, the numbers of complement component 3 (C3)-positive neurotoxic astrocytes in the substantia nigra of MPTP-treated mice increased with time and reached a maximum at 42 days, and declined at 74 days, after the treatment. Three months later, the dopaminergic system was partially recovered from the lesion of MPTP. The time course of pathophysiological events has important implications for the interventions or treatment of PD. (C) 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

There is currently no reliable and easily applicable diagnostic marker for Parkinson's disease (PD). The aims of the present study were to compare the expression profiles of the microRNA29 family (miR-29s) in blood serum from patients with PD with healthy controls and to clarify whether the expression of miR-29s is correlated with disease severity, duration or L-dopa therapy and whether expression depends on the gender and age of patients. The levels of blood serum miR-29s in 80 patients with PD and 80 unaffected controls were assessed by reverse transcription-quantitative real-time PCR. The PCR products were confirmed by cloning and sequencing. Additionally, the expression of miR-7 in the blood serum from PD patients and control subjects was assessed. Serum miR-29 levels were significantly downregulated in PD patients compared to healthy controls. The serum miR-29 levels in female PD patients were markedly higher than in male PD patients. The expression of serum miR-29a and miR-29c expression tended to decrease with disease severity. Moreover, we found that serum miR-7 levels did not differ between PD patients and control subjects. Therefore, the reduction of serum miR-29 levels, particularly miR-29a and miR-29c, warrants further investigation of its potential serving as biomarkers for PD.

The characteristic brain pathology and motor and nonmotor symptoms of Parkinson's disease (PD) are well established. However, the details regarding the causes of the disease and its course are much less clear. Animal models have significantly enriched our current understanding of the progression of this disease. Among various neurotoxin-based models of PD, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model is the most commonly studied model. Here, we provide an overview of the dynamic changes in the nigrostriatal pathway in the MPTP mouse model of PD. Pathophysiological events, such as reductions in the striatal dopamine (DA) concentrations and levels of the tyrosine hydroxylase (TH) protein, depletion of TH-positive nerve fibers, a decrease in the number of TH-positive neurons in the substantia nigra pars compacta (SNpc), and glial activation, are addressed. This article will assist with the development of interventions or therapeutic strategies for PD.

Microglial activation and inflammation are associated with progressive neuronal apoptosis in neurodegenerative disorders such as Parkinson’s disease (PD). γ-Aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system, has recently been shown to play an inhibitory role in the immune system. Tiagabine, a piperidine derivative, enhances GABAergic transmission by inhibiting GABA transporter 1 (GAT 1). In the present study, we found that tiagabine pretreatment attenuated microglial activation, provided partial protection to the nigrostriatal axis and improved motor deficits in a methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. The protective function of tiagabine was abolished in GAT 1 knockout mice that were challenged with MPTP. In an alternative PD model, induced by intranigral infusion of lipopolysaccharide (LPS), microglial suppression and subsequent neuroprotective effects of tiagabine were demonstrated. Furthermore, the LPS-induced inflammatory activation of BV-2 microglial cells and the toxicity of conditioned medium toward SH-SY5Y cells were inhibited by pretreatment with GABAergic drugs. The attenuation of the nuclear translocation of nuclear factor κB (NF-κB) and the inhibition of the generation of inflammatory mediators were the underlying mechanisms. Our results suggest that tiagabine acts as a brake for nigrostriatal microglial activation and that it might be a novel therapeutic approach for PD.

Heart failure (HF) and Parkinson's disease (PD) are growing health problems due in part to population aging. Autonomic nervous system dysfunction has been recognized as a feature of PD and neuroimaging studies indicate that cardiac sympathetic denervation occurs more commonly in PD patients than in non-PD controls [ 1 Orimo S. et al. (123)I-metaiodobenzylguanidine myocardial scintigraphy in Parkinson's disease. J Neurol Neurosurg Psychiatry. 1999; 67: 189-194 Crossref PubMed Scopus (316) Google Scholar , 2 Goldstein D.S. et al. Cardiac sympathetic denervation in Parkinson disease. Ann Intern Med. 2000; 133: 338-347 Crossref PubMed Scopus (307) Google Scholar ]; The prevalence of heart failure was twice as high in elderly PD patients compared to non-PD patients (20% vs 9%) [ [3] Zesiewicz T.A. et al. Heart failure in Parkinson's disease: analysis of the United States medicare current beneficiary survey. Parkinsonism Relat Disord. 2004; 10: 417-420 Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar ]; however, the effect of coronary heart disease/HF on the occurrence of PD is controversial in three large hospital admission datasets [ [4] Turner M.R. et al. Cardiovascular fitness as a risk factor for amyotrophic lateral sclerosis: indirect evidence from record linkage study. J Neurol Neurosurg Psychiatry. 2012; 83: 395-398 Crossref PubMed Scopus (53) Google Scholar ]. We aimed to study the relationship between the strike of HF and the progression of PD in mouse models.