NLRP3 Inflammasome-Mediated Neuroinflammation and Related Mitochondrial Impairment in Parkinson's Disease / 神经科学通报·英文版

Parkinson's disease (PD) is a common neurodegenerative disorder caused by the loss of dopamine neurons in the substantia nigra and the formation of Lewy bodies, which are mainly composed of alpha-synuclein fibrils. Alpha-synuclein plays a vital role in the neuroinflammation mediated by the nucleotide-binding oligomerization domain-, leucine-rich repeat-, and pyrin domain-containing protein 3 (NLRP3) inflammasome in PD. A better understanding of the NLRP3 inflammasome-mediated neuroinflammation and the related mitochondrial impairment during PD progression may facilitate the development of promising therapies for PD. This review focuses on the molecular mechanisms underlying NLRP3 inflammasome activation, comprising priming and protein complex assembly, as well as the role of mitochondrial impairment and its subsequent inflammatory effects on the progression of neurodegeneration in PD. In addition, the therapeutic strategies targeting the NLRP3 inflammasome for PD treatment are discussed, including the inhibitors of NLRP3 inflammatory pathways, mitochondria-focused treatments, microRNAs, and other therapeutic compounds.

Factors Influencing Alzheimer's Disease Risk: Whether and How They are Related to the APOE Genotype / 神经科学通报·英文版

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease featuring progressive cognitive impairment. Although the etiology of late-onset AD remains unclear, the close association of AD with apolipoprotein E (APOE), a gene that mainly regulates lipid metabolism, has been firmly established and may shed light on the exploration of AD pathogenesis and therapy. However, various confounding factors interfere with the APOE-related AD risk, raising questions about our comprehension of the clinical findings concerning APOE. In this review, we summarize the most debated factors interacting with the APOE genotype and AD pathogenesis, depict the extent to which these factors relate to APOE-dependent AD risk, and discuss the possible underlying mechanisms.

How to improve the writing of a medical review paper / 中华神经科杂志

Review article is an important part of medical journals. It provides readers with the latest progress and cutting-edge ideas of medical research, which is of great interests for medical workers. An excellent review is not a simple literature listing. The author not only needs to summarize the important findings and highlights in the literature, but also needs to make a fair evaluation of the current research situation, deeply analyze the deficiencies and put forward his/her own unique views. The purpose is to enable readers to fully and accurately understand the research progress in this field, and inspire the readers to explore ideas, grasp the future direction and carry out innovative research. This paper will focus on how to improve the writing level of medical literature review in the process of topic selection, literature collection and screening, data analysis and evaluation.

Hot Topics in Recent Parkinson's Disease Research: Where We are and Where We Should Go / 神经科学通报·英文版

Parkinson's disease (PD), the second most common neurodegenerative disease, is clinically characterized by both motor and non-motor symptoms. Although overall great achievements have been made in elucidating the etiology and pathogenesis of PD, the exact mechanisms of this complicated systemic disease are still far from being clearly understood. Consequently, most of the currently-used diagnostic tools and therapeutic options for PD are symptomatic. In this perspective review, we highlight the hot topics in recent PD research for both clinicians and researchers. Some of these hot topics, such as sleep disorders and gut symptoms, have been neglected but are currently emphasized due to their close association with PD. Following these research directions in future PD research may help understand the nature of the disease and facilitate the discovery of new strategies for the diagnosis and therapy of PD.

Recent Progress in Non-motor Features of Parkinson’s Disease with a Focus on Circadian Rhythm Dysregulation / 神经科学通报·英文版

Parkinson’s disease (PD) is the second most common neurodegenerative disease, which manifests with both motor and non-motor symptoms. Circadian rhythm dysregulation, as one of the most challenging non-motor features of PD, usually appears long before obvious motor symptoms. Moreover, the dysregulated circadian rhythm has recently been reported to play pivotal roles in PD pathogenesis, and it has emerged as a hot topic in PD research. In this review, we briefly introduce the circadian rhythm and circadian rhythm-related genes, and then summarize recent research progress on the altered circadian rhythm in PD, ranging from clinical features to the possible causes of PD-related circadian disorders. We believe that future comprehensive studies on the topic may not only help us to explore the mechanisms of PD, but also shed light on the better management of PD.

Hot Topics in Recent Parkinson’s Disease Research: Where We are and Where We Should Go / 神经科学通报·英文版

Parkinson’s disease (PD), the second most common neurodegenerative disease, is clinically characterized by both motor and non-motor symptoms. Although overall great achievements have been made in elucidating the etiology and pathogenesis of PD, the exact mechanisms of this complicated systemic disease are still far from being clearly understood. Consequently, most of the currently-used diagnostic tools and therapeutic options for PD are symptomatic. In this perspective review, we highlight the hot topics in recent PD research for both clinicians and researchers. Some of these hot topics, such as sleep disorders and gut symptoms, have been neglected but are currently emphasized due to their close association with PD. Following these research directions in future PD research may help understand the nature of the disease and facilitate the discovery of new strategies for the diagnosis and therapy of PD.

Postmortem analysis of vagus nerve pathology and intestinal neuroinflammation in Parkinson's disease / 中华神经科杂志

Objective To investigate the roles of neuroinflammation and pathology of peripheral nervous system in the pathogenesis of Parkinson's disease (PD).Methods Immunohistochemical staining was performed to examine the nodose ganglia (containing vagus nerve) and intestine of an autopsy case of PD.The neuroinflammation and morphological changes of vagus nerve and enteric nervous system were observed.Results The expressions and distributions of glial fibrillary acidic protein and ionized calcium binding adapter molecule 1,two typical glia cell biomarkers,were different in vagus nerve and intestinal mucosa.Tumor necrosis factor α and inducible nitric oxide synthase were expressed in intestinal mucosa and myenteric plexus of the PD patient.There was a strong inflammatory reaction in the myenteric plexus,which distributed diffusely.Conclusion Satellite glial cells and intestinal inflammatory response may play a role in the pathogenesis of PD.

Impacts of chronic sleep deprivation on learning and memory, autophagy and neuronal apoptosis in mice / 中华神经科杂志

Objective To establish chronic sleep deprivation mouse model,evaluate the learning and memory ability of mice and observe autophagy and apoptosis levels in mouse brain.Methods C57BL/6 mice (n =20) were randomly separated into sleep deprivation group and control group.After 2-month sleep deprivation by using an adapted multiple platform method,the behavioral performance of mice was measured by IntelliCage system.The expression of microtubule associated protein 1 light chain 3-Ⅱ (LC3-Ⅱ) and Beclin-1 was detected by Western blotting.Confocol microscopy was used to observe autophagosome.In addition,terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining was performed to detect neuronal apoptosis level in mouse brain.Results The results of behavioral test showed that the incorrect visit ratio was much higher in sleep deprivation group than that in control group.Moreover,the expression of LC3-Ⅱ (sleep deprivation group 1.681 ± 0.186,control group 1.125 ±0.048,t =2.892,P =0.027 6) and Beclin-1 (sleep deprivation group 1.144 ±0.048,control group 1.006 ± 0.017,t =2.721,P =0.018 6) in mouse hippocampus and cortex was significantly elevated in sleep deprivation group than those in control group.Accordingly,the confocal microscopy observation also revealed an increased nuclear LC3-positive puncta in hippocampus and cortex of sleep deprived mice (hippocampus in sleep deprivation group 1.665 ± 0.153,in control group 0.819 ± 0.072,t =5.024,P =0.002 4;cortex in sleep deprivation group 1.925 ± 0.175,in control group 1.195 ± 0.111,t =3.521,P =0.012 5).In addition,TUNEL staining showed a much higher percentage of TUNEL-positive nuclei in these brain regions (hippocampus in sleep deprivation group 47.24 ± 4.15,in control group 19.26 ± 3.72,t =5.025,P =0.007 4;cortex in sleep deprivation group 42.25 ± 1.25,in control group 27.50 ± 3.23,t =4.262,P =0.005 3).Conclusions Chronic sleep deprivation can impair the learning and memory,increase the expression of LC3-Ⅱ and Beclin-1,elevate the formation of autophagosome,and promote apoptosis in mouse brain.These findings suggest that autophagy and apoptosis might be involved in the cognitive impairment induced by chronic sleep deprivation.

Change of reactive oxygen species production in co-culture model of rat astrocytes and motor neurons VSC 4.1 / 中国病理生理杂志

AIM: To explore the mutual effect of co-culture of wild-type astrocytes (ASC) and motor neurons VSC4.1 (VSC) on the respective ability to produce reactive oxygen species (ROS). METHODS: The inhibition rates of cell growth in ASC and VSC in co-culture or independent culture was detected after exposed to excitatory stimulus by MTT method. Real-time observation of ROS production by ASC and VSC labeled with Hoechst 33342 was detected by confocal microscopy under the conditions of co-culture or independent culture. RESULTS: Higher concentration of glutamate induced a higher inhibition rate in mixed cell growth than that in ASC alone, while lower concentration of glutamate induced a higher inhibition rate in mixed cell growth than that in VSC only. Real-time observation by confocal microscopy showed that ROS production by VSC under the condition of co-culture, which showed a notable increase at 15 min, was significant less than that in independent culture, which peaked at 5 min and was gradually decreased. ROS production by ASC in co-culture began to increase significantly at 10 min. CONCLUSION: Compared to independent culture, ASC reduces the resting ROS production by co-cultured with VSC, while ASC prolongs the duration of ROS production by VSC after exposed to excitatory stimulus.

Experimental destruction of dopaminergic neurons initiated by lipopolysaccharide / 中华老年医学杂志

Objective To investigate lipopolysaccharide(LPS)-induced injury of dopaminergic neurons in the substantia nigra and effect of LPS on animals behavior in vitro and in vivo. Methods Pheochromocytoma(PC12)cell viability was estimated by MTT assay after cells had been differently incubated in medium containing LPS, 6-OHDA and culture supernatant of LPS-treated microglia. LPS was stereotactically injected into left substantia nigra of rats. 14,21 and 28 days after injection, the circling behavior was observed by intraperitoneal injection of apomorphine. Midbrain dopaminergic neurons were identified by using tyrosine hydroxylase (TH) immunohistochemistry. The contents of dopamine and its metabolites in the striatum and substantia nigra were measured by high performance liquid chromatography(HPLC). Results LPS alone had no influence on cell viability. However, the 26% and 30% reduction of cell viability was found when cells were exposed to culture supernatant of LPS-treated microglia and 6-OHDA. The circling behavior ipsilateral to LPS-treated side was induced in some rats 21 and 28 days following injection, but not 14 days. Compared with the PBS-treated rats, the marked (35%~60%) loss of TH-positive cells in left substantia nigra was identified 21 and 28 days after LPS treatment, but not 14 days. The 30%~70% reduction of dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) in left striatum and substantia nigra was found at 21 and 28 days following injection, whereas no significant change was observed at 14 days. Conclusions LPS could indirectly injury the dopaminergic neurons and induce behavioral asymmetry of rats.

Effects of nitric oxide on PC12 cell apoptosis induced by rotenone / 第三军医大学学报

Objective To investigate the roles of nitric oxide and caspase 3 in PC12 cell apoptosis induced by rotenone. Methods The acute injury effect of rotenone on PC12 cells and viability of the PC12 cells were detected by MTT assay. Nitrite (NO 2 -) was quantified by Greiss reaction. The activity of caspase 3 and the cell apoptosis were detected by fluoremetry and agarose gel electrophoresis, respectively. Results The MTT colorimetry indicated that PC12 cell viability reached a peak at 7 d after passage. L NAME at the concentration of 100 ?mol/L showed the strongest protective effect for PC12 cell in the four different doses. Rotenone also induced the formation of DNA ladder in PC12 cells. Additionally, the nitric oxide synthase inhibitor L NAME inhibited the activity of caspase 3 protease. L NAME also inhibited the production of nitric oxide induced by rotenone. Conclusion Nitric oxide and caspase 3 are involved in the process of PC12 cell apoptosis induced by rotenone.