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The role of cell transplantation therapy and gene therapy in the treatment of Parkinson's disease (PD) has attracted more and more attention. It has developed from laboratory research tools to clinical products for patients. The purpose of cell transplantation therapy in PD is to replace degenerated midbrain dopamine neurons and restore dopamine neurotransmission in the denervation of the nigrostriatal pathway. Gene therapy works by introducing genetic material to slow down the degeneration of dopamine neurons and restore dopaminergic signaling transduction. Using neurotrophic factor and delivery methods for neurotrophic factor have entered clinical trials. It can also intervene in the pathological process of α⁃synuclein (α⁃Syn) mediated neurodegeneration. This paper reviews the latest progress of cell transplantation therapy and gene therapy for PD, and looks forward to the future treatment strategies.

Objective: Because resveratrol (RSV) has been shown to improve learning and memory, so we investigated the potential benefit of RSV on learning and memory deficits in juvenile mice fed with a HC diet and explored the molecular mechanisms underlying this process. Methods: Six-week-old C57BL/6J mice were divided into three different diet groups: control, HC diet, and HC + RSV diet. Serum insulin and insulin-like growth factor 1 (IGF-1) levels were measured using enzyme-linked immunosorbent assays. Protein expression was examined by immunohistochemistry and western blotting. Results: Administration of RSV daily (30 mg/kg) prevented the HC diet-induced increase in juvenile animal body weight but did not improve any other physiological conditions, including fasting blood glucose and serum cholesterol, triglyceride, insulin, and IGF-1 levels. However, RSV did prevent learning and memory deficits in the HC group. Peroxisome proliferator-activated receptor gamma (PPARγ) was downregulated in the CA1 region of the hippocampus in both the HC and HC + RSV groups, but the reduction was significantly greater in the HC + RSV group (P < .01 compared with the HC group). Moreover, although the HC diet reduced the number of p16-positive neurons, the HC + RSV diet significantly upregulated p16 expression in the CA1 region of the hippocampus (P < .01 compared with the HC group). Conclusions: RSV protected against learning and memory impairments in juvenile animals fed with a HC diet, possibly via upregulation of p16 or downregulation of PPARγ in the hippocampal CA1 region. [ABSTRACT FROM AUTHOR]

Dietary composition may influence neuronal function as well as processes underlying synaptic plasticity. In this study, we aimed to determine the effect of high and low caloric diets on a mouse model of learning and memory and to explore mechanisms underlying this process. Mice were divided into three different dietary groups: normal control (n = 12), high-caloric (HC) diet (n = 12), and low-caloric (LC) diet (n = 12). After 6 months, mice were evaluated on the Morris water maze to assess spatial memory ability. We found that HC diet impaired learning and memory function relative to both control and LC diet. The levels of SIRT1 as well as its downstream effectors p53, p16, and peroxisome proliferator-activated receptor γ (PPARγ) were decreased in brain tissues obtained from HC mice. LC upregulated SIRT1 but downregulated p53, p16, and PPARγ. The expressions of PI3K and Akt were not altered after HC or LC diet treatment, but both LC and HC elevated the levels of phosphorylated-cAMP response element-binding protein (p-CREB) and IGF-1 in hippocampal CA1 region. Therefore, HC diet-induced dysfunction in learning and memory may be prevented by caloric restriction via regulation of the SIRT1-p53 or IGF-1 signaling pathways and phosphorylation of CREB. [ABSTRACT FROM AUTHOR]

The NLRP3 inflammasome is involved in the neuroinflammatory pathway of Alzheimer's disease (AD). The aim of this study is to explore the roles and underlying mechanisms of ginkgolide (Baiyu®) on amyloid precursor protein (APP)/presenilin 1 (PS1) transgenic mice and a murine microglial cell line, BV-2. In the present study, the APP/PS1 mice were administered with ginkgolide, followed by a Morris water maze test. The mice were then euthanized to obtain brain tissue for histological and Aβ analysis. Additionally, BV-2 cells were pretreated with ginkgolide and then incubated with Aβ1-42 peptide. NLRP3, ASC, and caspase-1 mRNA and protein expression in brain tissue of mice and BV-2 cells were quantified by real-time PCR and western blotting, as well as reactive oxygen species (ROS) production, interleukin (IL)-1β and IL-18 levels by lucigenin technique and ELISA. Compared with the APP/PS1 mice, ginkgolide-treated mice demonstrated the shortened escape latency, reduced plaques, less inflammatory cell infiltration and neuron loss in the hippocampi of APP/PS1 mice. The levels of NLRP3, ASC, caspase-1, ROS, IL-1β, and IL-18 were also decreased in the brain tissue of APP/PS1 mice or Aβ1-42-treated BV-2 cells following ginkgolide treatment. Ginkgolide exerted protective effects on AD, at least partly by inactivating the NLRP3/caspase-1 pathway.

Abstract: Various studies have revealed an association between cigarette smoking and increased risk for multiple sclerosis (MS). However, its role in neuromyelitis optica spectrum disorder (NMOSD) remains elusive. Therefore, in the present case-control study, we aimed to assess the association of active and passive cigarette smoking with the risk of MS and NMOSD.Thirty-six patients with NMOSD, 46 patients with MS, and 122 healthy individuals were included in this study. Standardized questionnaires and telephone interviews were used to collect information regarding the active and passive cigarette smoking behaviors of the patients and normal controls.The risk of MS was significantly higher among smokers than among nonsmokers (odds ratio = 2.166, 95% confidence interval: 1.109-4.170; P = .027). Further analysis of the risk between active and passive smokers, male smokers and nonsmokers showed no statistical difference. However, neither smokers nor active smokers had a greater or lower risk of NMOSD than their nonsmoking counterparts.Our preliminary study showed no significant association between cigarette smoking and the risk of NMOSD, strongly suggesting that, unlike MS, cigarette smoking might not confer NMOSD susceptibility, at least in the Northern Han Chinese population., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Recent studies indicated that different caloric intake may influence neuronal function. Excessive caloric intake associated with accelerated aging of the brain and increased the risk of neurodegenerative disorders. And low caloric intake (caloric restriction, CR) could delay aging, and protect the central nervous system from neurodegenerative disorders. The underlying mechanisms remain poorly understood. In this study, thirty six-week-old male C57/BL male mice were randomly divided into three different dietary groups: normal control (NC) group (fed standard diet), CR group (fed low-caloric diet) and high-calorie (HC) group (fed high-caloric diet). After 10 months, spatial memory ability was determined by Morris water maze. Pathological changes of the hippocampus cells were detected with HE and Nissl staining. The expression of proteins involved in autophagy in the hippocampus was determined by immunofluorescence and Western blot. The result of Morris water maze showed that the learning and memory capacity significantly increased in the CR group, and significantly decreased in the HC group. HE and Nissl staining showed cells damaged obviously in the HC group. The expression of mTOR and p62 was increased in the HC group, and decreased in the CR group. The expression of Beclin1, LC3 and cathepsin B was decreased in the HC group, and increased in the CR group. Our findings demonstrate that long-term high caloric intake is a risk factor that can significantly contribute to the development of neurological disease via suppressing autophagy, and CR may prevent age-related learning ability impairment via activating autophagy in mice.