Background: Mesenchymal stem cells (MSCs)-derived extracellular vesicles (EVs) have been reported to exhibit therapeutic effects in various animal models of neurological diseases, such as stroke and hypoxic-ischemic brain injury. Objective: The present study investigated the potential beneficial effect of MSC-derived EVs in an animal model of Alzheimer’s disease (AD). Methods: APP/PS1 mice and their non-transgenic littermates (WT) received intracerebroventricle injection of MSC-derived EVs once per two days for two weeks. Then novel object recognition and water maze tasks were carried out to measure the cognitive behaviors. Electrophysiological tests were carried out to measure hippocampal synaptic plasticity. Inducible nitric oxide synthase (iNOS) mRNA and protein levels were measured by qRT-PCR and western blotting in primary cultured neurons treated with amyloid-β peptide (Aβ) or prepared from APP/PS1 mice. Results: Treatment with MSC-derived EVs alleviates exogenous Aβ-induced iNOS mRNA and protein expression. In cultured primary neurons prepared from APP/PS1 pups, iNOS mRNA and protein levels were significantly reduced when treated with MSC-derived EVs. MSC-derived EVs improved cognitive behavior, rescued impairment of CA1 synaptic transmission, and long-term potentiation in APP/PS1 mice. Conclusion: MSC-derived EVs possessed beneficial effects in a mouse model of AD, probably by suppressing Aβ induced iNOS expression.

The ketogenic diet (KD) is a low-carbohydrate, high-fat and adequate-protein diet. As a diet mimicking fasting, it triggers the production of ketone bodies (KBs) and brings the body into a state of ketosis. Recent and accumulating studies on humans and animal models have shown that KD is beneficial to neurodegenerative diseases through modulating central and peripheral metabolism, mitochondrial function, inflammation, oxidative stress, autophagy, and the gut microbiome. Complicated interplay of metabolism, gut microbiome, and other mechanisms can regulate neuroinflammation in neurodegenerative diseases by activating multiple molecular and cellular pathways. In this review, we detail the physiological basis of the KD, its functions in regulating neuroinflammation, and its protective role in normal brain aging and neurodegenerative diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington’s disease (HD). We aimed to elucidate the underlying neuroinflammatory mechanisms of KD therapies in neurodegenerative diseases and provide novel insights into their application for neurodegenerative disease prevention and treatment.

Parkinson’s disease (PD) is a chronic, progressive and debilitating disease, which affects over 2.5 million people in China. PD is characterized clinically by resting tremor, muscular rigidity, bradykinesia and postural instability. As the disease progresses, additional complications can arise such as non-motor and neurobehavioral symptoms. Pharmacological treatment and surgical intervention for PD have been implemented in China. Until 10 years ago, there was lack of standardization for the management of PD in different regions and among different physicians, leading to different treatment levels in different regions and different physicians. Since then, the Chinese Parkinson’s Disease and Movement Disorder Society have published three versions of guidelines for the management of PD in China, in 2006, 2009 and 2014, respectively. Correspondingly, the overall level of treatment for PD in China improved. To update the treatment guidelines based on current foreign and domestic practice guidelines and clinical evidence, and to improve the treatment options available to physicians in the management of PD. A variety of treatment recommendations in the treatment guidelines have been proposed, including physical activity and disease-modifying medication, which should be initiated at the early-stage of the disease. The principles of dosage titration should be followed to avoid acute adverse reactions to the drugs, to achieve a satisfactory clinical effect with a low dose and to reduce the incidence of long-term motor complications. Moreover, different treatment strategies should be considered at different stages of the disease. Importantly, treatment guidelines and personalized treatments should be valued equally. A set of treatment recommendations has been developed to assist physicians to improve and optimize clinical outcomes for patients with PD in China.

Sun X, et al. J Clin Neurol. 2020 Oct;16(4):530-546. https://doi.org/10.3988/jcn.2020.16.4.530

The ketogenic diet (KD) is a low‐carbohydrate, high‐fat regime that is protective against neurodegenerative diseases. However, the impact of KD on Parkinson's disease (PD) and its mechanisms remains unclear. 1‐Methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐induced mouse model of PD was fed with KD for 8 weeks. Motor function and dopaminergic neurons were evaluated. Inflammation in the brain, plasma, and colon tissue were also measured. Fecal samples were assessed by 16S rDNA gene sequencing and untargeted metabolomics. We found that KD protected motor dysfunction, dopaminergic neuron loss, and inflammation in an MPTP mouse model of PD. 16S rDNA sequencing revealed that MPTP administration significantly increased Citrobacter, Desulfovibrio, and Ruminococcus, and decreased Dubosiella, whereas KD treatment reversed the dysbiosis. Meanwhile, KD regulated the MPTP‐induced histamine, N‐acetylputrescine, d‐aspartic acid, and other metabolites. Fecal microbiota transplantation using feces from the KD‐treated mice attenuated the motor function impairment and dopaminergic neuron loss in antibiotic‐pretreated PD mice. Our current study demonstrates that KD played a neuroprotective role in the MPTP mouse model of PD through the diet–gut microbiota–brain axis, which may involve inflammation in the brain and colon. However, future research is warranted to explore the explicit anti‐inflammatory mechanisms of the gut–brain axis in PD models fed with KD.