A metabolome atlas of mouse brain on the global metabolic signature dynamics following short-term fasting.

Calorie restriction (CR) or a fasting regimen is considered one of the most potent non-pharmacological interventions to prevent chronic metabolic disorders, ameliorate autoimmune diseases, and attenuate aging. Despite efforts, the mechanisms by which CR improves health, particularly brain health, are still not fully understood. Metabolic homeostasis is vital for brain function, and a detailed metabolome atlas of the brain is essential for understanding the networks connecting different brain regions.

Nanotherapeutic and Stem Cell Therapeutic Strategies in Neurodegenerative Diseases: A Promising Therapeutic Approach.

Neurodegeneration is characterized by progressive, disabling, and incurable neurological disorders with the massive loss of specific neurons. As one of the most promising potential therapeutic strategies for neurodegenerative diseases, stem cell therapy exerts beneficial effects through different mechanisms, such as direct replacement of damaged or lost cells, secretion of neurotrophic and growth factors, decreased neuroinflammation, and activation of endogenous stem cells. However, poor survival and differentiation rates of transplanted stem cells, insufficient homing ability, and difficulty tracking after transplantation limit their further clinical use.

Intrastriatal injection of Parkinson's disease intestine and vagus lysates initiates α-synucleinopathy in rat brain.

Parkinson's disease (PD) is characterized by the selective loss of dopaminergic neurons in the midbrain and the pathological accumulation of misfolded α-synuclein (α-syn) in the brain. A growing body of evidence suggests that the formation of misfolded α-syn and aggregation may begin in the peripheral nervous system, specifically the enteric nervous system, and then propagate to the central nervous system via the vagus nerve. However, the PD-like neuropathology induced by the intestine and vagus nerve extracts is rarely investigated.

PM2.5 exposure triggers cell death through lysosomal membrane permeabilization and leads to ferroptosis insensitivity via the autophagy dysfunction/p62-KEAP1-NRF2 activation in neuronal cells.

PM2.5 exposure can be associated with the onset of neurodegenerative diseases, with oxidative stress-induced cellular homeostasis disruption and cell death as one of the main mechanisms. However, the exact cellular and molecular processes are still rarely investigated.

deficiency promotes age-dependent alterations in striatal medium spiny neurons.

Background: The classical motor symptoms of Parkinson's disease (PD) are tightly linked to the gradual loss of dopamine within the striatum. Concomitantly, medium spiny neurons (MSNs) also experience morphological changes, such as reduced dendritic complexity and spine density, which may be potentially associated with motor dysfunction as well. Thus, MSNs may serve as the emerging targets for PD therapy besides the midbrain dopaminergic neurons.

Risk of ischemic stroke in patients with COVID-19 infection: A systematic review and meta-analysis.

An ongoing global pandemic, the coronavirus disease 2019 is posing threat to people all over the world. The association between COVID-19 and the risk of ischemic stroke remains unclear. This study systematically reviewed published studies and conducted meta-analysis to evaluate the association between the risk of ischemic stroke and COVID-19.

The significance of sialylation on the pathogenesis of Alzheimer's disease.

Sialylation, one of the most common and complex modes of glycosylation, corresponds with the development of the infant brain and nervous system. The most prevalent neurodegenerative disease is Alzheimer's disease (AD), which is mainly characterized by cognitive decline and behavioral disorders. However, the relationship between sialylation and AD occurrence is poorly understood.

Tetrahedral DNA nanostructures functionalized by multivalent microRNA132 antisense oligonucleotides promote the differentiation of mouse embryonic stem cells into dopaminergic neurons.

MicroRNA132 (miR132) negatively regulates the differentiation of mouse embryonic stem cells (ESCs) into dopaminergic (DAergic) neurons; in contrast, antisense oligonucleotide against miR132 (miR132-ASO) effectively blocks the activity of endogenous miR132 and thereafter promotes the differentiation of DAergic neurons. However, it is difficult for miR132-ASO to enter cells without a suitable delivery system. Tetrahedral DNA nanostructures (TDNs), as a new type of DNA-based nanocarrier, have great potential in biomedical applications and even have been reported to promote stem cell differentiation.

Activation of dopamine receptor D1 inhibits glioblastoma tumorigenicity by regulating autophagic activity.

Purpose: Recent studies have reported important roles of dopamine receptors in the early development and progression of glioblastoma (GBM). Here, we tested the antitumor activity of a Dopamine receptor D1 (DRD1) agonist, either alone or in combination with temozolomide (TMZ) on GBM cells.

Methods: Immunofluorescence, immunohistochemistry and Western blotting were used to detect dopamine receptor expression in primary human GBM tissues.

α-Synuclein Negatively Regulates Nurr1 Expression Through NF-κB-Related Mechanism.

The nuclear receptor-related 1 protein (Nurr1) is critical for the development and survival of midbrain dopamine neurons that are predominantly affected and progressively degenerated in Parkinson's disease (PD). The expression level of Nurr1 has been proposed to be modulated by α-synuclein (α-SYN), an important pathological hallmark of PD. However, the underlying molecular mechanisms of α-SYN-Nurr1 interaction are still rarely explored.

Piperine regulates glycogen synthase kinase-3β-related signaling and attenuates cognitive decline in D-galactose-induced aging mouse model.

Aging-related cholinergic dysfunction, extensive neuroinflammation and oxidative stress in brain are predominant pathogenic factors for dementia. In the present study, we aimed to evaluate the protective effects of piperine, an alkaloid nutrient component of Piper nigrum, against cognitive impairment in a senescent mouse model induced by D-galactose (D-Gal) and to explore the underlying mechanisms. Senescent mouse model was established by repeated subcutaneous injection of D-Gal (150 mg/kg, once daily for 42 days).

Piperine attenuates cognitive impairment in an experimental mouse model of sporadic Alzheimer's disease.

Piperine, the major alkaloid constituent of black pepper, has been reported to possess a wide range of pharmacological effects on the central nervous system, including antidepressant, anticonvulsant and anti-ischemic activities. In the present study, we aimed to investigate the therapeutic potential and neuroprotective mechanisms of piperine in an experimental mouse model of sporadic Alzheimer's disease (sAD) induced by intracerebroventricular (ICV) infusion of streptozotocin (STZ). STZ was infused bilaterally at a dose of 1.

Elevated Plasma microRNA-105-5p Level in Patients With Idiopathic Parkinson's Disease: A Potential Disease Biomarker.

Parkinson's disease (PD) is the second most common neurodegenerative disease, which still lacks a biomarker to aid in diagnosis and to differentiate diagnosis at the early stage of the disease. microRNAs (miRNAs) are small and evolutionary conserved non-coding RNAs that are involved in post-transcriptional gene regulation. Several miRNAs have been proposed as potential biomarkers in several diseases.

Altered Expression Levels of MicroRNA-132 and Nurr1 in Peripheral Blood of Parkinson's Disease: Potential Disease Biomarkers.

MicroRNAs (miRNAs) are small and evolutionary conserved noncoding RNAs that are involved in post-transcriptional gene regulation. Differential expression levels of miRNAs can be used as potential biomarkers of disease. Previous animal studies have indicated that the expression level of miR-132 is negatively correlated with its downstream molecule nuclear receptor related 1 protein (Nurr1), which is one of the key factors for the maintenance of dopaminergic function and is particularly vulnerable in Parkinson's disease (PD).

Concentration Levels, Biological Enrichment Capacities and Potential Health Risk Assessment of Trace Elements in Eichhornia crassipes from Honghu Lake, China.

This study investigated the concentrations of Zn, Cu, Cr, Pb, As and Cd in different tissues of E. crassipes from Honghu Lake. The total concentrations of trace elements in E.

Alterations of and Cytokines in the Peripheral Blood Mononuclear Cells: Combined Biomarkers for Parkinson's Disease.

Nuclear receptor related 1 protein (), a transcription factor as key player for maintaining dopamine neuron functions and regulating neuroinflammation in the central nerves system, is a potential susceptibility gene for Parkinson's disease (PD). To ascertain whether the expression levels of gene and inflammatory cytokines are altered in patients with PD, we measured their mRNA levels in the peripheral blood mononuclear cells (PBMCs) in 312 PD patients, 318 healthy controls (HC), and 332 non-PD neurological disease controls (NDCs) by quantitative real-time PCR. Our data showed that gene expression was significantly decreased in the PBMCs of PD as compared with that of HC and NDC ( < 0.

Potential biomarkers of Parkinson's disease revealed by plasma metabolic profiling.

The plasma of Parkinson's disease (PD) patients may contain various altered metabolites associated with the risk or progression of the disease. Characterization of the abnormal metabolic pattern in PD plasma is therefore critical for the search for potential PD biomarkers. We collected blood plasma samples from PD patients and used an LC-MS based metabolomics approach to identify 17 metabolites with significantly altered levels.

Heavy metals and metalloid distribution in different organs and health risk assessment for edible tissues of fish captured from Honghu Lake.

Honghu Lake is the seventh largest freshwater lake in China, and fishery is one of the most important economic sources for local inhabitants. Toxic metal concentrations in muscle of all analyzed fish species captured from Honghu Lake were generally below China standards, except Cr in crucian carp. The average concentrations were decreased in the following order, Zn (14.

CpG demethylation in the neurotoxicity of 1-methyl-4-phenylpyridinium might mediate transcriptional up-regulation of α-synuclein in SH-SY5Y cells.

The accumulation of α-synuclein is the primary pathological hallmark of Parkinson's disease (PD). In PD patients, CpG demethylation of intron-1 has been reported to be associated with α-synuclein up-regulation. Environmental factor, for example neurotoxin, is a major etiological risk factor in PD pathogenesis.

Tiny But Mighty: Promising Roles of MicroRNAs in the Diagnosis and Treatment of Parkinson's Disease.

Parkinson's disease (PD) is the second most common age-related neurodegenerative disorder after Alzheimer's disease. To date, the clinical diagnosis of PD is primarily based on the late onset of motor impairments. Unfortunately, at this stage, most of the dopaminergic neurons may have already been lost, leading to the limited clinical benefits of current therapeutics.

Gold nanoparticles enhance the differentiation of embryonic stem cells into dopaminergic neurons via mTOR/p70S6K pathway.

Aim: This study aimed to investigate the effect of gold nanoparticles (AuNPs) on differentiation of mouse embryonic stem cells (ESCs) into dopaminergic (DA) neurons and explore the possible underlying molecular mechanisms.

Materials & Methods: The efficiency of AuNPs on DA neuron differentiation was evaluated by observing fluorescence in TH promoter-engineered GFP-reporter ESCs, western blot and real-time PCR. The possible signal pathway was determined by western blot.

Aberrant CpG Methylation Mediates Abnormal Transcription of MAO-A Induced by Acute and Chronic L-3,4-Dihydroxyphenylalanine Administration in SH-SY5Y Neuronal Cells.

L-3,4-dihydroxyphenylalanine (L-dopa) remains the most effective drug for therapy of Parkinson's disease (PD); however, long-term use of it causes serious side effects. L-dopa-induced dyskinesia (LID) has consistently been related to L-dopa-derived excessive dopamine release, but the mechanisms have not been addressed very clear. Monoamine oxidase A (MAO-A) is one of the key enzymes in dopamine metabolism and therefore may be involved in L-dopa-induced side effects.

Double-Edged Roles of Nitric Oxide Signaling on APP Processing and Amyloid-β Production In Vitro: Preliminary Evidence from Sodium Nitroprusside.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is thought to be caused in part by the age-related accumulation of amyloid-β (Aβ) in the brain. Recent findings have revealed that nitric oxide (NO) modulates the processing of amyloid-β precursor protein (APP) and alters Aβ production; however, the previously presented data are contradictory and the underlying molecular mechanisms are still incomplete. Here, using human SH-SY5Y neuroblastoma cells stably transfected with wild-type APPwt695, we found that NO, derived from NO donor sodium nitroprusside (SNP), bi-directionally modulates APP processing in vitro.

Hypoxia-inducible factor-1α regulates the expression of L-type voltage-dependent Ca(2+) channels in PC12 cells under hypoxia.

Hypoxia is an important factor in regulation of cell behavior both under physiological and pathological conditions. The mechanisms of hypoxia-induced cell death have not been completely elucidated yet. It is well known that Ca(2+) is critically related to cell survival.