Transcriptomic atlas of midbrain dopamine neurons uncovers differential vulnerability in a Parkinsonism lesion model

eLife, Год журнала: 2023, Номер 12

Опубликована: Авг. 14, 2023

Midbrain dopamine (mDA) neurons comprise diverse cells with unique innervation targets and functions. This is illustrated by the selective sensitivity of mDA substantia nigra compacta (SNc) in patients Parkinson’s disease, while those ventral tegmental area (VTA) are relatively spared. Here, we used single nuclei RNA sequencing (snRNA-seq) approximately 70,000 mouse midbrain to build a high-resolution atlas neuron diversity at molecular level. The results showed that differences between groups could best be understood as continuum without sharp subtypes. Thus, assigned several ‘territories’ ‘neighborhoods’ within shifting gene expression landscape where boundaries gradual rather than discrete. Based on enriched patterns these territories neighborhoods, were able localize them adult midbrain. Moreover, because underlying mechanisms for variable sensitivities pathological insults not well understood, analyzed surviving after partial 6-hydroxydopamine (6-OHDA) lesions unravel correlate vulnerability resilience. Together, this provides basis further studies neurophysiological role health disease.

Язык: Английский

---

Effects of APOE4 on omega-3 brain metabolism across the lifespan

Trends in Endocrinology and Metabolism, Год журнала: 2024, Номер 35(8), С. 745 - 757

Опубликована: Апрель 12, 2024

Язык: Английский

---

Sex, Body Mass Index, and APOE4 Increase Plasma Phospholipid–Eicosapentaenoic Acid Response During an ω-3 Fatty Acid Supplementation: A Secondary Analysis

Journal of Nutrition, Год журнала: 2024, Номер 154(5), С. 1561 - 1570

Опубликована: Март 19, 2024

The brain is concentrated with omega (ω)-3 (n-3) fatty acids (FAs), and these FAs must come from the plasma pool. 2 main ω-3 FAs, docosahexaenoic acid (DHA) eicosapentaenoic (EPA), be in form of nonesterified (NEFA) or esterified within phospholipids (PLs) to reach brain. We hypothesized that concentrations can modulated by sex, body mass index (BMI, kg/m2), age, presence apolipoprotein (APO) E-ε4 allele response supplementation. This secondary analysis aimed determine concentration EPA DHA PL NEFA after an FA a placebo supplementation investigate whether factors change supplement. A randomized, double-blind, placebo-controlled trial was conducted. Participants were randomly assigned either supplement (DHA 0.8 g 1.7 daily) for 6 mo. fasting samples extracted subsequently separated into PLs NEFAs using solid-phase extraction. as quantified gas chromatography. pool significantly increased 31%-71% 42%-82%, respectively, 1 mo No influenced responses In pool, 83%-109% 387%-463% APOE4 carriers, females, individuals BMI ≤25 had higher than noncarriers, males, those >25, respectively. are APOE4, BMI. These should considered when designing clinical trials involving registered at clinicaltrials.gov NCT01625195.

Язык: Английский

---

Myricanol improves metabolic profiles in dexamethasone induced lipid and protein metabolism disorders in mice

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 174, С. 116557 - 116557

Опубликована: Апрель 7, 2024

Myricanol (MY) is one of the main active components from bark Myrica Rubra. It demonstrated that MY rescues dexamethasone (DEX)-induced muscle dysfunction via activating silent information regulator 1 (SIRT1) and increasing adenosine 5'-monophosphate-activated protein kinase (AMPK) phosphorylation. Since SIRT1 AMPK are widely involved in metabolism nutrients, we speculated may exert beneficial effects on DEX-induced metabolic disorders. This study for first time applied targeted metabolomics to investigate glucose, lipids, abnormality mice. The results showed significantly reversed soleus gastrocnemius weight loss, fiber damage, strength loss. alleviated disorders by glucose transporter type 4 (GLUT4) expressions. Additionally, myricanol prevented cell apoptosis atrophy inhibiting caspase 3 cleavages ring-finger protein-1 (MuRF1) expression. Metabolomics treatment serum content carnitine ph-C1, palmitoleic acid, PS (16:0_17:0), PC (14:0_20:5), PE (P-18:1_16:1), Cer (t18:2/38:1(2OH)), four amino acids their metabolites, 16 glycerolipids DEX Kyoto encyclopedia genes genomes (KEGG) set enrichment analysis (MSEA) revealed mainly affected pathways, glycerolipid metabolism, lipolysis, fat digestion absorption, lipid atherosclerosis, cholesterol pathways through regulation metabolites glutathione, butanoate, vitamin B6, glycine, serine threonine, arachidonic riboflavin metabolism. Collectively, can be used as an attractive therapeutic agent abnormalities.

Язык: Английский

---

Liposomes as versatile agents for the management of traumatic and nontraumatic central nervous system disorders: drug stability, targeting efficiency, and safety

Neural Regeneration Research, Год журнала: 2024, Номер 20(7), С. 1883 - 1899

Опубликована: Июль 10, 2024

Various nanoparticle-based drug delivery systems for the treatment of neurological disorders have been widely studied. However, their inability to cross blood–brain barrier hampers clinical translation these therapeutic strategies. Liposomes are nanoparticles composed lipid bilayers, which can effectively encapsulate drugs and improve across into brain tissue through targeting permeability. Therefore, they potentially treat traumatic nontraumatic central nervous system diseases. In this review, we outlined common properties preparation methods liposomes, including thin-film hydration, reverse-phase evaporation, solvent injection techniques, detergent removal methods, microfluidics techniques. Afterwards, comprehensively discussed current applications liposomes in diseases, such as Alzheimer’s disease, Parkinson’s Huntington’s amyotrophic lateral sclerosis, injury, spinal cord tumors. Most studies related still laboratory stage not yet entered trials. Additionally, application practice faces challenges stability, efficiency, safety. proposed development strategies further promote disease research.

Язык: Английский

---