After 24-hour middle cerebral artery occlusion (MCAO) in spontaneously hypertensive rats, brain ceramide level increased from baseline reached 595% (ischemic core) and 460% (perifocal/penumbral areas); brain glucosylceramide synthase (GCS) activities in these areas simultaneously decreased by 70% and 50%, respectively. Ten-minute MCAO preconditioning significantly attenuated 24-hour MCAO-induced ceramide accumulation by 40% to 60% in ischemic core and perifocal areas, and GCS activities improved by 60% to 70% in both areas. Thus, potentially toxic levels of brain ceramide induced by MCAO were attenuated to intermediate levels in preconditioned animals; brain GCS activity was relatively preserved. In ischemic tolerance, GCS appears to modulate otherwise high levels of brain ceramide.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1097/01.WCB.0000119990.06999.A9 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Safe and Orally Bioavailable Inhibitor of Serine Palmitoyltransferase Improves Age-Related Sarcopenia.
ACS Pharmacol Transl Sci
January 2025
Laboratory of Integrative Systems Physiology, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne 1015, Switzerland.
The accumulation of ceramides and related metabolites has emerged as a pivotal mechanism contributing to the onset of age-related diseases. However, small molecule inhibitors targeting the ceramide synthesis pathway for clinical use are currently unavailable. We synthesized a safe and orally bioavailable inhibitor, termed ALT-007, targeting the rate-limiting enzyme of ceramide synthesis, serine palmitoyltransferase (SPT).
View Article and Find Full Text PDFImpaired lipid homeostasis and elevated lipid oxidation of erythrocyte membrane in adolescent depression.
Redox Biol
January 2025
Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, China; Shanghai Mental Health Center, Shanghai Key Laboratory of Psychiatry Disorders, Shanghai Jiao Tong University, Shanghai, China. Electronic address:
Adolescent depression is a globally concerned mental health issue, the pathophysiological mechanisms of which remain elusive. Membrane lipids play a crucial role in brain development and function, potentially serving as a crossroad for the abnormalities in neurotransmitters, neuroendocrine, inflammation, oxidative stress, and energy metabolism observed in depressed adolescents. The primary aim of this study was to investigate the erythrocyte membrane lipid profile in adolescent depression.
View Article and Find Full Text PDFCharacterisation of the Plasma and Faecal Metabolomes in Participants with Functional Gastrointestinal Disorders.
Int J Mol Sci
December 2024
The Riddet Institute, Massey University, Palmerston North 4474, New Zealand.
There is evidence of perturbed microbial and host processes in the gastrointestinal tract of individuals with functional gastrointestinal disorders (FGID) compared to healthy controls. The faecal metabolome provides insight into the metabolic processes localised to the intestinal tract, while the plasma metabolome highlights the overall perturbances of host and/or microbial responses. This study profiled the faecal ( = 221) and plasma ( = 206) metabolomes of individuals with functional constipation (FC), constipation-predominant irritable bowel syndrome (IBS-C), functional diarrhoea (FD), diarrhoea-predominant IBS (IBS-D) and healthy controls (identified using the Rome Criteria IV) using multimodal LC-MS technologies.
View Article and Find Full Text PDFTreadmill intervention attenuates motor deficit with 6-OHDA-induced Parkinson's disease rat via changes in lipid profiles in brain and muscle.
Aging (Albany NY)
January 2025
School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan.
One of the key hallmarks of Parkinson's disease is the disruption of lipid homeostasis in the brain, which plays a critical role in neuronal membrane integrity and function. Understanding how treadmill training impacts lipid restructuring and its subsequent influence on motor function could provide a basis for developing targeted non-pharmacological interventions for individuals living with early stage of PD. This study aims to investigate the effects of a treadmill training intervention on motor deficits induced by 6-OHDA in rats model of PD.
View Article and Find Full Text PDFIncreased α-synuclein phosphorylation and oligomerization and altered enzymes in plasma of patients with Parkinson's disease.
Neuroscience
December 2024
Department of Neurobiology and National Clinical Research Center for Geriatrics, Xuanwu Hospital of Capital Medical University, Beijing, China; Center of Parkinson's Disease, Beijing Institute for Brain Disorders, Beijing, China; Beijing Key Laboratory for Parkinson's Disease, Beijing, China. Electronic address:
The brain of patients with Parkinson's disease (PD) was characterized by increased phosphorylation and oligomerization of α-synuclein (α-syn) and altered activity of enzymes regulating α-syn phosphorylation and oligomerization. Whether increased α-syn phosphorylation and oligomerization as well as related enzyme changes can be detected in the plasma of PD patients remains unclear. Here, we showed that human α-syn proteins incubated in PD plasma formed more oligomerized α-syn (O-α-syn) and phosphorylated α-syn (pS-α-syn) than those in healthy control (HC) plasma.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!