We previously demonstrated that viral vector-mediated striatal Ca1.3 calcium channel downregulation in young adult (3mo) male parkinsonian rats provides uniform, robust protection against levodopa-induced dyskinesias (LID). Acknowledging the association of PD with aging and incidence in male and female sexes, we have expanded our studies to include rats of advancing age of both sexes. The current study directly contrasts age and sex, determining their impact on efficacy of intrastriatal AAV-Ca1.3-shRNA to prevent LID induction, removing the variable of levodopa-priming. Considering both sexes together, late-middle-aged ('aged'; 15mo) parkinsonian rats receiving AAV-Ca1.3-shRNA developed significantly less severe LID compared control AAV-scramble(SCR)-shRNA rats, however therapeutic benefit was significantly less robust than observed in young males. When considered separately, females showed significantly less therapeutic benefit than males. Furthermore, aged non-cycling/proestrous-negative female rats were refractory to LID induction, regardless of vector. This study provides novel insight into the impact of age and sex on the variable antidyskinetic responses of Ca1.3-targeted gene therapy, highlighting the importance of including clinically relevant age and sex populations in PD studies.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.neurobiolaging.2025.02.003 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Altered diversity and composition of gut microbiota in Korean children with food allergy.
Clin Transl Allergy
March 2025
Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
Background: This study aimed to comprehensively characterize the gut microbiome and identify individual and grouped gut microbes associated with food allergy (FA) using 16S rRNA gene sequencing.
Methods: Fecal samples were collected from children with IgE-mediated FA and from sex- and age-matched controls. The V3-V4 variable regions of the 16S rRNA gene of the gut microbiome were profiled using next-generation sequencing (Illumina, USA).
Fruit, vegetables and discretionary food intake in Australian adults: Past trends and predicted progress towards population preventive health targets for 2030.
Aust N Z J Public Health
February 2025
Commonwealth Scientific and Industrial Research Organisation (CSIRO) Health & Biosecurity, Adelaide, South Australia 5000, Australia. Electronic address:
Objective: In Australia, 'improving access to and the consumption of a healthy diet' is a focus in the National Preventive Health Strategy. The objective of this paper is to describe the past trends and future projections of population intakes against the Strategy's targets of increasing fruit consumption to 2 servings per day; increasing vegetables to 5 servings; and reducing discretionary foods to <20% of total energy by 2030.
Methods: Self-reported intake data were available from an online survey of 275,170 Australian adults collected between 2015 and 2023.
The incidence and cause of reoperation for complications after volar locking plate fixation of distal radial fractures.
J Orthop Sci
March 2025
Department of Orthopedics, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan; School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan. Electronic address:
Background: Distal radial fractures are the most common upper extremity fractures. Volar locking plate fixation has become the standard surgical treatment, providing stable angular fixation, early rehabilitation, and effective support for comminuted and osteopenic bones. This study aimed to analyze the incidence and causes of major complications requiring secondary surgeries following volar plating for distal radial fractures and to investigate the correlation between demographic factors and postoperative outcomes, including major complications and reoperation.
View Article and Find Full Text PDFOmega-3 index improves upon the pooled cohort equation in predicting risk for CVD.
J Clin Lipidol
February 2025
Fatty Acid Research Institute, Sioux Falls, SD, USA (Drs Tintle, Marchioli, and Harris); Department of Internal Medicine, Sanford School of Medicine, University of South Dakota, Sioux Falls, SD, USA (Dr Harris).
Background: Accurate predictive tools are crucial for identifying patients at increased risk for atherosclerotic cardiovascular disease (ASCVD). The Pooled Cohort Equation (PCE) is commonly used to predict 10-year risk for ASCVD, but its accuracy remains imperfect.
Objective: This study examined the extent to which the omega-3 index (O3I; the proportion of eicosapentaenoic acid+docosahexaenoic acid in erythrocyte membranes) improved the predictive capability of PCE.
Vitality is associated with systemic inflammation in cystic fibrosis adults on elexacaftor/tezacaftor/ivacaftor.
J Cyst Fibros
March 2025
Division of Respiratory Medicine, Department of Medicine, University of British Columbia, Vancouver, BC, Canada; Centre for Heart Lung Innovation, University of British Columbia, Vancouver, BC, Canada. Electronic address:
Fatigue is common among adults with cystic fibrosis (awCF) and may be associated with systemic inflammation. This study examines systemic inflammation, measured by C-reactive protein (CRP), and fatigue, assessed using the Cystic Fibrosis Questionnaire-Revised (CFQ-R) vitality domain, in individuals initiating elexacaftor/tezacaftor/ivacaftor (ETI) therapy. In a cohort of 61 awCF from St.
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!