Banca de QUALIFICAÇÃO: NATHASHA MARIA CORREA PRADO LOPES

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
STUDENT : NATHASHA MARIA CORREA PRADO LOPES
DATE: 12/06/2025
TIME: 13:00
LOCAL: Plataforma Teams
TITLE:

Sexual Dimorphism and Age Modulate Behavior and Mitochondrial Bioenergetics in a Murine Model of Familial Hypercholesterolemia

KEY WORDS:

Familial hypercholesterolemia, sexual dimorphism, aging, metabolic dysfunction, cognition, mitochondria.

PAGES: 58
BIG AREA: Ciências Biológicas
AREA: Bioquímica
SUMMARY:

Familial hypercholesterolemia (FH) is a genetic dyslipidemia caused by functional impairment of the low-density lipoprotein receptor (LDLr), leading to disruptions in lipoprotein metabolism and accumulation of cholesterol in the bloodstream. Recent studies suggest that dyslipidemia may increase the risk of developing dementia, including Alzheimer’s disease, potentially through mechanisms involving chronic inflammation, oxidative stress, and impaired cerebral blood flow. Considering the influence of sex dimorphism and aging on metabolic and cogntive functions, this study used male and female wild-type (WT) and LDL receptor knockout (LDLr⁻/⁻) C57Bl/6 mice at 6 and 12 months of age. Animals underwent behavioral tests including Open Field (OF), Object Location (OL), and Elevated Plus Maze (EPM), to assess locomotor activity, spatial memory, and anxiety-like behavior, respectively. Blood samples were collected for lipid profile analysis, and hippocampal and brown adipose tissue (BAT) samples were dissected for mitochondrial function assessment using high-resolution respirometry. LDLr⁻/⁻ males and females showed significantly elevated total cholesterol and triglyceride levels compared to their WT counterparts. In the OF test, LDLr⁻/⁻ males displayed increased locomotion at both ages, while this effect was observed only in 12-month-old females. In the ORT, both male and female LDLr⁻/⁻ mice exhibited impaired spatial memory regardless of age. In the EPM, 12-month-old LDLr⁻/⁻ males showed a significant increase in open arm entries and total distance traveled at both ages, whereas no such effect was observed in females. BAT respirometry revealed reduced UCP-1 activity in 6-month-old LDLr⁻/⁻ males compared to agematched WT mice. In females, aging was a determining factor, with significantly reduced UCP-1 activity observed in older mice compared to younger counterparts of the same genotype. Hippocampal respirometry showed that 6-month-old LDLr⁻/⁻ males had significantly reduced oxygen (O₂) consumption related to complex I+II activity, oxidative phosphorylation (OXPHOS), and electron transport system (ETS) capacity—dysfunctions not observed at 12 months. Conversely, 12-month-old LDLr⁻/⁻ females showed significant reductions in O₂ consumption associated with complex I+II activity, OXPHOS, ETS, and ATP production.

COMMITTEE MEMBERS:
Externo à Instituição - EDUARDO LUIZ GASNHAR MOREIRA - UFSC
Externa ao Programa - 2329402 - ANGELICA AMORIM AMATO - nullInterno - 1316471 - DANIEL MENDES PEREIRA ARDISSON DE ARAUJO
Presidente - 2862542 - KELLY GRACE MAGALHAES