Akademik Veri Yönetim Sistemi
36th Congress of the European-College-of-Neuropsychopharmacology (ECNP), Barcelona, İspanya, 7 - 10 Ekim 2023, cilt.2, ss.82
Bempedoic acid attenuates cognitive impairment and
depression-like behavior in middle-aged rats
G. Çelebi1, G.
Bugutekin1, S.S. Gocmez1, K Kavram Sarıhan2,
S Furat Rencber2, F. Ö. Halis1, M Cingöz1,
Ö Barış3, T Utkan1,4
1Kocaeli University, Faculty of Medicine, Department of
Pharmacology, Kocaeli Turkey 2Kocaeli University, Faculty of
Medicine, Department of Histology and Embryology, Kocaeli, Turkey.
3Kocaeli University, Faculty of Medicine, Department
of Cardiovascular Surgery, Kocaeli, Turkey,
4Kocaeli University, Experimental Medical Research and
Application Center, Kocaeli, Turkey.
Background:
It is known that normal aging leads to cognitive impairment and depressive
disorder. Recent clinical and experimental studies suggest that statins may
prove beneficial in management of depressive and cognitive disorders as
research shifts towards repurposing existing interventions. Bempedoic acid, an
ATP citrate lyase inhibitor, was recently approved for the treatment of
hypercholesterolemia as an LDL cholesterol lowering agent. Although statins
have been shown to improve cognitive function and depression-like behavior by
increasing levels of brain-derived neurotrophic factor (BDNF) in experimental
and clinical studies, there are no studies evaluating the effects of bempedoic
acid these parameters. Therefore, we investigated effects of chronic bempedoic
acid treatment on cognitive function and depression-like behavior associated
with biological aging.
Methods:
Thirty male rats were divided three subgroups (n=10 in each group): Young adult
control (4 month-old), middle-aged control (12 month-old), and bempedoic acid
(30 mg/kg/day, orally, for 30 days) treated middle-aged rats. At the end of
this period, total locomotor activity test (TLA), passive avoidance test (PAT)
and forced swimming test (FST) were measured. In the PAT, the retention latency
(RL) of animals was recorded on the second day of testing in order to evaluate
emotional learning and memory function. The modified FST performed to assess
despair-like behavior. The immobility time, linked to depressive-like behavior,
was recorded during the last 4 min of the 6-min testing period. The behavioral
tests were performed under controlled environmental conditions with the support
of video-tracking software (EthoVision XT10; Noldus Information Technology,
Wageningen, the Netherlands). The rats were sacrificed and brain hippocampal tissues
were collected for assessment of BDNF levels with immunohistochemical analysis.
Data are the mean±Standard error of the mean (SEM). The significance was conducted
with one-way ANOVA followed by a post hoc Tukey–Kramer test. The immunoreactivity
scores were compared by the Kruskal–Wallis test following Dunn’s multiple comparison
test; p<0.05 was considered significant.
Results: In
the PAT, middle-aged rats showed a significantly lower RL time compared to
young adult rats (p<0.05), indicated impaired retention of emotional memory
in this task. However, there was no difference between bempedoic acid-treated
middle-aged rats and young adult rats. In the FST, in terms of immobility time,
middle-aged rats exhibited more immobility than young adult control rats
(p<0.05). However, there was no difference between young adult control and middle-aged-treated
with bempedoic acid groups. Also, there was no significant difference between
four groups in terms of TLA. The levels of BDNF protein decreased in middle-aged
rats (p<0.05) and reversed to the young controls after bempedoic acid
treatment.
Conclusions:
Our results suggest that bempedoic acid prevents learning and memory deficits
and depression-like behavior in the biological aging rat model. The improvement
of neurotrophin levels after treatment may contribute these beneficial effects.
These findings will form the basis for further experimental and clinical
research on the effects of bempedoic acid on cognitive functions and depression-like
behavior in the during aging.
Key words:
Bempedoic acid, depression-like behavior, cognitive function, learning, memory