Page 35 - Q. Neuroscience

Inhibitory effect of carvacrol on
lipopolysaccharide-induced memory
impairment in rats

Bombi Lee , Insop Shim 1,2 , Hyejung Lee , and Dae-Hyun Hahm 1,2
1
1
Q20
1 Acupuncture & Meridian Science Research Center (AMSRC),
2 Department of Physiology, College of Medicine, Kyung Hee University, Seoul, 02447, Republic of Korea.
ABSTRACT RESULTS
Neuroinflammation is an important process underlying a wide variety of Behavioral test
neurodegenerative diseases. Carvacrol (CAR) is a phenolic monoterpene commonly used
as a food additive due to its antibacterial properties, but it has also been shown to A B C
exhibit strong antioxidative, anti-inflammatory, and neuroprotective effects. Here, we
sought to investigate the effects of CAR on inflammation in the hippocampus and
prefrontal cortex, as well as the molecular mechanisms underlying these effects. In our
study, lipopolysaccharide (LPS) was injected into the lateral ventricle of rats to induce
memory impairment and neuroinflammation. Daily administration of CAR (25, 50, and
100 mg/kg) for 21 days improved recognition, discrimination, and memory impairments
relative to untreated controls. CAR administration significantly attenuated expression of
several inflammatory factors in the brain, including interleukin-1β, tumor necrosis
factor-α, and cyclooxygenase-2. In addition, CAR significantly increased expression of
brain-derived neurotrophic factor (BDNF) mRNA, and decreased expression of Toll-like
receptor 4 (TLR4) mRNA. Taken together, these results show that CAR can improve Fig. 1. Effects of CAR administration on recognition memory was assessed using the novel ORT measuring the
memory impairment caused by neuroinflammation. This cognitive enhancement is due to time taken to sniff familiar and novel objects during a 3-min choice trial (A) and the ability to discriminate (B)
the anti-inflammatory effects of CAR medicated by its regulation of BDNF and TLR4. Thus, between familiar and novel objects. The OFT was used to assess the effect of EGCG on locomotor activity
CAR has significant potential as an inhibitor of memory degeneration in (counts) and total number of rearing bouts (C). ** p<0.01, *** p<0.001 vs. the SAL group, # p<0.05, ## p<0.01,
vs. the LPS group.
neurodegenerative diseases.
Keywords: Lipopolysaccharide, Memory, Inflammation, Carvacrol, Morris water maze A B
INTRODUCTION
• What is Alzheimer’s disease (AD)? C
- the most common form of dementia.
- included confusion, irritability and
aggression,
mood swings, trouble with language, and
long-term
memory loss.
- associated with plaques and tangles in the
brain.
- cholinergic hypothesis: caused by reduced
synthesis of the neurotransmitter Fig. 2. The MWM test was used to assess the effect of CAR on spatial learning and memory with time to escape
acetylcholine. (latency) from water during acquisition trials using a submerged platform (A), percentages of time spent in the
- amyloid hypothesis: amyloid beta (Aβ) target quadrant (B), and swimming speed (C) treated as outcome measures. * p<0.05, ** p<0.01 vs. the SAL
group, # p<0.05, ## p<0.01 vs. the LPS group.
deposits are
the fundamental cause of the disease.
• How dose neuroinflammation lead to
memory impairment?
- neuroinflammation isorders with sustained
increase in various pro-inflammatory
cytokines, such as tumor necrosis factor-α
(TNF-α) and interleukin-1β (IL-1β), in the
central nervous system are closely correlated
with the cognitive dysfunction primarily
associated with progression of AD
pathogenesis.
• How effective is carvacrol for memory
impairment?
- a phenolic monoterpene found in abundance in the
essential oils of Lamiaceae plant species. Fig. 3. Effects of CAR on IL-1β, IL-6, TNF-α, COX-2, and NF-κB concentrations in the hippocampus and
- recovery from fatigue, to enhance resistance prefrontral cortex of rats exposed to LPS (n=6/group). * p<0.05, ** p<0.01 vs. SAL group; # p<0.05,
## p<0.01 vs. LPS group.
capabilities against various psychosomatic
disorders.
- various benefits against stress and to strengthen
the immune system.
METHODS
Experimental grouping & procedure Fig. 4. Effects of CAR on the expression of iNOS, TLR4, and BDNF mRNAs in rats with LPS-induced
hippocampal impairment. The expression levels of iNOS, TLR4, and BDNF mRNAs were normalized to GAPDH
Morris Water maze test(MWM) mRNA as an internal control (n=6/group). * p<0.05 and ** p<0.01 vs. SAL group; # p<0.05 vs. LPS group.
CONCLUSIONS
Object-recognition test(ORT) 1. In present results indicate the hypothesis that CAR ameliorated LPS-
stimulated memory and behavioral deficits in rats.
2. Administration of CAR significantly weakened the problems of LPS-
stimulated damage significantly, as suggested by ameliorated cognitive
ability and object recognition memory during behavioral tests, prevented
decreases in BDNF levels, and normalization of the HPA axis
dysregulation. CAR also inhibited LPS-simulated alternation of pro-
inflammatory cytokines such as IL-1β and TNF-α in the hippocampus.
3. Taken together, the data presented here suggest that CAR
administration significantly attenuated LPS-induced defects in cognitive
function via the attenuation of neuroinflammation through its effects on
TLR4 and BDNF. These findings suggest that CAR may be useful for the
treatment of psychologically rooted behaviors and neurochemical
Open field test(OFT) alterations seen in memory impairment.
4. Our results suggest that CAR may have efficacy as a functional food
good material for amelioration of object recognition memory,
improvement of learning and memory, and prevention of neuronal
modulations related to AD.
This research was supported by a grant of the National Research Foundation of Korea funded by the Korean
government (MEST)(2016R1D1A1A09917012), Republic of Korea.