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Effect of Royal Jelly on spatial learning and memory in rat model of streptozotocin-induced sporadic Alzheimer's disease

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It has been recently demonstrated that Royal jelly (RJ) has a beneficial role on neural functions. Alzheimer's disease (AD) is associated with impairments of learning and memory. Therefore, the present study was designed to examine the effect of RJ on spatial learning and memory in rats after intracerebroventricular injection of streptozotocin (icv-STZ). Rats were infused bilaterally with an icv injection of STZ, while sham rats received vehicle only. The rats were feed with RJ-contained food (3% w/w) (lyophilized RJ mixed with powdered regular food) or regular food for 10 days. Then spatial learning and memory was tested in the rats by Morris water maze test. Results showed that in icv-STZ group latency and path length were increased as compared to sham group, also icv-STZ rats less remembered the target quadrant that previously the platform was located; however, these were protected significantly in STZ group that received RJ-containing food. Our findings support the potential neuroprotective role of RJ and its helpful effects in AD.
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Advanced Biomedical Research | April - June 2012 | Vol 1 | Issue 2 1
Background: It has been recently demonstrated that Royal jelly (RJ) has a beneficial role on neural functions.
Alzheimer’s disease (AD) is associated with impairments of learning and memory. Therefore, the present study
was designed to examine the effect of RJ on spatial learning and memory in rats after intracerebroventricular
injection of streptozotocin (icv-STZ).
Materials and Methods: Rats were infused bilaterally with an icv injection of STZ, while sham rats received
vehicle only. The rats were feed with RJ-contained food (3% w/w) (lyophilized RJ mixed with powdered
regular food) or regular food for 10 days. Then spatial learning and memory was tested in the rats by
Morris water maze test.
Results: Results showed that in icv-STZ group latency and path length were increased as compared to
sham group, also icv-STZ rats less remembered the target quadrant that previously the platform was
located; however, these were protected significantly in STZ group that received RJ-containing food.
Conclusions: Our findings support the potential neuroprotective role of RJ and its helpful effects in AD.
Key words: Alzheimer’s disease, rat, Royal jelly, spatial learning and memory, streptozotocin
Address for correspondence:
Dr. Parham Reisi, Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran. E‑mail: p_reisi@med.mui.ac.ir
Received: 18‑01‑2012, Accepted: 13‑03‑2012
Abstract
Effect of Royal Jelly on spatial learning and memory in
rat model of streptozotocin‑induced sporadic Alzheimer’s
disease
Zohre Zamani, Parham Reisi1, Hojjatallah Alaei2, Ali Asghar Pilehvarian3
Applied Physiology Research Center, 1Department of Physiology, School of Medicine and Biosensor Research Center, 2Department of
Physiology, School of Medicine Isfahan University of Medical Sciences, 3Department of Basic Sciences,
Isfahan Payame Noor University, Isfahan, Iran
Original Article
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Website:
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DOI:
10.4103/2277-9175.98150
ABR_24_12R9
INTRODUCTION
Alzheimer’s disease (AD) is a disorder with a deadly
outcome and unknown etiology in human that aficted
many people worldwide.[1] This disease is characterized
Copyright: © 2012 Zamani. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction
in any medium, provided the original author and source are credited.
How to cite this article: Zamani Z, Reisi P, Alaei H, Pilehvarian AA. Effect of Royal Jelly on spatial learning and memory in rat model of streptozotocin-induced
sporadic Alzheimer's disease. Adv Biomed Res 2012;1:26.
by a progressive and irreversible neurodegeneration in
various brain regions, especially in the hippocampus,
which is an important area for memory and cognition.[2,3]
The increased production and accumulation of amyloid‑β
peptide (Aβ) contribute to progressive neuronal
degeneration.[4,5] Therefore, Alzheimer’s is associated
with decits in cognitive abilities such as learning
and memory in human beings.[5] Currently, there isn’t
any conclusive treatment for AD and the common
treatments just slow the progression of the disease and
manage some of the symptoms.[3]
Royal jelly (RJ) is an essential food for the honey
bee young larva and the queen herself, it thought to
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Zamani, et al.: Effects of Royal jelly on spatial learning and memory in Alzheimer's rat
2 Advanced Biomedical Research | April - June 2012 | Vol 1 | Issue 2
play important nutritional roles in the queen.[6] It is
a viscous substance secreted by the hypopharyngeal
and mandibular glands of the worker honey bee of the
species, Apis mellifera. It has been reported to have a
variety of biological activities toward various types of
cells and tissues of animal models.[6]
RJ is composed of proteins, carbohydrates, lipids
(including sterols and fatty acids), and traces of
mineral salts and vitamins.[7] This material has been
determined to exhibit a variety of pharmacological
activities including antitumor, antimicrobial,
vasodilative, and hypotensive activities, as well
as growth stimulating and infection preventing,
antihypercholesterolemic and anti‑inflammatory
activities. Several studies have been shown the
antioxidant activity of RJ.[8] For these reasons, for
more than 30 years, RJ has been used commercially
in medical products, healthy foods, and cosmetics, to
a wide extent.[8]
In addition, RJ facilitates the differentiation of all
types of brain cells including neurons from cultured
neural stem/progenitorcells (NS/NPCs).[6] RJ or its
components would facilitate in vivo neurogenesis
in the hippocampal dentate gyrus (DG).[9] However,
there are no reports so far showing the effects of RJ
on cognition behaviorally, especially when there is a
background of neurodegenerative disease.
One of the relevant animal models of Alzheimer’s
disease is intracerebroventricular streptozotocin
(icv‑STZ) injection.[1,10] Streptozotocin is a diabetogenic
drug that used to induce diabetes mellitus,[11] and recent
evidence suggests that the intracerebroventricular
(icv) injection of streptozotocin (STZ) to rats in a
subdiabetogenic dose causes prolonged impairment
of memory and brain metabolic process, as a sporadic
dementia of the Alzheimer’s type (SDAT) that
comprises more than 90% of Alzheimer’s patients in
the world.[1,10] Therefore, the aim of this study was
to evaluate the effect of RJ on learning and memory
in rats after intracerebroventricular injection of
streptozotocin (icv ‑STZ).
MATERIALS AND METHODS
Male Wistar rats (320 ± 20 g) were housed four per
cage and maintained on a 12 h light–dark cycle in an
air‑conditioned constant temperature (23 ± 1°C) room,
with food and water made available ad libitum. The
Ethic Committee for Animal Experiments at Isfahan
University approved the study and all experiments were
conducted in accordance with the National Institute
of Health Guide for the Care and Use of Laboratory
Animals (NIH Publications No. 80‑23) revised 1996.
Animals were divided into four groups (n = 9). The
rst group was the sham control (sham group), the
second group consisted of sham animals receiving
RJ‑contained food (sham‑RJ group), the third group
was the ICV‑STZ control (lesion group), and the
fourth group consisted of ICV‑STZ animals receiving
RJ‑contained food (lesion‑RJ). Rats in the control
groups received regular food.
Five days after surgical procedure, for recovery, rats
received RJ‑contained food for 10 days and then spatial
learning and memory was tested in the rats by Morris
water maze test.
RJ was administrated in the form of a mixed food
prepared by adding freeze‑dried RJ at 3% (w/w) in
regular food powder. The mixture and pure regular
food were made into pellets with a small amount of
water and desiccated under vacuum overnight.[9,12]
Surgical procedure
The rats were anesthetized with chloral hydrates
(400 mg/kg, i.p.) and their heads were fixed in
a stereotaxic frame. A heating pad was used
to maintain body temperature at 36.5 ± 0.5°C.
The skull was exposed and two small holes were
drilled and injection canula was lowered into the
lateral ventricles (anterior‑posterior = ‑0.8 mm;
medial‑lateral = ±1.6 mm; and dorsal‑ventral =
‑4.2 mm with reference to bregma).[13] Injection
canula was connected to a Hamilton syringe attached
to a microinjector unit. The lesion group received
a bilateral ICV injection of STZ (1.5 mg/kg in 4 µl
per site) as in previous studies.[10] The sham group
underwent the same surgical procedures, but the same
volume of saline was injected instead of STZ.
Morris water maze test
The circular tank (180 cm in diameter) was lled with
water (22 ± 2°C) made opaque and was surrounded by
a variety of extra‑maze cues. The tank was divided into
four quadrants and four start positions were located at
the interactions of the quadrants. Data were recorded
using custom software (Radiab 1). Twenty‑four hours
before water maze testing, all rats were habituated to
the water and apparatus.
In the spatial acquisition phase, the rats learned to
nd a submerged platform using extra‑maze cues.
A transparent Lucite platform (10 × 10 cm) was
submerged 2 cm underneath the water in north‑east
quadrant of the tank, where it remained for all spatial
trials [Figure 1a]. Each rat participated in 16 trials,
which were organized into daily block of four trials
(1 trial/start position within a block) for 4 consecutive
days. For each trial, the rat was given a maximum time
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Zamani, et al.: Effects of Royal jelly on spatial learning and memory in Alzheimer's rat
Advanced Biomedical Research | April - June 2012 | Vol 1 | Issue 2 3
of 60 s to locate the platform, after which it remained
there for 30 s. If the rat did not locate the platform
within 60 s, it was guided to it by the experimenter.
The next trial started immediately after removal from
the platform. Escape latencies (s), swim distance (cm),
and swim speed (cm/s) were recorded.
In the retention phase, 1 day and 1 week after
the spatial acquisition phase, 60‑s probe trial was
conducted to examine how well the rats had learned
the exact location of the platform. During this trial, the
platform was removed from the tank. The quadrant
time (percent time spent in the training quadrant)
was recorded during the probe trial.[14] To test possible
decits in sensory–motor processes, rats were tested
in the water maze with a visible platform on a new
location on the nal day of training.[15]
Statistical analysis
Data were analyzed using the SPSS 16 for Windows.
Results are given as mean ± S.E.M. The escape
latencies, path length, and swim speed were analyzed
with three‑factor mixed ANOVA for between‑subjects
differences between sham and lesion (“ICV‑STZ”
effect), between non‑RJ and RJ (“RJ” effect), and
ICV‑STZ*RJ effect interaction and repeated measures
(within subjects) effects across block interval 1 to 4
(“BLOCK” effect). The probe trial data for percentage
of time spent in each of the four zones were analyzed
by multivariate ANOVA.
RESULTS
All rats except lesion group showed a reduction in
escape latencies (BLOCK effect, F(3,96) = 46.157,
P < 0.001) and a reduction in the distance swam to
locate the platform (BLOCK effect, F(3,96)=25.259,
P < 0.001) across blocks of trials, indicating spatial
acquisition. Sham groups found the platform more
quickly than lesion groups [28.9 ±1.8 s and 43.54 ± 1.6 s,
respectively; ICV‑STZ effect, F(1,32) = 36.265,
P < 0.001] and took shorter paths to the platform
[637.7 ± 48.1 cm and 958.6 ± 43.6 cm, respectively;
ICV‑STZ effect, F(1,32) = 24.46, P < 0.001]. The rats
that received RJ contained food, found the platform
more quickly than the rats that received regular food
[30.48 ± 1.85 s and 41.94 ± 1.58 s, respectively; RJ
effect, F(1,32) = 22.2, P < 0.001] and took shorter paths
to the platform [687.4 ± 49.4 cm and 908.86 ± 42.9 cm,
respectively; RJ effect, F(1,32) = 11.65, P <0.01]. Also,
RJ contained food maintained both the escape latencies
[ICV‑STZ*RJ effect interaction, F(1,32) = 0.22,
P = 0.64] and the pathlengths [ICV‑STZ*RJ effect
interaction, F(1,32) = 0.06, P = 8] in lesion rats
[Figures 1b and 1c].
Swim speed did not show any change during
continuous day [BLOCK effect, F(3,96) = 2.01,
P = 0.118] and there wasn’t any difference between
the groups [Figure 1d].
Results from the probe trial as measured by the
mean percentage (%) time spent in each of the four
zones indicated that 1 day after acquisition phase the
sham groups spent more time in zone 1, where the
platform was previously located, than the ICV‑STZ
groups [38.14 ± 2.58% and 23.41 ± 2.33%, respectively;
ICV‑STZ effect, F(1,32) = 31.02, P < 0.001]. The
mean percentage (%) time spent in zone 1 was not
signicantly different between the rats that received
RJ‑contained food and the rats that received regular
food [36.71 ± 2.65% and 24.83 ± 2.26%, respectively;
RJ effect, F(1,32) = 3.564, P = 0.068]; however,
RJ‑contained food maintained that in lesion rats
[ICV‑STZ*RJ effect interaction, F(1,32) = 0.85,
P = 0.36] [Figure 2a].
One week after acquisition phase, the sham groups
spent more time in zone 1 than the ICV‑STZ groups
[38.19 ± 2.05% and 22.78 ± 1.86%, respectively;
ICV‑STZ effect, F(1,32) = 17.94, P < 0.001]. The rats
that received RJ‑contained food spent more time
in zone 1 than the rats that received regular food
[33.1 ± 2.1% and 27.87 ± 1.8%, respectively; RJ effect,
F(1,32) = 11.67, P < 0.01]; also, RJ‑contained food
maintained that in lesion rats [ICV‑STZ*RJ effect
interaction, F(1,32) = 0, P = 0.99) [Figure 2b].
DISCUSSION
The present results showed that use of RJ is effective
in signicant improvement of learning and memory
defects that induced with icv‑STZ in rats.
Like previous studies, our results demonstrated that
ICV‑STZ causes impairment of learning and memory in
rats.[16] The study has been shown that the application
of STZ in a subdiabetogenic dose in rats brain leads to
damage to glucose’s metabolism and causes reduction in
adenosine triphosphate (ATP/ADP ratio). This may be
calculated by the imbalance between intake and output
of energy.[17] It has been shown that acetylcholine is
necessary to formation and improvement of memory;
its synthesis needs to glucose metabolism and insulin
in order to control choline acetyltransferase (ChAT)
activity.[1] Previous researches have demonstrated that
icv‑STZ causes reduced energy metabolism/oxidative
stress leading to cognitive dysfunction by inhibiting the
synthesis of acetyl‑CoA and therefore acetyl‑choline
synthesis. Also, streptozotocin causes reduced ChAT
activity in hippocampus and increased cholinesterase
(ChE) activity in the rat’s brains.[1]
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Zamani, et al.: Effects of Royal jelly on spatial learning and memory in Alzheimer's rat
4 Advanced Biomedical Research | April - June 2012 | Vol 1 | Issue 2
In addition, like in AD, icv‑STZ through prolonged
impairment of brain energy metabolism and oxidative
damage increases the inammatory cytokines, such
as interleukin‑8 (IL‑8) and interleukin‑1 (IL‑1). This
inammatory cytokines and severe oxidative stress
lead to mitochondrial dysfunction and increase the
risk of cell apoptosis in the brain, particularly in the
hippocampus.[18,19]
As a secondary observation, our results demonstrated
that use of RJ in rats enhanced learning and
memory performance. Previous studies showed that
RJ stimulates production of neurotrophic factors,
such as glial cell line‑derived neurotrophic factor
(GDNF), and has neuroprotective effects in the adult
brain, especially in hippocampus.[6] These studies
are compatible with the results from our behavioral
study.
One of unique components in RJ is 10‑hydroxy‑
trans‑2decanoic acid (HDEA), an unsaturated fatty
acid. Because HDEA is a small unsaturated fatty
Figure 1: Effects of Royal jelly (RJ) contained food on performance during the spatial acquisition of Morris water maze test in rats with
intracerebroventricular injection of streptozotocin. Schematic diagram of tank and site of the platform (a). The escape latencies (b), the path length
(c), and the swim speed (d) at different days to reach the platform. Each point represents the day mean ± SEM of 4 swims. For latency and path
length, lower numbers indicate better performance (*P < 0.05 and **P < 0.01 with respect to the sham group, †P < 0.05 signicant difference
between the lesion and the lesion-RJ groups; n = 9).
d
c
b
a
Figure 2: Effects of Royal jelly (RJ) contained food on performance during the probe trial in rats with intracerebroventricular injection of
streptozotocin, quadrant time, as measured by mean percentage (%) time spent in each of the four zones, 1 day (a) and 1 week (b) after spatial
acquisition phase. Zone 1 was the training quadrant that previously platform was located (*P < 0.05 and **P < 0.01 with respect to the sham
group, †P < 0.05 signicantly difference between the lesion and the lesion-RJ groups; n = 9).
b
a
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Zamani, et al.: Effects of Royal jelly on spatial learning and memory in Alzheimer's rat
Advanced Biomedical Research | April - June 2012 | Vol 1 | Issue 2 5
acid, it can pass through blood–brain barrier. It has
been demonstrated that HDEA mimics the effects
of brain‑derived neurotrophic factor (BDNF) and
probably stimulate neurogenesis in the mature
brain.[20] Other active component in RJ is adenosine
monophosphate (AMP) N1‑oxide that is effective in
neuronal differentiation of PC12 cells.[7,20]
One of the factors which play an effective role in
pathogenesis of ageing and neurodegenerative
diseases is oxidative stress, which is an imbalance
between free radicals and antioxidant system.[21,22]
Oxygenate radicals can attack to proteins, nucleic
acids, and lipid membranes and accordingly interrupt
the integrity and performance of the cell.[23] The
brain tissue contains a lot of unsaturated fatty acids
which are especially vulnerable for free‑radical
attacks.[24] Therefore, antioxidant substances can
play an important role in prevention and cure of
neurodegenerative diseases.[10,16] Recently, studies
have suggested that RJ has free‑radical scavenging
capacity and is a highly efcient antioxidant.[25,26] RJ
has been shown that inhibits lipid proxidation both
in vitro and in vivo.[27]
RJ has a potent ability to improve insulin resistance
and this is a valuable effect in AD.[28] Same to AD or
ageing brain, ICV‑STZ in rats causes desensitization
of insulin receptors[29] and it has demonstrated
that ICV‑STZ through damage of the neuronal
insulin receptor induces progressive deteriorations
in the mental capacities of learning, memory, and
cognition.[1]
In conclusion, our ndings show that RJ protects
spatial learning and memory performance in AD and it
has positive effects on neural functions and cognition.
ACKNOWLEDGMENTS
This research was supported by the Applied Physiology
Research Center of Isfahan University of Medical Sciences,
Isfahan, Iran. Also, the authors wish to thank Isfahanhoney.
com Corporation for preparation and standardization of
royal jelly.
REFERENCES
1. Lannert H, Hoyer S. Intracerebroventricular administration of streptozotocin
causes long‑term diminutions in learning and memory abilities and in cerebral
energy metabolism in adult rats. Behav Neurosci 1998;112:1199‑208.
2. Herring A, Ambree O, Tomm M, Habermann H, Sachser N, Paulus W, et al.
Environmental enrichment enhances cellular plasticity in transgenic mice
with Alzheimer‑like pathology. Exp Neurol 2009;216:184‑92.
3. Robert R, Dolezal O, Waddington L, Hattarki MK, Cappai R, Masters CL,
et al. Engineered antibody intervention strategies for Alzheimer’s disease
and related dementias by targeting amyloid and toxic oligomers. Protein
Eng Des Sel 2009;22:199‑208.
4. Bothwell M, Giniger E. Alzheimer’s disease: Neurodevelopment converges
with neurodegeneration. Cell 2000;102:271‑3.
5. Smith JP, Lal V, Bowser D, Cappai R, Masters CL, Ciccotosto GD. Stimulus
pattern dependence of the Alzheimer’s disease amyloid‑beta 42 peptide’s
inhibition of long term potentiation in mouse hippocampal slices. Brain Res
2009;1269:176‑84.
6. Hashimoto M, Kanda M, Ikeno K, Hayashi Y, Nakamura T, Ogawa Y,
et al. Oral administration of royal jelly facilitates mRNA expression of
glial cell line‑derived neurotrophic factor and neurolament H in the
hippocampus of the adult mouse brain. Biosci Biotechnol Biochem 2005;
69:800‑5.
7. Hattori N, Nomoto H, Fukumitsu H, Mishima S, Furukawa S. Royal
jelly‑induced neurite outgrowth from rat pheochromocytoma PC12
cells requires integrin signal independent of activation of extracellular
signal‑regulated kinases. Biomed Res 2007;28:139‑46.
8. Kanbur M, Eraslan G, Silici S, Karabacak M. Effects of sodium uoride
exposure on some biochemical parameters in mice: Evaluation of the
ameliorative effect of royal jelly applications on these parameters. Food
Chem Toxicol 2009;47:1184‑9.
9. Hattori N, Ohta S, Sakamoto T, Mishima S, Furukawa S. Royal jelly facilitates
restoration of the cognitive ability in trimethyltin‑intoxicated mice. Evid Based
Complement Alternat Med 2009 doi:10.1093/ecam/nep029.
10. Ishrat T, Khan MB, Hoda MN, Yousuf S, Ahmad M, Ansari MA,
et al. Coenzyme Q10 modulates cognitive impairment against
intracerebroventricular injection of streptozotocin in rats. Behav Brain Res
2006;171:9‑16.
11. Reisi P, Babri S, Alaei H, Shari MR, Mohaddes G, Noorbakhsh SM,
et al. Treadmill running improves long‑term potentiation (LTP) defects in
streptozotocin‑induced diabetes at dentate gyrus in rats. Pathophysiology
2010;17:33‑8.
12. Narita Y, Nomura J, Ohta S, Inoh Y, Suzuki KM, Araki Y, et al. Royal jelly
stimulates bone formation: Physiologic and nutrigenomic studies with mice
and cell lines. Biosci Biotechnol Biochem 2006;70:2508‑14.
13. Paxinos G, Watson C. The rat brain in stereotaxic coordinates. 5th ed. San
Diego: Academic Press; 2005.
14. Hoveida R, Alaei H, Oryan S, Parivar K, Reisi P. Treadmill running improves
spatial memory in an animal model of Alzheimer’s disease. Behav Brain
Res 2011;216:270‑4.
15. Reisi P, Alaei H, Babri S, Shari MR, Mohaddes G. Effects of treadmill
running on spatial learning and memory in streptozotocin‑induced diabetic
rats. Neurosci Lett 2009;455:79‑83.
16. Ishrat T, Parveen K, Khan MM, Khuwaja G, Khan MB, Yousuf S, et al.
Selenium prevents cognitive decline and oxidative damage in rat model of
streptozotocin‑induced experimental dementia of Alzheimer’s type. Brain
Res 2009;1281:117‑27.
17. Zhou Y, Qu ZQ, Zeng YS, Lin YK, Li Y, Chung P, et al. Neuroprotective effect
of preadministration with Ganoderma lucidum spore on rat hippocampus.
Exp Toxicol Pathol 2011 Article in press.
18. Vendramini AA, de Labio RW, Rasmussen LT, Dos Reis NM, Minett T,
Bertolucci PH, et al. Interleukin‑8‑251T > A, Interleukin‑1alpha‑889C > T
and Apolipoprotein E polymorphisms in Alzheimer’s disease. Genet Mol
Biol 2011;34:1‑5.
19. Wiese L, Hempel C, Penkowa M, Kirkby N, Kurtzhals JA. Recombinant
human erythropoietin increases survival and reduces neuronal apoptosis
in a murine model of cerebral malaria. Malar J 2008;7:3.
20. Hattori N, Nomoto H, Fukumitsu H, Mishima S, Furukawa S. Royal jelly and its
unique fatty acid, 10‑hydroxy‑trans‑2‑decenoic acid, promote neurogenesis
by neural stem/progenitor cells in vitro. Biomed Res 2007;28:261‑6.
21. Holscher C, Gengler S, Gault VA, Harriott P, Mallot HA. Soluble
beta‑amyloid[25‑35] reversibly impairs hippocampal synaptic plasticity and
spatial learning. Eur J Pharmacol 2007;561:85‑90.
22. Sharma M, Gupta YK. Intracerebroventricular injection of streptozotocin in
rats produces both oxidative stress in the brain and cognitive impairment.
Life Sci 2001;68:1021‑9.
23. Aksenov MY, Aksenova MV, Buttereld DA, Geddes JW, Markesbery WR. Protein
[Downloaded free from http://www.advbiores.net on Wednesday, September 28, 2016, IP: 95.90.240.75]
Zamani, et al.: Effects of Royal jelly on spatial learning and memory in Alzheimer's rat
6 Advanced Biomedical Research | April - June 2012 | Vol 1 | Issue 2
oxidation in the brain in Alzheimer’s disease. Neuroscience 2001;103:373‑83.
24. Gutteridge JM. Lipid peroxidation and antioxidants as biomarkers of tissue
damage. Clin Chem 1995;41:1819‑28.
25. El‑Nekeety AA, El‑Kholy W, Abbas NF, Ebaid A, Amra HA, bdel‑Wahhab MA.
Efcacy of royal jelly against the oxidative stress of fumonisin in rats. Toxicon
2007;50:256‑69.
26. Jamnik P, Goranovic D, Raspor P. Antioxidative action of royal jelly in the
yeast cell. Exp Gerontol 2007;42:594‑600.
27. Guo H, Ekusa A, Iwai K, Yonekura M, Takahata Y, Morimatsu F. Royal jelly
peptides inhibit lipid peroxidation in vitro and in vivo. J Nutr Sci Vitaminol Source of Support: Nil, Conict of Interest: None declared.
2008;54:191‑5.
28. Zamami Y, Takatori S, Goda M, Koyama T, Iwatani Y, Jin X, et al. Royal
jelly ameliorates insulin resistance in fructose‑drinking rats. Biol Pharm Bull
2008;31:2103‑7.
29. Kaur B, Singh N, Jaggi AS. Exploring mechanism of pioglitazone‑induced
memory restorative effect in experimental dementia. Fundam Clin
Pharmacol 2009;23:557‑66.
[Downloaded free from http://www.advbiores.net on Wednesday, September 28, 2016, IP: 95.90.240.75]
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... Therefore, it is commonly used as a supplement for diseases such as cancer, diabetes, and cardiovascular dementia, and royal jelly has shown significant neuroprotective actions [6]. It has been demonstrated that royal jelly has a beneficial role in neural functions and was investigated on spatial learning and memory in a rat model of streptozotocininduced sporadic Alzheimer's disease [7]. Moreover, royal jelly long-term administration can affect the brain neurotransmitters in naturally aged rats [8]. ...
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... Alzheimer disease (AD) has complex causes, including nerve fiber tangles, amyloid beta deposition, inflammatory response, and oxidative stress response. In many animal experiments at home and abroad and in vitro cell experiments, it has been proved that royal jelly can improve the spatial learning and memory ability of AD model rats [30] by effectively alleviating the toxicity of β-amyloid in AD and significantly reducing β-amyloid species [31]. However, whether royal jelly and its functional components have a positive effect on the prevention and delaying of human AD and their possible mechanism of action remain to be further studied. ...
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Background Beekeeping and honey gathering are traditional forms of agricultural farming in China. However, only few studies have focused on the nutritional status and health level of this special occupational group. Objective By comparing the health status of apiculturists (beekeepers) and vegetable farmers in plain areas of Hubei Province, and analyzing the influence of dietary structure and intake on their nutritional level, this paper provides a scientific theoretical basis for the further development of health education and disease prevention for beekeepers. Methods From February to April 2016, 191/236 beekeepers (80.9% of the total beekeepers) with large-scale breeding (300-500 colonies) and 182 vegetable farmers in the same area were sampled by the cluster sampling method. Their nutrient composition was analyzed using a human body composition analyzer, dietary structure information was collected using the dietary frequency query method, and cognitive function was investigated. In addition, blood samples of both groups were collected. ResultsA total of 362 valid questionnaires (beekeepers/vegetable farmers: 185/177) were collected, with an effective response rate of 97.1% (362/373). Both beekeepers and vegetable farmers were overweight, and the beekeepers’ grip strength was much stronger than that of the vegetable farmers’ regardless of gender. The dietary structure of beekeepers is very unique: 29.7% (55/185) of beekeepers indicated consuming royal jelly regularly for more than 10 years. Their main foods are grain, cereals, and fresh vegetables; 68.1% (126/185) of the beekeepers never drank milk and other dairy products, and their overall nutrient intake is unbalanced. The average intake of cellulose in this group was also significantly higher than that in the epidemiological survey in the same sex and age group. The intake of vitamin A and selenium in the beekeepers group was significantly higher than that in the vegetable-farmers group (all P
... Previous studies have shown that RJ consumption increased memory, learning and neurotrophins as well as decreased beta amyloid depletion in mouse (8); RJ consumption modulated serotonin and dopamine in the cortex tissue of the elderly rats, however, this effect was dose dependent, so that 100 mg/kg RJ had favorable effects than 50 mg/kg RJ (9). Also, RJ increased neuronal function, memory, and learning in an animal model of AD (10). Given the role of serotonin and dopamine as important neurotransmitters in the central nervous system and their role in the plasticity of hippocampal neurons, it seems that the use of noninvasive and non-pharmacological approaches may be an appropriate strategy to improve cognitive function in patients with AD. ...
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The aim of this study was to investigate if preadministration with Ganoderma lucidum spore (GLS) could (1) alleviate oxidative stress and mitochondrial dysfunction in rat hippocampus of intracerebroventricular (ICV) injection of streptozotocin (STZ), (2) protect neurons from apoptosis, and (3) improve cognitive dysfunction. Three groups of Sprague-Dawley rats were preadministrated with GLS at doses of 2.0, 4.0 and 8.0g/kg, respectively, for 3 weeks before the ICV STZ injury. Thereafter the rats were operated with ICV STZ (1.5mg/kg) bilaterally on days 1 and 3. The behavioral alterations, oxidative stress indexes, ATP, cytochrome oxidase (CytOx), and histopathology of hippocampal neurons were studied. The results showed that ICV STZ model rats exhibited a significant increase of malondialdehyde (MDA), a significant decrease of glutathione reductase (GR), reduced glutathione (GSH), ATP and CytOx, accompanied with marked impairments in spatial learning and memory, and severe damage of hippocampal neuron. In conclusion, preadministration with GLS at dose of 8.0g/kg in ICV STZ rats significantly reversed these abnormalities. In conclusion, preadministration with GLS might protect hippocampus from oxidative impairment and energy metabolism disturbance of ICV STZ. This may also provide useful information for future research on the pathogenesis and prevention of Alzheimer's disease (AD).
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Alzheimer's disease (AD) is a progressive neurodegenerative disease that is characterized by a decline in cognitive function and severe neuronal loss in the cerebral cortex and certain subcortical regions of the brain including nucleus basalis magnocellularis (NBM) that play an important role in learning and memory. There are few therapeutic regimens that influence the underlying pathogenic phenotypes of AD, however, of the currently available therapies, exercise training is considered to be one of the best strategies for attenuating the pathological phenotypes of AD for people with AD. Here, we sought to investigate the effect of treadmill running on spatial memory in Alzheimer-induced rats. Male Wistar rats were split into two groups namely shams (n=7) and lesions with the lesion group subdivided further into the lesion-rest (n=7) and lesion-exercise (n=7). The lesion-exercise and shams were subjected to treadmill running at 17 meters per minute (m/min) for 60 min per day (min/day), 7 days per week (days/wk), for 60 days. Spatial memory was investigated using the Morris Water Maze test in the rats after 60 days of Alzheimer induction and the exercise. Our data demonstrated that spatial memory was indeed impaired in the lesion group compared with the shams. However, exercise notably improved spatial memory in the lesion-exercised rats compared to lesion-rested group. The present results suggest that spatial memory is affected under Alzheimer conditions and that treadmill running improves these effects. Our data suggested that treadmill running contributes to the alleviation of the cognitive decline in AD.
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The present study was undertaken to investigate possible mechanism of pioglitazone-induced beneficial effect in memory deficits associated with experimental dementia. Dementia was induced in Swiss albino mice by administration of streptozotocin (STZ; 3 mg/kg administered intracerebroventricularly on 1st & 3rd day). Morris Water-Maze test was employed to assess learning and memory of the animals. Brain acetylcholinesterase (AChE) activity was measured by Ell Mann's method. Brain thiobarbituric acid reactive species (TBARS) levels and reduced glutathione (GSH) levels were measured by Ohokawa's and Beutler's method respectively to assess total oxidative stress. Blood glucose level was also measured. Streptozotocin (STZ) produced a significant decrease in water-maze performance of mice hence reflecting loss of learning and memory. Pioglitazone (20 mg/kg p.o. daily for 14 days) successfully attenuated STZ-induced memory deficits, without any significant per se effect on blood glucose levels. Higher levels of brain AChE activity, TBARS and lower levels of GSH were observed in STZ treated animals, which were significantly attenuated by pioglitazone. Further, the noted beneficial effect of pioglitazone on STZ-induced dementia was significantly abolished by pre-treatment of nitric oxide (NO) synthase inhibitor L-NAME (3 mg/kg i.p.) manifested in the terms of decrease in water-maze performance and increase in brain AChE activity as well as oxidative stress. It is concluded that anti-dementic effect of pioglitazone may involve central cholinergic, oxidative and NO pathways.
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It has been demonstrated that exercise has neuroprotective effects in the central nervous system (CNS), especially in hippocampus. Previous studies have indicated that diabetes mellitus affects synaptic plasticity in the hippocampus leading to impairments in learning and memory. The aim of this study was to evaluate the effects of treadmill running on synaptic plasticity at dentate gyrus (DG) of streptozotocin-induced diabetic rats. Experimental groups were the control, the diabetes and the diabetes-exercise groups. Long-term potentiation (LTP) in perforant path-DG synapses was assessed (by 400Hz tetanization) in order to investigate the effect of exercise on synaptic plasticity. Field excitatory post-synaptic potential (fEPSP) slope and population spike (PS) amplitude were measured. With respect to the control group, fEPSP were significantly decreased in the diabetes group. However, there were no differences between responses of the diabetes-exercise group and the control. The present results suggest that LTP induction in the dentate gyrus is affected under diabetic conditions and that treadmill running prevents these effects. The data suggest that treadmill running protect against diabetes-induced decrease of learning ability and memory function of the hippocampus.