• Journal of mucopolysaccharidosis and rare diseases
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• v.4 no.1
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• pp.26-36
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• 2018

Mucopolysaccharidosis IIIA is a heritable neurodegenerative disorder resulting from the dysfunction of the lysosomal hydrolase sulphamidase. This leads to the primary accumulation of the complex carbohydrate heparan sulphate in a wide range of tissues and CNS degeneration. Characterization of animal model is the beginning point of the therapeutic clinical trial. Mouse model has a limitation in that it is not a human and does not have all of the disease phenotypes. Therefore, delineate of the phenotypic characteristics of MPS IIIA mouse model prerequisite for the enzyme replace treatment for the diseases. We designed 6-month duration of phenotypic characterization of MPS IIIA mouse biochemically, behaviorally and histologically. We compared height and weight of MPS IIIA mouse with wild type from 4 weeks to 6 months in both male and female. At 6 months, we measured GAG storage in urine kidney, heart, liver, lung and spleen. The brain GAG storage is presented with Alcian blue staining, immunohistochemistry, and electron-microscopy. The neurologic phenotype is evaluated by brain MRI and behavioral study including open field test, fear conditioning, T-maze test and Y-maze test. Especially behavioral tests were done serially at 4month and 6month. This study will show the result of the MPS IIIA mouse model phenotypic characterization. The MPS IIIA mouse provides an excellent model for evaluating pathogenic mechanisms of disease and for testing treatment strategies, including enzyme or cell replacement and gene therapy.

• The Korean Journal of Physiology and Pharmacology
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• v.13 no.2
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• pp.85-89
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• 2009

Puerariae flos (PF) is a traditional oriental medicinal plant and has clinically been prescribed for a long time. The purpose of the present study was to examine the effect of PF on repeated stress-induced alterations of learning and memory on a Morris water maze (MWM) test in ovariectomized (OVX) female rats. The changes in the reactivity of the cholinergic system were assessed by measuring the immunoreactive neurons of choline acetyltransferase (ChAT) in the hippocampus after behavioral testing. The female rats were randomly divided into four groups: the nonoperated and nonstressed group (normal), the sham-operated and stressed group (control), the ovariectomized and stressed group (OS), and the ovariectomized, stressed and PF treated group (OSF). Rats were exposed to immobilization stress (IMO) for 14 d (2 h/d), and PF (400 mg/kg, p.o.) was administered 30 min before IMO stress. Results showed that treatments with PF caused significant reversals of the stress-induced deficits in learning and memory on a spatial memory task, and also increased the ChA T immunoreactivities. In conclusion, administration of PF improved spatial learning and memory in OVX rats, and PF may be useful for the treatment of postmenopausal-related dementia.

• Journal of Applied Biological Chemistry
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• v.64 no.3
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• pp.299-307
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• 2021

Accumulation of amyloid beta (Aβ) and oxidative stress are the most common reason of Alzheimer's disease (AD). In the present study, we investigated the cognitive improvement effects of butanol (BuOH) fraction from Momordica charantia in Aβ_25-35-induced AD mouse model. To develop an AD mouse model, mice were received injection of Aβ_25-35, and then orally administered BuOH fraction from M. charantia at doses of 100 and 200 mg/kg/day during 14 days. In the T-maze and novel object recognition test, administration of BuOH fraction from M. charantia L. at doses of 100 and 200 mg/kg/day improved spatial ability and novel object recognition by increased explorations of novel route and new object. In addition, BuOH fraction of M. charantia-administered groups improved learning and memory abilities by decreased time to reach hidden platform in Morris water maze test. Oral administration of BuOH fraction from M. charantia significantly inhibited lipid peroxidation and nitric oxide levels in the brain, liver, and kidney compared with Aβ_25-35-induced control group. These results indicated that BuOH fraction of M. charantia improved Aβ_25-35-induced cognitive impairment by attenuating oxidative stress. Therefore, M. charantia could be useful for protection from Aβ_25-35-induced cognitive impairment.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.6
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• pp.1236-1242
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• 2002

In order to make an efficient prescription and cope with dementia, learning and memory functions of Sprague-Dawley model rats were tested with Morris water maze. And to evaluate the effect of the sample drug(CHM) on choline acetyltranferase and acetylcholine esterase, immunoreactive measurement and enzymatic activity measuring were carried out. Rats were injected with ibotenic acid through hippocampus CA1 and CA3 area. The results are as following. CHM improves the learning ability in the acquisition test and memory function in the retention test significantly. And CHM increases the level of AChE which is resolving acetylcholine. Though it doesn't increase the level of ChAT significantly which is synthesizing acetylcholine, but it shows the tendency of increase. So these results show that CHM improve the cholinergic catabolism and anabolism, and the increment of metabolic activity of cholinergic system. Thus it can be concluded that CHM will be helpful to cholinergic brain disease induced by primary or senile reduction of acetylcholine secretive activity.

• Biomolecules & Therapeutics
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• v.14 no.2
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• pp.83-89
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• 2006

The main aim of this study was to characterize the pharmacological profile of flavonoids utilizing behavioral tests and to investigate how the psychopharmacological activities of wogonin, baicalein and oroxylin A are different. Wogonin, baicalein and oroxylin A were intraperitoneally injected as dosages of 2.5, 5, 10 and 20 mg/kg. In the locomotor activity, Rota-rod test, and elevated plus-maze tests, the behavioral parameters were analyzed by automatic systems. Thiopental induced sleeping time was measured. Water extract of S. baicalensis didn't exhibit sedative effect. Wogonin and bacalein exhibited anxiolytic activity although it was less potent than buspirone. Wogonin and baicalein decreased locomotor activity at a dose of 10 mg/kg. Wogonin also shortened significantly running time on the rota-rod at doses of 5 and 10 mg/kg. Wogonin and baicalein enhanced sleeping at doses of 5 and 10 mg/kg. These results indicate that wogonin produce anxiolysis with sedation and so did bacalein with mild sedation. On the contrary, oroxylin A enhanced running activity on the rotarod and did't depress locomotor activity. Oroxylin A significantly hindered sleeping rather than helped it at doses of 5 and 10 mg/kg. Oroxylin A didn't produce anxiolysis and instead, produce awakening effect. This study demonstrates that wogonin and bacalein exhibited anxiolytic activity with mild sedation, but oroxylin A didn't produce anxiolysis and instead, produce awakening effect. This result indicates that anxiolytic effect without sedation induced by Scutellaria baicalensis is produced by combination of flavonoids.

• Toxicological Research
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• v.32 no.4
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• pp.275-280
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• 2016

Prenatal nicotine exposure over an entire pregnancy has been associated with an increased prevalence of hyperactivity, anxiety-like behavior and depression-like behavior in mature rats. However, the effects of maternal nicotine exposure in late gestation and lactation on the psychology and behavior of adolescent rat offspring are unclear. Thus, we investigated the effect of nicotine exposure during late gestation and lactation on anxiety-like and impulsive decision-making behavior in adolescent offspring of rat. Female rats were orally exposed to nicotine which is within range of plasma level of human chronic smokers during the period of third last period of gestation and lactation. When the offspring were weaned, we observed alterations in the anxiety-like behavior and decision-making ability of adolescent rat offspring using light/dark box test and T-maze delay-based cost-benefit decision-making task. The maternal consumption of nicotine reduced both the time spent in the light compartment and the number of transitions compared to nicotine-free rats. Moreover, such nicotine exposed adolescent offspring rats showed impulsive decision making which chose the instant reward in a decision-making situation. We found that nicotine exposure during late gestation and lactation induces an increase in anxiety-like and impulsive decision-making behavior at this developmental stage. These findings suggest that maternal nicotine-exposed offspring are at an increased risk of developing anxious and impulsive behavior.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.1
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• pp.50-56
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• 2003

This research was done to make the effective prescription and cope with various senile dementia. So Sprague-Dawley rats were injected with ibotenate to make a damage on learning and memory functions. At first acquisition test and retention rest were done in the Morris water maze. And to evaluate the effects of the sample drug(TBM) on choline acetyltranferase and acetylcholine esterase, immunoreactive measurement and enzymatic activity measuring were carried out. The ibotenic acid were injected to hippocampus CA1 and CA3 area. The results were as following. TBM improved the learning ability in the acquisition test and memory function in the retention test significantly. And TBM increased the level of ChAT which is synthesizing acetylcholine in CA3 area, and at the same time it increased the level of AChE which is resolving acetylcholine. These results show that T8M improved the cholinergic catabolism and anabolism, and the increment of metabolic activity of cholinergic system. In other words, it contributes to the recovery of damaged learning and memory function by ibotenic acid. So it can be concluded that TBM will be helpful to cholinergic brain damage induced by primary or senile reduction of acetylcholine secretive activity.

• The Journal of Korean Medicine
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• v.26 no.2 s.62
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• pp.32-51
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• 2005

Objectives: To study the effect of Artemisiae Capillaris Herba extracts, that have been used as oriental medicine to treat liver disease, on the perinatal and lactational n;)productive toxicity of SD rats when administered by oral lavage. Methods: Female SD rats were dosed from 6 days of gestation to 3 weeks postpartum. This was conducted in accordance with the recommendations of the KFDA Guidelines for Detection of Toxicity to Reproduction for Medicinal Products. Results: No Artemisiae Capillaris Herba extracts treatment-related changes in clinical signs, mortalities, implantation number, dead fetus number, loss rate of fetus, number of live young, survival rate of fetus, sex ratio of live young, external anomalies, pregnancy periods, viability index, lactational index, survival rate of litters at 4 days after birth or delivery index were demonstrated in any dosed levels in this study. However, the body weight and gains, food consumption and absolute organ weights of brain, adrenal glands, liver, spleen, kidney, ovaries and heart were significantly increased in 2000 or 1000mg/kg-dosing groups and the relative organ Weights of adrenal glands were significantly increased in 2,000mg/kg-dosing groups. Therefore, it was concluded that this increase was natural according to growth. Also, no changes of gross findings, clinical signs, mortalities, body weight and gains, physical development results, necropsy findings, organ weight, faculty test, open filed test and water-filled simple T-maze test, copulation, fertility, pregnancy indices, body weight and gains during gestation periods, necropsy findings, corpora lutea number, implantation number, implantation rate, dead fetus number, post-implantation loss rate, live young, post-implantation survival rate, sex ratio of live young, external anomalies and individual body weights of live young were demonstrated in any dosed levels in this study. Conclusions: It is considered that the NOAEL (No-Observed-Adverse-Effect Level) for perinatal and lactational reproductive toxicity of Artemisiae Capillaris Herba extracts was up to 2000mg/kg/day because no changes of other perinatal and lactational reproductive indices were demonstrated.

• Biomolecules & Therapeutics
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• v.13 no.3
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• pp.165-173
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• 2005

The main aim of this study was to investigate stress related activities of ginsenosides and their action mechanism. Control group and ginsenoside supplemented groups were exposed to stress while no-stress group was not done. Animals of each group (n=$8\~10$) were orally administerd 100 mg red ginseng extract (R-G), or 10 mg ginsenosides/kg body weight once a day. Animals were given materials for 5 days without stress, and then were given supplements for 5 days with restraint and electroshock stress. Mice were given materials for 5 days for experiments on anti-fatigue effect. After loading final stress, stress-related behavioral changes of experimental animals were examined and plasma corticosterone levels were measured. R-G and ginsenoside $Rb_{1}$ supplementation partially blocked the stress effects on locomotion and elevated plus-maze test in rats and mice. They also partially blocked stress induced behavioral changes such as freezing, smelling, face-washing, rearing behavior in rats. R-G and $Rb_{1}$ decrease adrenal gland size and plasma corticosterone level, which were increased by stress in rats. R-G increased enduring time on the Rota rod, cold water and horizontal wire, but $Rb_{1}$ didn't. Effects of $Rb_{1}$ on plusmaze test were inhibited by administration of flumazenil. These results suggest that $Rb_{1}$ is the main antistress principle in ginseng and it's effect is modulated by GABAnergic nervous system.

• Journal of Oriental Neuropsychiatry
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• v.24 no.4
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• pp.419-434
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• 2013

Objectives: The object of this study is to observe the cognition and motor function recovery effects of Joojakwhan (JJW), a traditional Korean poly-herbal formula for treating various neuropsychiatric diseases such as dementia, for the mildly stroke rats, with 60 minutes of reperfusion transient middle cerebral artery occlusion (tMCAO). Methods: In the present study, 125, 250 and 500 mg/kg of JJW were orally administered, once per day for 10 continuous days 2 hours after the tMCAO. The body weight changes, infarct sizes under 2% 2, 3, 5-triphenyl tetrazolium chloride (TTC) stain, sensorimotor functions and cognitive motor behavior tests were serially monitored with cerebral caspase-3 and cleaved poly (ADP-ribose) polymerase (PARP)-immunoreactivities and histopathological changes. The effects of tMCAO on sensorimotor functions were evaluated by using of limb placing and body-swing tests, and the cognitive motor behaviors were also observed with water maze tests. Results: From the results of tMCAO, with marked decreases of body weights, disorders of sensorimotor functions increases the limb placing test scores, and decrease the numbers and percentages of body swings to the ipsilateral sides. The cognitive motor behaviors increases the distances and time to reach the escape platform which included the inhibitions of the decreases with repeated trials that were observed with focal cerebral cortex infarct volumes. In addition, the marked increases of the atrophy, numbers of degeneration, caspase-3- and PARP-immunoreactive cells around peri-infarct ipsilateral cerebral cortex were also observed in tMCAO controls when compared with the sham control rats, respectively. Conclusions: The results obtained from this study suggest that oral administrations of JJW indicate obvious cognitions and motor function recoveries of the rats with tMCAO, mild strokes, which are mediated by neuro-protective effects through known antioxidant effects of components.