• Korean Journal of Medicinal Crop Science
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• v.19 no.6
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• pp.456-463
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• 2011

The present study examined the effects of Korean white ginseng (WG, Panax ginseng C. A. Meyer) on the learning and memory function and the neural activity in rats with trimethyltin (TMT)-induced memory deficits. The rats were administered with saline or WG (WG 100 or 300 mg/kg, p.o.) daily for 21 days. The cognitive improving efficacy of WG on the amnesic rats, which was induced by TMT, was investigated by assessing the Morris water maze test and by performing immunohistochemistries on choline acetyltransferase (ChAT), acetylcholinesterase (AchE), cAMP responsive element binding protein (CREB) and brain derived neurotrophic factor (BDNF). The rats treated with TMT injection (control group) showed impaired learning and memory of the tasks, but the rats treated with TMT injection and WG administration produced significant improvement of the escape latency to find the platform in the Morris water maze at the 2nd and 4th days compared to that of the control group. In the retention test, the WG 100 and WG 300 groups showed significantly increased crossing number around the platform compared to that of the control group (p < 0.001). Consistently with the behavioral data, result of immunohistochemistry analysis showed that WG 100 mg/kg significantly alleviated the loss of BDNF-ir neurons in the hippocampus compared to that of the control group (p < 0.01). Also, treatment with WG has a trend to be increased the cholinergic neurons in the hippocampal CA1 and CA3 areas as compared to that of the control group. These results suggest that WG may be useful for improving the cognitive function via regulation of neurotrophic activity.

• Journal of Korean Neurosurgical Society
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• v.44 no.6
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• pp.375-381
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• 2008

Objective : The effects on neural proliferation and differentiation of neural stem cells (NSC) of basic fibroblast growth factor-2 (bFGF). insulin growth factor-I (IGF-I). brain-derived neurotrophic factor (BDNF). and nerve growth factor (NGF) were assessed. Also, following combinations of various factors were investigated : bFGF+IGF-I, bFGF+BDNF, bFGF+NGF, IGF-I+BDNF, IGF-I+NGF, and BDNF+NGF. Methods : Isolated NSC of Fisher 344 rats were cultured with individual growth factors, combinations of factors, and no growth factor (control) for 14 days. A proportion of neurons was analyzed using $\beta$-tubulin III and NeuN as neural markers. Results : Neural differentiations in the presence of individual growth factors for $\beta$-tubulin III-positive cells were : BDNF, 35.3%; IGF-I, 30.9%; bFGF, 18.1%; and NGF, 15.1%, and for NeuN-positive cells was : BDNF, 34.3%; bFGF, 32.2%; IGF-I, 26.6%; and NGF, 24.9%. However, neural differentiations in the absence of growth factor was only 2.6% for $\beta$-tubulin III and 3.1% for NeuN. For $\beta$-tubulin III-positive cells, neural differentiations were evident for the growth factor combinations as follows : bFGF+IGF-I, 73.1 %; bFGF+NGF, 65.4%; bFGF+BDNF, 58.7%; BDNF+IGF-I, 52.2%; NGF+IGF-I, 40.6%; and BDNF+NGF, 40.0%. For NeuN-positive cells : bFGF+IGF-I, 81.9%; bFGF+NGF, 63.5%; bFGF+BDNF, 62.8%; NGF+IGF-I, 62.3%; BDNF+NGF, 56.3%; and BDNF+IGF-I, 46.0%. Significant differences in neural differentiation were evident for single growth factor and combination of growth factors respectively (p<0.05). Conclusion : Combinations of growth factors have an additive effect on neural differentiation. The most prominent neural differentiation results from growth factor combinations involving bFGF and IGF-I. These findings suggest that the combination of a mitogenic action of bFGF and post-mitotic differentiation action of IGF-I synergistically affects neural proliferation and NSC differentiation.

• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.5
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• pp.1080-1086
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• 2009

This study was designed to investigate the effects of Gastrodiae Elata Pharmacopuncure at GB20 on motor control and cognitive dysfunction recovery after mild traumatic brain injury in rats. Rats were divided into three groups; (1) no treatment after traumatic brain injury(experiment I), (2) Treatment with NPA after traumatic brain injury(experiment II), (3) Treatment with GEP after traumatic brain injury(experiment III). In our study, we carried out behavioral test(Rotarod, Morris water maze) and immunohistochemistry study of the change BDNF in the hippocampus(pre, $7^{th}$, $14^{th}$ day). In Rotarod test(motor control function) was significantly increased in the experimental group III as compared with experimental group I, II on $7^{th}$(p<0.01) and $14^{th}$ day(p<0.001). In Morris water maze test(cognitive function) was significantly decreased in the experimental group III as compared with experimental group I, II on $14^{th}$ day(p<0.001). In immunohistochemistric response of BDNF in the hippocampus, the experimental group III was more immune response than the other groups on $14^{th}$ day. These results imply that Gastrodiae Elata Pharmacopuncure at GB20 can play a role in facilitating recovery of motor control and cognitive function after mild traumatic brain injury in rats.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.3
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• pp.556-561
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• 2008

ChongMyeong-Tang (CMT) have been used clinically to treat patient with amnesia and dementia. In addition, CMT have been also used for examinee to improve learning ability in Korea. This study was designed to investigate the effects of Gagam-ChongMeong-Tang (GCMT) on cognitive dysfunction recovery after ischemic brain injury in rats. Rats were divided into three groups; (1) normal, (2) commercial diet after ischemic brain injury (control), (3) CMT diet after ischemic brain injury (experiment). In our study, we carried out Morris water maze test for cognitive motor behavior test and immunohistochemistry study through the change BDNF in the hippocampus($7^{th},\;14^{th}\;day$). In Morris water maze test, cognitive motor function recovery was significantly increased in the experiment group as compared with control group on $7^{th}\;and\;14^{th}\;day$ day (p<0.01). In immunohistochemistric response of BDNF in the hippocampus, more immune reaction was investigated in the experiment group as compared with control group on $7^{th}\;and\;14^{th}\;day$. Especially more immune reaction was experimented $14^{th}$ day. These results imply that GCMT can play a role in facilitating recovery of cognitive function after ischemic brain injury in rats.

• Biomolecules & Therapeutics
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• v.15 no.2
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• pp.83-88
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• 2007

The roots of Liriope platyphylla (Liliaceae) are widely used in traditional Chinese medicine. In the present study, we investigated the effects of ethanol (70%) extract of the roots of Liriope platyphylla (ELP70) on learning and memory using behavioral and immunohistochemical methods in mice. Control animals were treated with vehicle (10% Tween 80). With sub-chronic treatments of ELP70 (p.o.) for 14 days, the latency time was significantly increased compared with that of the vehicle-treated control group (50, 100 and 200 mg/kg; P<0.05). Moreover, immunopositive cells for brain derived neurotrophic factor (BDNF) were significantly increased in the hippocapmpal dentate gyrus and CA1 regions after ELP70 treatments for 14 days (50, 100 and 200 mg/kg; P < 0.05). In addition, those cells for nerve growth factor (NGF) were also increased in the hippocapmpal dentate gyrus region (50, 100 and 200 mg/kg; P<0.05). These results suggest that the sub-chronic administration of ELP70 improves learning and memory, and that their beneficial effects are mediated, in part, by the enhancement of BDNF or NGF expression.

• Journal of Physiology & Pathology in Korean Medicine
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• v.25 no.1
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• pp.37-47
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• 2011

This study was aimed to investigate the memory enhancing effect of Jeongjihwan against scopolamine-induced amnesia in C57BL/6 mice. To determine the effect of Jeongjihwan on the memory and cognitive function, we have injected scopolamine (1 mg/kg, i.p.) into C57BL/6 mice 30 min before beginning of behavior tests. We have conducted Y-maze, Morris water-maze, passive avoidance and fear conditioning tests to compare learning and memory functions. Scopolamine-induced behavior changes of memory impairment were significantly restored by oral administration of Jeongjihwan (100 or 200 mg/kg/day). To elucidate the molecular mechanism underlying the memory enhancing effect of Jeongjihwan, we have examined the antioxidant defense system and neurotrophic factors. Jeongjihwan treatment attenuated intracellular accumulation of reactive oxygen species and up-regulated mRNA and protein expression of antioxidant enzymes as assessed by RT-PCR and western blot analysis, respectively. Jeongjihwan also increased protein levels of brain-derived neurotrophic factor (BDNF) compared with those in the scopolamine-treated group. Furthermore, as an upstream regulator, the activation of cAMP response element-binding protein (CREB) via phosphorylation was assessed by Western blot analysis. Jeongjihwan elevated the phosphorylation of CREB (p-CREB), which seemed to be mediated partly by extracellular signal-regulated kinase1/2 (ERK1/2) and protein kinase B/Akt. These findings suggest that Jeongjihwan may have preventive and therapeutic potential in the management of amnesia.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.4
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• pp.357-366
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• 2016

Pro-inflammatory cytokine and brain-derived neurotrophic factor (BDNF) are modulated in post-traumatic stress disorder (PTSD). This study investigated the effects of ibuprofen (IBU) on enhanced anxiety in a rat model of PTSD induced by a single prolonged stress (SPS) procedure. The effects of IBU on inflammation and BDNF modulation in the hippocampus and the mechanisms underlying for anxiolytic action of IBU were also investigated. Male Sprague-Dawley rats were given IBU (20 or 40 mg/kg, i.p., once daily) for 14 days. Daily IBU (40 mg/kg) administration significantly increased the number and duration of open arm visits in the elevated plus maze (EPM) test, reduced the anxiety index in the EPM test, and increased the time spent in the center of an open field after SPS. IBU administration significantly decreased the expression of pro-inflammatory mediators, such as tumor necrosis $factor-{\alpha}$, $interleukin-1{\beta}$, and BDNF, in the hippocampus, as assessed by reverse transcription-polymerase chain reaction analysis and immunohistochemistry. These findings suggest that IBU exerts a therapeutic effect on PTSD that might be at least partially mediated by alleviation of anxiety symptoms due to its anti-inflammatory activity and BDNF expression in the rat brain.

• Korean Journal of Biological Psychiatry
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• v.16 no.3
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• pp.170-180
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• 2009

Objectives : To assess clinical improvement and change in plasma brain-derived neurotrophic factor(BDNF) level after repetitive transcranial magnetic stimulation(rTMS) in patients with treatment-resistant schizophrenia. Methods : Seven patients with DSM-IV schizophrenia, who were proven to be treatment-resistant, were treated with 15 sessions of rTMS for three weeks as an adjuvant therapy to antipsychotic treatment. Clinical improvement and change in plasma BDNF level were measured after the treatment period. The symptom severity was assessed with the Positive and Negative Syndrome Scale(PANSS) and the Korean Version of Calgary Depression Scale for Schizophrenia(K-CDSS) at baseline and 7 days after the treatment. Plasma BDNF level was measured by enzyme-linked immunosorbent assay(ELISA) at baseline and 7 days after the treatment. Results : After the rTMS treatment, there was no significant improvement in PANSS total score(Z=-1.693, p=0.090) and no significant change in plasma BDNF was found(Z=-1.183, p=0.237). Negative correlations were found between percentage change in PANSS positive subscale score and duration of illness(rho=-0.991, N=7, p<0.0005, two-tailed), and PANSS negative subscale score at baseline and percentage change in plasma BDNF level(rho=-0.821, N=7, p=0.023, two-tailed). Conclusion : This preliminary study suggests that rTMS didn't make a significant change in clinical symptoms nor in plasma BDNF level in treatment-resistant schizophrenia. Percentage change in plasma BDNF, however, might be correlated with treatment resistance in schizophrenic patients. This is a pilot study with a small sample size, therefore, a further study with a larger sample size is needed.

• Journal of Life Science
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• v.19 no.3
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• pp.403-410
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• 2009

This study investigated the effects of treadmill exercise on memory ability, cell proliferation, BDNF, and TrkB in the hippocampus and forebrain cholinergic cells in adolescent rats. Male Sprague-Dawley rats (4 weeks old) were randomly assigned to the following two groups: the sedentary group (n=10) and the exercise group (n=10). Rats in the exercise group were forced to run on a treadmill for 30 min, five times per week for 4 weeks. The latency of the step-through avoidance task was used in order to evaluate memory ability. Hippocampal brain-derived neurotrophic factor (BDNF) and tropomyosin-related kinase B (TrkB) expression were assessed by Western blotting. Hippocampal cell proliferation and forebrain cholinergic cells were assessed by immunohistochemistry. The present study showed that treadmill running during the adolescent period significantly improved memory capability, increased hippocampal cell proliferation, up-regulated hippocampal BDNF and TrkB expression, and enhanced the number of forebrain cholinergic cells. These results suggest that regular exercise during the adolescent period may enhance memory function.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.6
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• pp.579-589
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• 2017

Anesthetics are used extensively in surgeries and related procedures to prevent pain. However, there is some concern regarding neuronal degeneration and cognitive deficits arising from regular anesthetic exposure. Recent studies have indicated that brain-derived neurotrophic factor (BDNF) and cyclic AMP response element-binding protein (CREB) are involved in learning and memory processes. Genistein, a plant-derived isoflavone, has been shown to exhibit neuroprotective effects. The present study was performed to examine the protective effect of genistein against isoflurane-induced neurotoxicity in rats. Neonatal rats were exposed to isoflurane (0.75%, 6 hours) on postnatal day 7 (P7). Separate groups of rat pups were orally administered genistein at doses of 20, 40, or 80 mg/kg body weight from P3 to P15 and then exposed to isoflurane anesthesia on P7. Neuronal apoptosis was detected by TUNEL assay and FluoroJade B staining following isoflurane exposure. Genistein significantly reduced apoptosis in the hippocampus, reduced the expression of proapoptotic factors (Bad, Bax, and cleaved caspase-3), and increased the expression of Bcl-2 and Bcl-xL. RT-PCR analysis revealed enhanced BDNF and TrkB mRNA levels. Genistein effectively upregulated cAMP levels and phosphorylation of CREB and TrkB, leading to activation of cAMP/CREB-BDNF-TrkB signaling. PI3K/Akt signaling was also significantly activated. Genistein administration improved general behavior and enhanced learning and memory in the rats. These observations suggest that genistein exerts neuroprotective effects by suppressing isoflurane-induced neuronal apoptosis and by activating cAMP/CREB-BDNF-TrkB-PI3/Akt signaling.