• 생물정신의학
• /
• 제8권1호
• /
• pp.3-19
• /
• 2001

Recent basic and clinical studies demonstrate a major role for neural plasticity in the etiology and treatment of depression and stress-related illness. The neural plasticity is reflected both in the birth of new cell in the adult brain(neurogenesis) and the death of genetically healthy cells(apoptosis) in the response to the individual's interaction with the environment. The neural plasticity includes adaptations of intracellular signal transduction pathway and gene expression, as well as alterations in neuronal morphology and cell survival. At the cellular level, repeated stress causes shortening and debranching of dendrite in the CA3 region of hippocampus and suppress neurogenesis of dentate gyrus granule neurons. At the molecular level, both form of structural remodeling appear to be mediated by glucocorticoid hormone working in concert with glutamate and N-methyl-D-aspartate(NMDA) receptor, along with transmitters such as serotonin and GABA-benzodiazepine system. In addition, the decreased expression and reduced level of brain-derived neurotrophic factor(BDNF) could contribute the atrophy and decreased function of stress-vulnerable hippocampal neurons. It is also suggested that atrophy and death of neurons in the hippocampus, as well as prefrontal cortex and possibly other regions, could contribute to the pathophysiology of depression. Antidepressant treatment could oppose these adverse cellular effects, which may be regarded as a loss of neural plasticity, by blocking or reversing the atrophy of hippocampal neurons and by increasing cell survival and function via up-regulation of cyclic adenosine monophosphate response element-binding proteins(CREB) and BDNF. In this article, the molecular and cellular mechanisms that underlie stress, depression, and action of antidepressant are precisely discussed.

• Journal of Korean Neurosurgical Society
• /
• 제49권1호
• /
• pp.1-7
• /
• 2011

Objective: Glutamate is a key excitatory neurotransmitter in the brain, and its excessive release plays a key role in the development of neuronal injury. In order to define the effect of nimodipine on glutamate release, we monitored extracellular glutamate release in real-time in a global ischemia rat model with eleven vessel occlusion. Methods: Twelve rats were randomly divided into two groups: the ischemia group and the nimodipine treatment group. The changes of extracellular glutamate level were measured using microdialysis amperometric biosensor, in coincident with cerebral blood flow (CBF) and electroencephalogram. Nimodipine (0.025 ${\mu}g$/100 gm/min) was infused into lateral to the CBF probe, during the ischemic period. Also, we performed Nissl staining method to assess the neuroprotective effect of nimodipine. Results: During the ischemic period, the mean maximum change in glutamate concentration was $133.22{\pm}2.57\;{\mu}M$ in the ischemia group and $75.42{\pm}4.22\;{\mu}M$ (p<0.001) in the group treated with nimodipine. The total amount of glutamate released was significantly different (P<0.001) between groups during the ischemic period. The %cell viability in hippocampus was $47.50{\pm}5.64$ (p<0.005) in ischemia group, compared with sham group. But, the %cell viability in nimodipine treatment group was $95.46{\pm}6.60$ in hippocampus (p<0.005). Conclusion: From the real-time monitoring and Nissl staining results, we suggest that the nimodipine treatment is responsible for the protection of the neuronal cell death through the suppression of extracellular glutamate release in the 11-VO global ischemia model of rat.

• 동의신경정신과학회지
• /
• 제21권1호
• /
• pp.71-88
• /
• 2010

Objectives: This research investigates the effect of the DHJHT extract on Alzheimer's disease. Specifically, the effects of the DHJHT extract on (1) the behavior (2) the infarction area of the hippocampus, and brain tissue injury in AD mice induced with ${\beta}A$ were investigated. Methods: The effects of the DHJHT extract on the proinflammation cytokines mRNA expression and production of BACE, APP and ${\beta}A$ in in BV2 microglial cell line treated by lipopolysacchaide(LPS) plus ${\beta}A$ were investigated. The effects of the DHJHT extract on the behavior of the memory deficit mice induced by scopolamine were investigated. Results: 1. The DHJHT extract suppressed the expression of IL-$1{\beta}$, IL-6, TNF-$\alpha$, COX-2, and NOS-II, BACE and APP mRNA in BV2 microglial cell line treated by LPS plus ${\beta}A$. 2. The DHJHT extract suppressed the expression of ${\beta}A$ production in BV2 microglial cell line treated with LPS plus ${\beta}A$. 3. The DHJHT extract showed significantly inhibitory effect on the scopolamine-induced impairment of memory in the experiment of Morris water maze. 4. The DHJHT group suppressed the expression of IL-$1{\beta}$, TNF-$\alpha$, MDA, and CD68+/CD11b+ in the brain tissue of the mice with AD induced by ${\beta}A$. 5. The DHJHT group reduced the infarction area of hippocampus, and controlled the injury of the brain tissue in the mice with AD induced by ${\beta}A$. 6. The DHJHT group reduced tau protein, and GFAP in the brain tissue of the mice with AD induced by ${\beta}A$. Conclusions: These results suggest that the DHJHT group may be effective for the treatment of AD. Thus, DHJHT could be considered among the future therapeutic drugs indicated for the treatment of AD.

• 동의신경정신과학회지
• /
• 제19권2호
• /
• pp.95-110
• /
• 2008

Objective : This experiment was designed to investigate the effects of the PMCMT hot water extract & ultra-fine powder on Alzheimer's Disease Model Induced by ${\beta}A$. Method : The effects of the PMCMT hot water extract on expression of proinf1ammatory cytokine mRNA in BV2 microglial cell cell line treated by lipopolysacchaide(LPS). The effects of the PMCMT hot water extract & ultra-fine powder on (1) the behavior (2) AChE in serum (3) the infarction area of the hippocampus, and brain tissue injury in Alzheimer's diseased mice induced with ${\beta}A$ were investigated. Result : 1. The PMCMT hot water extract suppressed the expression of proinflammatory cytokine mRNA in BV2 microglial cell line treated with LPS. 2. The PMCMT hot water extract & ultra-fine powder a significant inhibitory effect on the memory deficit was shown for the mice with Alzheimer's disease induced by ${\beta}A$ in the Morris water maze experiment, which measured stop-through latency and distance movement-through latency 3. The PMCMT hot water extract & ultra-fine powder suppressed the over-expression of AChE activity in the serum of the mice with Alzheimer's disease induced by ${\beta}A$. 5. The PMCMT ultra-fine powder reduced infarction area of hippocampus significantly, and the PMCMT hot water extract & ultra-fine powder controlled the injury of brain tissue in the mice with Alzheimer's disease induced by ${\beta}A$. Conclusions : These results suggest that the PMCMT hot water extract & ultra-fine powder may be effective for the prevention and treatment of Alzheimer's disease. Investigation into the clinical use of the PMCMT hot water extract & ultra-fine powder for Alzheimer's disease is suggested for future research.

• 한국한의학연구원논문집
• /
• 제8권1호
• /
• pp.109-126
• /
• 2002

The herbal extract (YMT_02) is a modified herbal extracts from Yukmijihwangtang (YMJ) to promote memory-enhancing. The YMJ extracts has been widely used as an anti-aging herbal medicine for hundred years in Asian countries. The purpose of this study is to; 1) quantitatively evaluate the memory-enhancing effect of YMT_02 by hehavior task, 2) identify candidate genes responsible for enhancing memory by cDNA microarray and 3) assess the anti-oxidant effect of YMT_02 on PC12 cell. Memory retention abilities are addressed by passive avoidance task with Sprague-Dawley (SD) male rat. Before the training session, the rats are subdivided into four groups and administrated with YMT_02, Ginkgo biloba, Soya lecithin and normal saline for 10 days. The retention test was performed. 24 hours after the training session. The retention time of the YMT_02 group was significantly (p<0.05) delayed $({\sim}100%)$, whereas Ginkgo biloba and Soya lecithin treatment delayed 20% and 10% respectively. The hippocampi of YMT_02 and control group were dissected and mRNA was further purified. After synthesizing cDNA using oligo-dT primer, the cDNA were applied and mRNA was further purified. After synthesizing cDNA using oligo-dT primer, the cDNA were applied to Incyte rat GEMTM 2 cDNA microarray. The microarray results show that prealbumin(transthyretin), phosphotidy lethanolamine N-methyltransferase, and PEP-19 are expressed abundantly in the YMT_02 treated group. Especially, PEP-19 is a neuron-specific protein, which inhibits apoptotic processes in neuronal cell. On the other hand, transcripts of RAB15, glutamate receptor subunit 2 and CDK 108 are abundant in control group. Besides, neuronal genes involved in neuronal death or neurodegeneration such as neuronal-pentraxin and spectrin are abundantly expressed in control group. Additionally, the YMT_02 shows an anti oxidative effect in the PC12 cell. The list of differentially expressed genes may implicate further insight on the action and mechanism behind the memory-enhancing effect of herbal extracts YMT_02, for example, anti-apoptotic, anti-oxidative, and neuroprotective effects.

• The Korean Journal of Physiology and Pharmacology
• /
• 제22권3호
• /
• pp.301-309
• /
• 2018

Statins mediate vascular protection and reduce the prevalence of cardiovascular diseases. Recent work indicates that statins have anticonvulsive effects in the brain; however, little is known about the precise mechanism for its protective effect in kainic acid (KA)-induced seizures. Here, we investigated the protective effects of atorvastatin pretreatment on KA-induced neuroinflammation and hippocampal cell death. Mice were treated via intragastric administration of atorvastatin for 7 days, injected with KA, and then sacrificed after 24 h. We observed that atorvastatin pretreatment reduced KA-induced seizure activity, hippocampal cell death, and neuroinflammation. Atorvastatin pretreatment also inhibited KA-induced lipocalin-2 expression in the hippocampus and attenuated KA-induced hippocampal cyclooxygenase-2 expression and glial activation. Moreover, AKT phosphorylation in KA-treated hippocampus was inhibited by atorvastatin pretreatment. These findings suggest that atorvastatin pretreatment may protect hippocampal neurons during seizures by controlling lipocalin-2-associated neuroinflammation.

• 생물정신의학
• /
• 제5권1호
• /
• pp.83-94
• /
• 1998

Objectives : Phencyclidine(PCP) or PCP-like substances such as ketamine have been known to rekindle the cognitive dysfunction in schizophrenia. The aims of this study were to identify whether PCP-like substances can produce cognitive deficit in schizophrenia, to discuss relation with aging process, and finally to speculate underlying neurochemical mecha-nisms by various drug responses. Methods : In experiment I, radial maze tests were done in 24 Sprague-Dawley rats for 3 days to get baseline data. Being divided into 4 groups(6 rats respectively) of normal aged, normal adult controls, atropine-treated and ketamine-treated, the radial maze tests were repeated on every week for 6 weeks, and then the rats were sacrificed by intracardiac perfusion with phosphate-buffered 10% formaldehyde solution for histology. The brain specimen was stained with hematoxylin-eosin to count cells in the prefrontal cortex and hippocampus. In experiment II, radial maze tests were done for 48 rats before any drug treatment and only after ketamine administration. Thereafter, haloperidol, bromocriptine, clonidine, nimodipine, tacrine, valproic acid, naloxone and fluoxetine were intramuscularly injected on every other day in addition to ketamine. Radial maze tests were repeated on every week for 6 weeks, and then rats were prepared by the same procedure for histology. Results : 1) Reaction times of radial maze tests of atropine-treated rats were significantly prolonged than those of normal aged(p<0.05) or normal adult controls(p<0.05). Cell numbers of prefrontal cortex & hippocampus in ketamine-treated rats were significantly reduced than those in normal aged (p<0.05) or normal adult controls(p<0.005). 2) Reduced cell numbers by ketamine became significantly raised by tacrine administration in prefrontal cortex & hippocampus(p<0.05), while there were no significant changes on radial maze tests. Cell numbers also tended to be raised by nimodipine, fluoxetine and haloperidol administration. Conclusions : In conclusion, the visuospatial memory disorders in ketamine-induced psychotic rats might be partly asso-ciated with aging process. Furthermore, the responses to the various drugs suggested cholinergic system might have an important role in the neurochemical mechanism of the cognitive dysfunction in ketamine-induced psychosis. Otherwise, calcium metabolism as well as serotonergic and dopaminergic systems seemed to be possibly related.

• 동의신경정신과학회지
• /
• 제18권2호
• /
• pp.101-132
• /
• 2007

Objective : This research investigates the effect of the NogYongDaeBoTang,(NYDBT) on Alzheimer's disease. Method : The effects of the NYDBT extract on (1) $IL-1{\beta}$, IL-6, and $TNF-{\alpha}$ mRNA of PC-12 cells treated with LPS; (2) acetylcholinesterase(AChE), amyloid precursor proteins(APP), and glial fibrillary acidic protein(GFAP) mRNA the AChE activity and the APP production of PC-12 cell treated with CT-105; (3) the behavior; (4) expression of $IL-1{\beta}$, $TNF-{\alpha}$, MDA, $IL-1{\beta}$ mRNA, and $TNF-{\alpha}$ mRNA; (5) the infarction area of the hippocampus, and brain tissue injury in Alzheimer‘s diseased mice induced with ${\beta}A$ were investigated. Results : 1. The NYDBT extract suppressed the expression of $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$ mRNA in BV2 microglia cell line treated with LPS. 2. The NYDBT extract suppressed the expression of $IL-1{\beta}$, IL-6, and $TNF-{\alpha}$ protein production in BV2 microglia cell line treated with LPS. 3. For the NYDBT extract group a significant inhibitory effect on the memory deficit was shown for the mice with Alzheimer's disease induced by $A{\beta}$ in the Morris water maze experiment, which measured stop-through latency, and distance movement-through latency. 4. The NYDBT extract suppressed the over-expression of $IL-1{\beta}$ protein, $TNF-{\alpha}$ protein, MDA, and CD68/CD11b, in the mice with Alzheimer's disease induced by $A{\beta}$. 5. The NYDBT extract reduced the infarction area of hippocampus, and controlled the injury of brain tissue in the mice with Alzheimer's disease induced by $A{\beta}$. 6. The NYDBT extract reduced the Tau protein, GFAP protein, and presenilin1/2 protein (immunohistochemistry) of hippocampus in the mice with Alzheimer's disease induced by $A{\beta}$. Conclusions : These results suggest that the NYDBT extract may be effective for the prevention and treatment of Alzheimer's disease.

• Korean Journal of Acupuncture
• /
• 제21권1호
• /
• pp.15-27
• /
• 2004

Objectives : Acupuncture has been used to prevent and treat the cerebrovascular accident, such as a stroke, and many studies of acupuncture and moxibustion concerning to the stroke have been undertaken in the human and various animals. Also, herbal acupuncture, namely aqua acupuncture has been applied and developed to various diseases including the cerebrovascular accident. FOLIUM ARTEMISIAE ARGYI is the dry leaf of Artemisia argyi Levl. et Vant. collected in summer before the plant blooms and used to moxibustion and has been recommended for use as an analgesic and hemostatic. In this study, effects of FOLIUM ARTEMISIAE ARGYI (艾葉)' herbal acupuncture on the $LR_3$, namely Taechung on neuroprotection after the transient forebrain ischemia were investigated in Sprague-Dawely rats. Methods : Expressions of neuronal nitric oxide synthase (nNOS) protein in the hippocampus and cortex were observed at 2 hrs after transient forebrain ischemia by immunohistochemistry. Results : Expression of nNOS protein was increased in the hippocampus and cortex at 2 hrs after transient forebrain ischemia. However, pretreatment with FOLIUM ARTEMISIAE ARGYI' herbal acupuncture on $LR_3$ significantly decreased expression of nNOS protein protein compared to ischemia group. These features were observed in the motor cortex and the hippocampus. Conclusions : These results suggest that pretreatment with FOLIUM ARTEMISIAE ARGYI' herbal acupuncture on $LR_3$ inhibits the expression of nNOS protein induced by transient forebrain ischemia and may modulate excitatory toxicity of neuron related to neuronal cell death.

• 대한한의학회지
• /
• 제26권3호
• /
• pp.146-161
• /
• 2005

Objectives : This study investigated neuroprotective effects of Polygoni Multiflori Radix on cerebral ischemia of hyperlipidemic rats. Methods : Effects of Polygoni Multiflori Radix were evaluated with changes of infarct size after He focal cerebral ischemia induced by the middle cerebral artery occlusion, changes of pyramidal neurons and expressions of Bax and Bcl-2 apoptosis regulating factors after global cerebral ischemia, and changes of serum lipid revels after cerebral ischemia. Results & Conclusions : Results obtained were as follows; 1. Polygoni Multiflori Radix did net reduce the focal cerebral infarct size induced by the middle cerebral artery occlusion under both hyperlipidemic and normal-lipid conditions. 2. Polygoni Multiflori Radix significantly reduced the increase of neuronal cell death in CAl region of hippocampus induced by the global cerebral ischemia under both hyperlipidemic and normal-lipid conditions. 3. Polygoni Multiflori Radix significantly reduced the increase of Bax expression in the CAl region of the hippocampus induced by global cerebral ischemia under both hyperlipidemic and normal-lipid conditions. 4. Polygoni Multiflori Radix significantly increased Bc1-2 expression in the CA1 region of the hippocampus after global cerebral ischemia under normal-lipid condition, but was not effective on that under hyperlipidemic condition. 5. Polygoni Multiflori Radix was not effective on serum total-cholesterol, HDL-cholesterol, LDL-cholesterol and triglyceride levels under normal-lipid conditions, irrespective of focal cerebral infarct or global cerebral ischemia. 6. Polygoni Multiflori Radix significantly reduced the increase of serum total-cholesterol and triglyceride levels, and increased serum LDL-cholesterol level under hyperlipidemic conditions, irrespective of foc31 cerebral infarct or global cerebral ischemia.