• 생물정신의학
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• 제30권1호
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• pp.1-6
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• 2023

Many psychiatric disorders are associated with brain functional dysfunctions and neuronal degeneration. According to the research so far, enhanced brain plasticity reduces neurodegeneration and recovers neuronal damage. Brain-derived neurotrophic factor (BDNF) is one of the most extensively studied neurotrophins in the mammalian brain that plays major roles in neuronal survival, development, growth, and maintenance of neurons in brain circuits related to emotion and cognitive function. Also, BDNF plays an important role in brain plasticity, influencing dendritic spines in the hippocampus neurogenesis. Changes in neurogenesis and dendritic density can improve psychiatric symptoms and cognitive functions. BDNF has potent effects on brain plasticity through biochemical mechanisms, cellular signal pathways, and epigenetic changes. There are pharmacological and non-pharmacological interventions to increase the expression of BDNF and enhance brain plasticity. Non-pharmacological interventions such as physical exercise, nutritional change, environmental enrichment, and neuromodulation have biological mechanisms that increase the expression of BDNF and brain plasticity. Non-pharmacological interventions are cost-effective and safe ways to improve psychiatric symptoms.

• 한방재활의학과학회지
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• 제21권2호
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• pp.143-158
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• 2011

Objectives : Peripheral nerve injuries are commonly encountered clinical problem and often result in severe functional deficits. The aim of this study is to evaluate the effects of aqueous extract of Achyranthes japonica(AJ) on functional recovery in sciatic nerve after crushed sciatic nerve injury. Methods : In the present study, the animals in the AJ-treated groups received the aqueous extract of AJ at the respective doses orally for 13 consecutive days. In order to assess the effects of the aqueous extract of AJ on function recovery in crushed sciatic nerve injury, sciatic functional index(SFI) was performed. c-Fos expression in the paraventricular nucleus(PVN) and ventrolateral periaqueductal gray(vIPAG), and neurofilament, and the expressions of brain-derived neurotrophic factor(BDNF), nerve growth factor(NGF) following crushed sciatic nerve injury in rats were investigated. For this, immunohistochemistry and western blot were performed. Results : In the present study, crushed sciatic nerve injury showed characteristic gait changes showing decrease of SFI value and treatment with the aqueous extract of AJ significantly enhanced the SFI value. Neurofilament expression in the sciatic nerve was decreased by crushed sciatic nerve injury and treatment with the AJ increased neurofilament expression. The expressions of BDNF and NGF in the sciatic nerve were increased following crushed sciatic nerve injury and treatment with the AJ significantly controlled the sciatic nerve injury-induced increment of BDNF and NGF expressions. c-Fos expressions in the PVN and vIPAG were increased following crushed sciatic nerve injury and treatment with the AJ significantly suppressed the sciatic nerve injury-induced increment of c-Fos expressions. Conclusions : These results suggest that AJ treatment after crushed sciatic nerve injury is effective in the functional recovery by enhancing axonal regeneration and suppressing of pain.

• Molecules and Cells
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• 제21권2호
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• pp.237-243
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• 2006

Brain-derived neurotrophic factor (BDNF) is a neuromodulator of nociceptive responses in the dorsal root ganglia (DRG) and spinal cord. BDNF synthesis increases in response to nerve growth factor (NGF) in trkA-expressing small and medium-sized DRG neurons after inflammation. Previously we demonstrated differential activation of multiple BDNF promoters in the DRG following peripheral nerve injury and inflammation. Using reporter constructs containing individual promoter regions, we investigated the effect of NGF on the multiple BDNF promoters, and the signaling pathway by which NGF activates these promoters in PC12 cells. Although all the promoters were activated 2.4-7.1-fold by NGF treatment, promoter IV gave the greatest induction. The p38 mitogen-activated protein kinase (MAPK) inhibitor, SB203580, phosphatidylinositol 3-kinase (PI-3K) inhibitor, LY294003, protein kinase A (PKA) inhibitor, H89, and protein kinase C (PKC) inhibitor, chelerythrine, had no effect on activation of promoter IV by NGF. However, activation was completely abolished by the MAPK kinase (MEK) inhibitors, U0126 and PD98059. In addition, these inhibitors blocked NGF-induced phosphorylation of extracellular signal-regulated protein kinase (ERK) 1/2. Taken together, these results suggest that the ERK1/2 pathway activates BDNF promoter IV in response to NGF independently of NGF-activated signaling pathways involving PKA and PKC.

• 대한임상검사과학회지
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• 제52권4호
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• pp.417-424
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• 2020

이 연구는 신경인성 방광 쥐 모델에서 줄기세포에 의해 발현된 뇌유래신경영양인자가 하부요로 증상에 미치는 영향을 조사하였다. 48마리의 Sprague-Dawley 쥐를 정상군, 하부요로증상군, 하부요로증상+imMSC군 및 하부요로증상+BDNF-eMSC군으로 무작위 선정하였다. 하부요로증상모델은 골반신경절 손상에 의해 유도되었으며 방광 기능평가는 마취 하에 실시하였고, 수축성 검사 및 웨스턴 블롯 분석을 위해 방광 조직을 절제하였다. 뇌유래신경영양인자 발현 중간엽줄기세포 치료가 하부요로증상에 미치는 영향도 평가되었으며 뇌유래신경영양인자 발현 중간엽줄기세포는 방광 조직의 섬유화를 억제하였고 Caspase-3 발현을 감소시켰다. 결론적으로, 뇌유래신경영양인자 발현 중간엽줄기세포는 하부요로증상 쥐 모델에서 세포 사멸의 억제와 함께 방광의 기능 및 수축성의 회복을 가져왔다.

• The Korean Journal of Physiology and Pharmacology
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• 제24권1호
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• pp.27-37
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• 2020

Neuroinflammation is an important process underlying a wide variety of 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 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 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 memory impairment caused by neuroinflammation. This cognitive enhancement is due to the anti-inflammatory effects of CAR medicated by its regulation of BDNF and TLR4. Thus, CAR has significant potential as an inhibitor of memory degeneration in neurodegenerative diseases.

• The Korean Journal of Pain
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• 제11권2호
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• pp.182-193
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• 1998

Background: Ciliary neurotrophic factor (CNTF), identified as a survival factor for developing peripheral neurons is upregulated by reactive astrocytes in the traumatized tissue and in areas of terminal degeneration after a brain lesion. But in the spinal cord, CNTF is expressed in the non-astrocytic phenotypic, maybe oligodendrocytes. The present study was undertaken to determine the upregulation of CNTF expression in reactive astrocytes following spinal cord lesion in the rat. Methods: Unilateral incision of the dorsal funiculus at the thoracic level was performed and rats were sacrificed on days 3, 7, 14 and 28 postlesion. Western blot analysis, immunocytochemical analysis and double immunofluorescence for CNTF and glial fibrillary acidic protein (GFAP) were performed after spinal cord lesion. Results: A major band with 24 kDa and additional band of higher molecular weight form were detectable, and the intensity of the 24 kDa immunoreactive band increased up to 14 days postlesion and decreased toward laminectomized control values. CNTF immunoreactivity was markedly upregulated in the injured dorsal funiculus and adjacent gray matter. The time course of CNTF expression is coincident with the appearance of reactive astrocytes in the injured spinal cord. Moreover, double immunofluorescence for CNTF and glial fibrillary acidic protein (GFAP) revealed that CNTF immunoreactivity was in GFAP immunoreactive astrocytes. Conclusions: These results show that CNTF upregulation occurred in reactive astrocytes following spinal cord lesion, and suggest a role for CNTF in the regulation of astrocytic responses after spinal cord injury.

• The Korean Journal of Physiology and Pharmacology
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• 제16권2호
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• pp.79-89
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• 2012

We examine whether Phellodendron amurense (PA) and its major alkaloid compound, berberine (BER), improved memory defects caused by administering scopolamine in rats. Effects of PA and BER on the acetylcholinergic system and pro-inflammatory cytokines in the hippocampus were also investigated. Male rats were administered daily doses for 14 days of PA (100 and 200 mg/kg, i.p.) and BER (20 mg/kg, i.p.) 30 min before scopolamine injection (2 mg/kg, i.p.). Daily administration of PA and BER improved memory impairment as measured by the passive avoidance test and reduced the escape latency for finding the platform in the Morris water maze test. Administration of PA and BER significantly alleviated memory-associated decreases in cholinergic immunoreactivity and restored brain-derived neurotrophic factor and cAMP-response element-binding protein mRNA expression in the hippocampus. PA and BER also decreased significantly the expression of proinflammatory cytokines such as interleukin-$1{\beta}$, tumor necrosis factor-${\alpha}$ and cyclooxygenase-2 mRNA in the hippocampus. These results demonstrated that PA and BER had significant neuroprotective effects against neuronal impairment and memory dysfunction caused by scopolamine in rats. These results suggest that PA and BER may be useful as therapeutic agents for improving cognitive functioning by stimulating cholinergic enzyme activity and alleviating inflammatory responses.

• The Korean Journal of Physiology and Pharmacology
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• 제18권3호
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• pp.191-200
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• 2014

We investigated the anxiolytic-like activity of ${\alpha}$-asarone (AAS) from Acorus gramineus in an experimental rat model of anxiety induced by repeated administration of the exogenous stress hormone corticosterone (CORT). The putative anxiolytic effect of AAS was studied in behavioral tests of anxiety, such as the elevated plus maze (EPM) test and the hole-board test (HBT) in rats. For 21 consecutive days, male rats received 50, 100, or 200 mg/kg AAS (i.p.) 30 min prior to a daily injection of CORT. Dysregulation of the HPA axis in response to the repeated CORT injections was confirmed by measuring serum levels of CORT and the expression of corticotrophin-releasing factor (CRF) in the hypothalamus. Daily AAS (200 mg/kg) administration increased open-arm exploration significantly in the EPM test, and it increased the duration of head dipping activity in the HBT. It also blocked the increase in tyrosine hydroxylase (TH) expression in the locus coeruleus (LC) and decreased mRNA expression of brain-derived neurotrophic factor (BDNF) and its receptor, TrkB, in the hippocampus. These results indicated that the administration of AAS prior to high-dose exogenous CORT significantly improved anxiety-like behaviors, which are associated with modification of the central noradrenergic system and with BDNF function in rats. The current finding may improve understanding of the neurobiological mechanisms responsible for changes in emotions induced by repeated administration of high doses of CORT or by elevated levels of hormones associated with chronic stress. Thus, AAS did exhibit an anxiolytic-like effects in animal models of anxiety.

• 동의신경정신과학회지
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• 제33권3호
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• pp.277-285
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• 2022

Objectives: Gastrodia elata (GE) has been used to treat cognition impairment, including Alzheimer's disease (AD) in Korea. The purpose of this study was to investigate the effects of GE water extracts (GEE) on the lipopolysaccharide (LPS)-induced AD model in mice. (Aβ). Methods: We classified six groups as follow; group 1: control (CON), group 2: LPS (0.5 mg/kg/day, four times), group 3: 4 mg/kg donepezil (DP), group 4: 100 mg/kg GEE+LPS, group 5: 200 mg/kg GEE+LPS, group 6: 500 mg/kg GEE+LPS. Results: We found that GEE has an effect that inhibits decrease of discrimination index in object recognition test, as well as spontaneous alteration in the Y-maze test by LPS. Treatment with LPS increased amlyloid-β (Aβ) concentration, and decreased brain-derived neurotrophic factor (BDNF) in cerebral cortex of mice. However, GEE significantly protected against LPS-induced Aβ and BDNF changes. Our findings also showed that the inflammatory cytokines [tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β)] mRNA and protein were up-regulated by the LPS injection. But GEE significantly suppressed LPS-induced inflammatory cytokines increase in a dose-dependent manner. Conclusions: This study suggests that the GEE may be an effective AD therapeutic agent, in treating neurodegenerative diseases including AD.

• Anatomy and Cell Biology
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• 제57권1호
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• pp.70-84
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• 2024

Methamphetamine (METH) can potentially disrupt neurotransmitters activities in the central nervous system (CNS) and cause neurotoxicity through various pathways. These pathways include increased production of reactive nitrogen and oxygen species, hypothermia, and induction of mitochondrial apoptosis. In this study, we investigated the long-term effects of METH addiction on the structural changes in the amygdala of postmortem human brains and the involvement of the brain- cAMP response element-binding protein/brain-derived neurotrophic factor (CREB/BDNF) and Akt-1/GSK3 signaling pathways. We examined ten male postmortem brains, comparing control subjects with chronic METH users, using immunohistochemistry, real-time polymerase chain reaction (to measure levels of CREB, BDNF, Akt-1, GSK3, and tumor necrosis factor-α [TNF-α]), Tunnel assay, stereology, and assays for reactive oxygen species (ROS), glutathione disulfide (GSSG), and glutathione peroxidase (GPX). The findings revealed that METH significantly reduced the expression of BDNF, CREB, Akt-1, and GPX while increasing the levels of GSSG, ROS, RIPK3, GSK3, and TNF-α. Furthermore, METH-induced inflammation and neurodegeneration in the amygdala, with ROS production mediated by the CREB/BDNF and Akt-1/GSK3 signaling pathways.