• Journal of Life Science
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• v.23 no.9
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• pp.1096-1103
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• 2013

Chronic traumatic encephalopathy (CTE), which is common in athletes, is a progressive neurodegenerative disease and a long-term consequence of repetitive closed head injuries. CTE is regarded as a chronic brain syndrome due to the effects of repetitive traumatic brain injury (TBI). Because neurotrophic factors are neuroprotective in models of brain and spinal cord injuries, we examined the effects of cerebrolysin, a mixture of various neurotrophic factors, on brain pathology in a mouse model of repetitive mild TBI (rmTBI), which is a good model of CTE. Five groups were created and treated as follows: groups 1 and 2: rmTBI for 4 weeks following cerebrolysin injection for 4 weeks; groups 3 and 4: rmTBI for 8 weeks with or without cerebrolysin injection for 4 weeks; group 5: control. We found that p-tau expression was increased in the pyramidal layer of the cortex and hippocampus, particularly the CA3 region, but not in the CA1 region and the dentate gyrus (DG). Intra-tail vein administration of cerebrolysin ($10{\mu}l$ of 1 mg/ml) after/during rmTBI treatment reduced p-tau expression in both the cortex and hippocampus. Histological analysis revealed mild astrocyte activation (increased expression of glial fibrillary acidic protein (GFAP)) but not microglia activation (ionized calcium binding adaptor molecule 1 (iba-1) expression) and peripheral macrophage infiltration (CD45). Additionally, administration of cerebrolysin after rmTBI resulted in reduced astrocyte activation. These observations in rmTBI demonstrated that cerebrolysin treatment reduces phosphorylation of tau and astrocyte activation, attenuates brain pathology, and mitigates function deficits in TBI. Taken together, our observations suggest that cerebrolysin has potential therapeutic value in CTE.

• Journal of the Korean Chemical Society
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• v.51 no.3
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• pp.251-257
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• 2007

The Tumor necrosis factor-α, (TNF-α), is involved in the pathogenesis of multiple sclerosis and contributes to the degeneration of oligodendrocytes as well as neurons. Nicotine has been found to have immunosuppressive and inflammation-suppressing effects. Astrocytes, the major glial cells in the CNS, are capable of producing TNF-α at both the mRNA and protein levels in response to interleukin-1 (IL-1) or TNF-α. Nicotine has been shown to influence glial cell functions. To order to explore the role of astrocytes in the production of TNF-α, astrocytes were pretreated with nicotine and are stimulated with IL-1β to determine their effects on TNF-α production. The results are as follows. Cytotoxic effects of nicotine on human fetal astrocytes were noted above 10 μg/ml of nicotine. The effect of IL-1β on TNF-α mRNA expression in primary cultured human fetal astrocytes was maximal at 2 h after IL- 1β(100 pg/ml) treatment. Human fetal astrocytes were pretreated with 0.1, 1, and 10 μg/ml of nicotine and then stimulated with IL-1β (100 pg/ml) for 2 h. The inhibitory effect of nicotine on expressions of TNF-α mRNA in human fetal astrocytes with pretreated 0.1 μg/ml of nicotine is first noted at 8 hr, and the inhibitory effect is maximal at 12 h. The inhibitory effect at 1 μg/ml of nicotine is inhibited maximal at 24 h. Nicotine at 0.1, 1 and 10 μg/ml concentrations significantly inhibits IL-1β-induced NF-κB activation. Collectively, this study indicates that nicotine might inhibit the expression of TNF-α in activated human fetal astrocytes.

• The Korea Journal of Herbology
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• v.36 no.6
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• pp.1-8
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• 2021

Objectives : Atractylodis rhizoma Alba has been traditionally used as a medicinal resource that is used for enhancing Qi (氣) in traditional medicine in Korea, China, and Japan. This study investigated the protective effects of Atractylodis rhizoma Alba extract (ARE) against trimethyltin (TMT), a neurotoxin that causes selective hippocampal injury, using both in vitro and in vivo models. Methods : We investigated the effects of ARE on TMT- (5mM) induced cytotoxicity in primary cultures of mouse hippocampal cells (7 days in vitro ) and on hippocampal injury in C57BL/6 mice injected with TMT (2.6 mg/kg). Results : We observed that ARE treatment (0 - 50 ㎍/mL) significantly reduced TMT-induced cytotoxicity in cultured hippocampal neurons in a dose-dependent manner, based on results of lactate dehydrogenase and 3-4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide assays. Additionally, this study showed that orally administered ARE (5 mg/kg; between -6 and 0 days before TMT injection) significantly attenuated seizures in adult mice. Furthermore, quantitative analysis of allograft inflammatory factor-1 (Iba-1)- and glial fibrillary acidic protein (GFAP)- positive cells showed significantly reduced levels of Iba-1- and GFAP-positive cell bodies in the dentate gyrus of mice treated with ARE prior to TMT injection. These findings indicate the significant protective effects of ARE against the TMT-induced massive activation of microglia and astrocytes in the hippocampus. Conclusions : We conclude that ARE minimizes the detrimental effects of TMT-induced hippocampal neurotoxicity, both in vitro and in vivo . Our findings may serve as useful guidelines to support ARE administration as a promising pharmacotherapeutic approach to hippocampal degeneration.

• Journal of Life Science
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• v.31 no.12
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• pp.1120-1127
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• 2021

Depression has a negative impact on social functioning due to its high prevalence and increased suicide rate, and is a disease with a high economic burden. Depression is related to diverse brain-related phenomena, such as neuroinflammation, synaptic dysfunction, and cognitive deficit. As antidepressant drugs used in clinical trials have shown poor therapeutic effects, antidepressant drugs that show rapid efficacy urgently need to be developed. Although studies on various genes, proteins, and signaling pathways related to depression have been conducted, the pathogenesis of depression has not been clearly elucidated. Sirtuin 1 is a nicotinamide-adenine dinucleotide- (NAD+-) dependent histone deacetylase and is involved in cell differentiation, apoptosis, autophagy, and cancer metabolism. Recent genetic studies found that sirtuin 1 is a potential target gene for depression. In addition, preclinical studies reported that sirtuin 1 signaling affects depression-like behavior. In this review, we attempt to present up-to-date knowledge of depression and sirtuin 1. We describe the various roles of sirtuin 1 in the regulation of glial activation, circadian rhythm, neurogenesis, and cognitive function and the effects of its expression on depression. Further, we discuss the effect of sirtuin 1 on the impairment of neural plasticity, one of the key mechanisms of depression, and the associated mechanisms of sirtuin 1.

• Applied Microscopy
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• v.35 no.3
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• pp.165-176
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• 2005

Studies on molecular plasticity of Bermann glia (BG) after harmaline-induced Purkinje cell (PC) degeneration in the rat cerebellum. The intimate structural relationship between BG and PC, evidenced by the sheathing of the PC dendrites by veil-like process from the BG has been suggestive of the close functional relationship between these two cell types. However, little is known about metabolic couplings between these cells. This study designed to investigate molecular plasticity of BG in the rat cerebellum in which PCs were chemically ablated by harmaline treatment. Immunohistochemical examination reveals that harmaline induced PC degeneration causes a marked glial reaction in the cerebellum with activated BG and microglia aligned in parasagittal stripes within the vermis. In these strips, activated BG were associated with upregulaion of metallotheionein, while GLAST and was down regulated, as compared with nearby intact area where both BG are in contact with PCs. The data from this study demonstrate that BG can change their phenotypic expression when BG loose their contact with PCs. It is conceivable that activated BG may upregulate structural proteins, metallothionein expression to use for their proliferation and hypertrophy; metallothionein expression to cope with oxidative stress induced by PC degeneration and microglial activation. On the contrary, BG may down regulated expression of GLAST because sustained loss of contact with PCs would eliminate the necessity for the cellular machinery involved glutamate metabolism. In conclusion, BG might respond man to death of PCs by undergoing a change in metabolic state. It seems possible that signaling molecules released from PCs regulates the phenotype expression of BG. Also ultrastructures in the organelles of normal PC and BG are distinguished by mitochondrial appearance, and distributed vesicles at the synaptic area in the cytoplasm.