• Proceedings of the Korean Society of Applied Pharmacology
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• 2000.04a
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• pp.15-16
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• 2000

Transient forebrain ischemia results in delayed neuronal death in the CA1 region of the hippocampus after injury, which is, at least in part, a consequence of excessive generation of reactive oxygen species. Previous in vitro studies using cell cultures or brain slices have demonstrated that phospholipase D (PLD) in the nervous system is involved in the signaling mechanism in response to a variety of agonists. Several recent studies have shown that reactive oxygen species stimulate phospholipase D (PLD) activity in several kinds of cells. Therefore, this raises the possibility that PLD activity is enhanced in the ischemic brain. Meanwhile, osteopontin (OPN) was initially identified as a sialoglycoprotein in bone, but has since been found in various tissues. Although not much is known about its function, OPN seems to play an important role in inflammation and tissue repair. Recently, it was reported that OPN was upregulated in the activated microglia after focal brain ischemia, suggesting that OPN might play a role in wound healing after a focal stroke.

• BMB Reports
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• v.42 no.5
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• pp.239-244
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• 2009

New neurons are continually generated in the subgranular zone of the dentate gyrus and in the subventricular zone of the lateral ventricles of the adult brain. These neurons proliferate, differentiate, and become integrated into neuronal circuits, but how they are involved in brain function remains unknown. A deficit of adult hippocampal neurogenesis leads to defective spatial learning and memory, and the hippocampi in neuropsychiatric diseases show altered neurogenic patterns. Adult hippocampal neurogenesis is not only affected by external stimuli but also regulated by internal growth factors including BDNF, VEGF and IGF-1. These factors are implicated in a broad spectrum of pathophysiological changes in the human brain. Elucidation of the roles of such neurotropic factors should provide insight into how adult hippocampal neurogenesis is related to psychiatric disease and synaptic plasticity.

• Journal of Microbiology and Biotechnology
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• v.23 no.12
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• pp.1779-1784
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• 2013

Although enzyme-hydrolyzed silk fibroin has been reported to enhance cognitive function before, it has been still unknown which peptides can improve memory. Here we report that amino acid sequences of three novel peptides were identified from fibroin hydrolysate. Fibroin hydrolysate was obtained by hydrolysis with protease after partial hydrolysis with 5M $CaCl_2$. Synthesized peptides derived from these sequences improved scopolamine-induced memory impairments in mice. We confirmed this hydrolysate had effects that improved learning and memory abilities by performing the Rey-Kim test. From this hydrolysate of silk fibroin, amino acid sequences of eight peptides were identified by LC-MS/MS. Three peptides (GAGAGTGSSGFGPY, GAGAGSGAGSGAGAGSGAGAGY, and SGAGSGAGAGSGAGAGSGA) were synthesized to investigate whether they could improve memory. Passive avoidance test and Morris water maze test were performed, and all peptides showed memory-enhancing abilities on scopolamine-induced memory impairments in mice. In this study, we identified three novel peptides that could improve memory, and that silk fibroin hydrolysate was a mixture of various active peptides that could enhance memory.

• Journal of Microbiology and Biotechnology
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• v.15 no.2
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• pp.451-454
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• 2005

Introduction of foreign genes into brain cells, such as neurons and astrocytes, is a powerful approach to study the gene function and regulation in the neuroscience field. Calcium phosphate precipitates have been shown to cause cytotoxicity in some mammalian cells and brain cells, thus leading to low transfection efficiency. Here, we describe a retrovirus-mediated gene delivery method to transduce foreign genes into brain cells. In an attempt to achieve higher gene delivery efficiency in these cells, we made several changes to the original method, including (1) use of a new packaging cell line, Phoenix ampho cells, (2) transfection of pMX retroviral DNA, (3) inclusion of 25 mM chloroquine in the transduction, and (4) 3- 5 h incubation of retroviruses with target cells. The results showed that the modified protocol resulted in a range of 40- 60% gene delivery efficiency in neurons and astrocytes. Furthermore, these results suggest the potential of the retrovirus-mediated gene delivery protocol being modified and adapted for other transfection-refractory cell lines and primary cells.

• BMB Reports
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• v.54 no.3
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• pp.149-156
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• 2021

The well-known second messenger cyclic adenosine monophosphate (cAMP) regulates the morphology and physiology of neurons and thus higher cognitive brain functions. The discovery of exchange protein activated by cAMP (Epac) as a guanine nucleotide exchange factor for Rap GTPases has shed light on protein kinase A (PKA)-independent functions of cAMP signaling in neural tissues. Studies of cAMP-Epac-mediated signaling in neurons under normal and disease conditions also revealed its diverse contributions to neurodevelopment, synaptic remodeling, and neurotransmitter release, as well as learning, memory, and emotion. In this mini-review, the various roles of Epac isoforms, including Epac1 and Epac2, highly expressed in neural tissues are summarized, and controversies or issues are highlighted that need to be resolved to uncover the critical functions of Epac in neural tissues and the potential for a new therapeutic target of mental disorders.

• Anatomy and Cell Biology
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• v.57 no.2
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• pp.155-162
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• 2024

Cerebral ischemia is the important cause of worldwide disability and mortality, that is one of the obstruction of blood vessels supplying to the brain. In early stage, glutamate excitotoxicity and high level of intracellular calcium (Ca²⁺) are the major processes which can promote many downstream signaling involving in neuronal death and brain tissue damaging. Moreover, autophagy, the reusing of damaged cell organelles, is affected in early ischemia. Under ischemic conditions, autophagy plays an important role to maintain energy of the brain and its function. In the other hand, over intracellular Ca²⁺ accumulation triggers excessive autophagic process and lysosomal degradation leading to autophagic process impairment which finally induce neuronal death. This article reviews the association between intracellular Ca²⁺ and autophagic process in acute stage of ischemic stroke.

• Journal of Life Science
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• v.19 no.10
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• pp.1417-1423
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• 2009

Previous studies have suggested that docosahexaenoic acid (DHA) supplementation into n-3 fatty acid deficient diet improved spatial learning performance, but there was no significant difference in brain related function when DHA was added into a n-3 fatty acid adequate diet. Here, we investigated the effect of adding DHA into an n-3 fatty acid deficient or adequate diet on brain and liver fatty acid composition. On the second day after conception, Sprague Dawley strain dams were divided into four groups as follows; n-3 fatty acid deficient (Def), n-3 fatty acid deficient plus DHA (Def+DHA, 10.2% DHA), n-3 fatty acid adequate (Adq, 3.4% linolenic acid), and n-3 fatty acid adequate plus DHA (Adq+DHA, 3.31% linolenic acid plus 9.65% DHA). After weaning, male pups were fed on the same diets of their respective dams until adulthood. In brain fatty acid composition, the Def group showed a lower brain DHA (64% decrease), which was largely compensated for by an increase in docosapentaenoic acid (22:5n-6). Brain DHA in the Def+DHA group was increased to almost the same extent as in the Adq and Adq+DHA groups and there were no significant differences among them. Liver fatty acid composition showed a similar pattern to that of the brain, but liver DHA in the Def+DHA showed the highest percentage among the diet groups. In conclusion, n-3 fatty acid deficiency from gestation to adulthood leads to decreased brain DHA, which has been shown to be highly associated with poor spatial leaning performance. Thus, adequate brain DHA levels are required for optimal nervous function.

• The Journal of Korean Physical Therapy
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• v.24 no.6
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• pp.423-427
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• 2012

Purpose: The cerebellum is a region of brain structure that plays an important role in calibrating two different information of neural signal from descending motor commands and from ascending sensory inputs. Damage of the cerebellum shows a variety of classic motor symptoms such as postural and locomotor dysfunctions. Therefore, we tried to investigate motor function and skill in stroke patients with cerebellar lesions in sub-acute stage, and compare with these functions of patients with non-cerebellar lesions. Methods: Total twelve stroke patients with cerebellar lesion and 130 stroke patients with non-cerebellar lesions were retrospectively recruited in this study. For evaluation of motor strength, Motricity index (MI) for upper and lower limbs was tested. For measurement of motor skill function, the modified Brunnstrom classification (MBC), Manual function test (MFT), functional ambulatory category (FAC), and Barthel index were adopted. Results: In comparison of motor strength and motor skill function between two groups, statistical differences between the two groups were significantly observed only in upper MI and FAC. Although no significant differences were found in other variables, stroke patients with cerebellar lesion had higher scores in lower and total MI, MBC, and MFT, whereas they had lower scores in FAC and Barthel index. Conclusion: Our results showed that stroke patients with cerebellar lesion had greater impact on movement functions related to hand motor and walking ability in activities of daily life, compared with patients with non-cerebellar lesion, in spite of similar degree of motor function and skill between the two different lesioned-groups.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.4
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• pp.425-432
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• 2016

In addition to classical synaptic transmission, information is transmitted between cells via the activation of extrasynaptic receptors that generate persistent tonic current in the brain. While growing evidence supports the presence of tonic NMDA current ($I_{NMDA}$) generated by extrasynaptic NMDA receptors (eNMDARs), the functional significance of tonic $I_{NMDA}$ in various brain regions remains poorly understood. Here, we demonstrate that activation of eNMDARs that generate INMDA facilitates the ${\alpha}$-amino-3-hydroxy-5-methylisoxazole-4-proprionate receptor (AMPAR)-mediated steady-state current in supraoptic nucleus (SON) magnocellular neurosecretory cells (MNCs). In $low-Mg^{2+}$ artificial cerebrospinal fluid (aCSF), glutamate induced an inward shift in $I_{holding}$ ($I_{GLU}$) at a holding potential ($V_{holding}$) of -70 mV which was partly blocked by an AMPAR antagonist, NBQX. NBQX-sensitive $I_{GLU}$ was observed even in normal aCSF at $V_{holding}$ of -40 mV or -20 mV. $I_{GLU}$ was completely abolished by pretreatment with an NMDAR blocker, AP5, under all tested conditions. AMPA induced a reproducible inward shift in $I_{holding}$ ($I_{AMPA}$) in SON MNCs. Pretreatment with AP5 attenuated $I_{AMPA}$ amplitudes to ~60% of the control levels in $low-Mg^{2+}$ aCSF, but not in normal aCSF at $V_{holding}$ of -70 mV. $I_{AMPA}$ attenuation by AP5 was also prominent in normal aCSF at depolarized holding potentials. Memantine, an eNMDAR blocker, mimicked the AP5-induced $I_{AMPA}$ attenuation in SON MNCs. Finally, chronic dehydration did not affect $I_{AMPA}$ attenuation by AP5 in the neurons. These results suggest that tonic $I_{NMDA}$, mediated by eNMDAR, facilitates AMPAR function, changing the postsynaptic response to its agonists in normal and osmotically challenged SON MNCs.

• BMB Reports
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• v.49 no.11
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• pp.587-589
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• 2016

The circadian clock system enables organisms to anticipate the rhythmic environmental changes and to manifest behavior and physiology at advantageous times of the day. Transcriptional/translational feedback loop (TTFL) is the basic feature of the eukaryotic circadian clock and is based on the rhythmic association of circadian transcriptional activator and repressor. In Drosophila, repression of dCLOCK/CYCLE (dCLK/CYC) mediated transcription by PERIOD (PER) is critical for inducing circadian rhythms of gene expression. Pacemaker neurons in the brain control specific circadian behaviors upon environmental timing cues such as light and temperature cycle. We show that amino acids 657-707 of dCLK are important for the transcriptional activation and the association with PER both in vitro and in vivo. Flies expressing dCLK lacking AA657-707 in $Clk^{out}$ genetic background, homologous to the mouse Clock allele where exon 19 region is deleted, display pacemaker-neuron-dependent perturbation of the molecular clockwork. The molecular rhythms in light-cycle-sensitive pacemaker neurons such as ventral lateral neurons ($LN_vs$) were significantly disrupted, but those in temperature-cycle-sensitive pacemaker neurons such as dorsal neurons (DNs) were robust. Our results suggest that the dCLK-controlled TTFL diversify in a pacemaker-neuron-dependent manner which may contribute to specific functions such as different sensitivities to entraining cues.