• Animal cells and systems
• /
• 제12권4호
• /
• pp.211-217
• /
• 2008

Bax, a pro-apoptotic member of Bcl-2 family proteins, plays a central role in the mitochondria-dependent apoptosis. Apoptotic signals induce the translocation of Bax from cytosol into the mitochondria, which triggers the release of apoptogenic molecules such as cytochrome C and apoptosis-inducing factor, AIF. Bax-inhibiting peptide(BIP) is a cell permeable peptide comprised of five amino acids designed from the Bax-interaction domain of Ku70. Because BIP inhibits Bax translocation and Bax-mediated release of cytochrome C, BIP suppresses Bax-dependent apoptosis. In this study, we observed that BIP inhibited staurosporine-induced neuronal death in cultured cerebral cortex and cerebellar granule cells, but BIP failed to rescue granule cells from trophic signal deprivation-induced neuronal death, although both staurosporine-induced and trophic signal deprivation-induced neuronal death are dependent on Bax. These findings suggest that the mechanisms of the Bax activation may differ depending on the type of cell death induction, and thus BIP exhibits selective suppression of a subtype of Bax-dependent neuronal death.

• The Korean Journal of Physiology and Pharmacology
• /
• 제5권6호
• /
• pp.479-485
• /
• 2001

The existence of opioid receptors in mammalian cerebellum except human, has not been clearly understood. In the present study, we found that NPY was inducible by morphine in the mouse cerebellar granular and Purkinje cell layers. We performed in situ RT-PCR and immunohistochemistry to characterize the NPY expression. The increase of NPY gene expression by morphine (30 mg/kg, i.p.) was inhibited by pretreatment with not only naloxone (100 mg/kg, i.p.) but also a noncompetitive NMDA antagonist, MK-801 (0.3 mg/kg, i.p.). The competitive NMDA antagonist, AP-5 (0.9 mg/kg, i.p.) slightly attenuated the increased NPY expression by morphine. Also, the finding similar to morphine was shown by NMDA (70 mg/kg, i.p.) treatment. Our results indicate that NPY was inducible by morphine and this might reflect activation of NMDA receptors in granule cells that relay mossy fiber inputs to Purkinje cells via parallel fibers.

• Archives of Pharmacal Research
• /
• 제22권1호
• /
• pp.48-54
• /
• 1999

These studies were designed to examine the differential effect of nitric oxide (NO) and cGMP on glutamate neurotransmission. In primary cultures of rat cerebellar granule cells, the glutamate receptor agonist N-methyl-D-aspartate (NMDA) stimulates the elevation of intracellular calcium concentration ($[Ca^{2+}]_i$), the release of glutamate, the synthesis of NO and an increase of cGMP. Although NO has been shown to stimulate guanylyl cyclase, it is unclear yet whether NO alters the NMDA-induced glutamate release and ${[Ca^{2+}]}_i$ elevation. We showed that the NO synthase inhibitor, NG-monomethyl-L-arginine (NMMA), partially prevented the NMDA-induced release of glutamate and elevation of ${[Ca^{2+}]}_i$ and completely blocked the elevation of cGMP. These effects of NO on glutamate release and [Ca2+]i elevation were unlikely to be secondary to cGMP as the cGMP analogue, dibutyryl cGMP (dBcGMP), did not suppress the effects of NMDA. Rather, dBcGMP slightly augmented the NMDA-induced elevation of ${[Ca^{2+}]}_i$ with no change in the basal level of glutamate or ${[Ca^{2+}]}_i$. The extracellular NO scavenger hydroxocobalamine prevented the NMDA-induced release of glutamate providing indirect evidence that the effect of NO may act on the NMDA receptor. These results suggest that low concentration of NO has a role in maintaining the NMDA receptor activation in a cGMP-independent manner.

• 한국전문물리치료학회지
• /
• 제10권3호
• /
• pp.17-27
• /
• 2003

Repetitive transcranial magnetic stimulation (rTMS) modulates cortical excitability beyond the duration of the rTMS trains themselves. Depending on rTMS parameters, a lasting inhibition or facilitation of cortical excitability can be induced. Therefore, rTMS of high or low frequency over motor cortex may change certain aspects of motor learning performance and cortical activation. This study investigated the effect of high and low frequency subthreshold rTMS applied to the motor cortex on motor learning of sequential finger movements and brain activation using functional MRI (fMRI). Three healthy right-handed subjects (mean age 23.3) were enrolled. All subjects were trained with sequences of seven-digit rapid sequential finger movements, 30 minutes per day for 5 consecutive days using their left hand. 10 Hz (high frequency) and 1 Hz (low frequency) trains of rTMS with 80% of resting motor threshold and sham stimulation were applied for each subject during the period of motor learning. rTMS was delivered on the scalp over the right primary motor cortex using a figure-eight shaped coil and a Rapid(R) stimulator with two Booster Modules (Magstim Co. Ltd, UK). Functional MRI (fMRI) was performed on a 3T ISOL Forte scanner before and after training in all subjects (35 slices per one brain volume TR/TE = 3000/30 ms, Flip angle $60^{\circ}$, FOV 220 mm, $64{\times}64$ matrix, slice thickness 4 mm). Response time (RT) and target scores (TS) of sequential finger movements were monitored during the training period and fMRl scanning. All subjects showed decreased RT and increased TS which reflecting learning effects over the training session. The subject who received high frequency rTMS showed better performance in TS and RT than those of the subjects with low frequency or sham stimulation of rTMS. In fMRI, the subject who received high frequency rTMS showed increased activation of primary motor cortex, premotor, and medial cerebellar areas after the motor sequence learning after the training, but the subject with low frequency rTMS showed decreased activation in above areas. High frequency subthreshold rTMS on the motor cortex may facilitate the excitability of motor cortex and improve the performance of motor sequence learning in normal subject.

• Animal cells and systems
• /
• 제11권2호
• /
• pp.199-204
• /
• 2007

HCN (hyperpolarization-activated cyclic nucleotide-gated) channels, whose gene family consists of four subunits (HCN1-4), mediate depolarizing cation currents and contribute to controlling neuronal excitability. In the present study, immunohistochemical and electrophysiological approaches were used to elucidate the role of HCN channels in the cerebellum. Immunohistochemical labeling for HCN1 and HCN2 channels revealed localized expression of both channels at pinceau, the specialized structure of presynaptic axon terminals of basket cells. To determine the functional role of the presynaptic HCN channels, spontaneous inhibitory postsynaptic currents (IPSCs) were recorded from Purkinje cells, the main synaptic targets of basket cells in the cerebellum. While activation of HCN channels by 8-bromo-cAMP increased amplitude of spontaneous IPSCs, blockade of the activated HCN channels by subsequent ZD7288 application reduced the amplitude of spontaneous IPSCs to the level far below the control. Our results imply that modulation of HCN1 and HCN2 channels in presynaptic terminals of basket cells regulates neurotransmitter release, thereby controlling the excitability of Purkinje cells.

• Environmental Analysis Health and Toxicology
• /
• 제22권3호
• /
• pp.279-285
• /
• 2007

The present study attempted to analyze the mechanism of PCB-induced neurotoxicity with respect to the PKC signaling. Since the developing neuron is particularly sensitive to PCB-induced neurotoxicity, we isolated cerebellar granule cells derived from 7-day old SD rats and grew cells in culture for additional 7 days to mimic PND-14 conditions. Only non-coplanar PCBs at a high dose showed a significant increase of total PKC activity at $[^3H]PDBu$ binding assay, indicating that non-coplanar PCBs are more neuroactive than coplanar PCBs in neuronal cells. PKC isoforms were immunoblotted with respective monoclonal antibodies. PKC-alpha and-epsilon were activated with non-coplanar PCB exposure. The result suggests that coplanar PCBs have a PKC pathway different from non-coplanar PCBs. Activation of PKC with exposure was dampened with treatment of high molecular weight of chitosan. Chilean (M.W. > 1,000 kDa) inhibited the total activity of PKC induced by the non-coplanar PCBs. Translocation of PKC isoforms was also inhibited by the high molecular weight of chitosan. The study demonstrated that non-coplanar PCBs are more potent neurotoxic congeners than coplanar PCBs and the alteration of PKC activities by PCB exposure can be blocked with the treatment of chitosan. The results suggest a potential use of chitosan as a means of nutritional intervention to prevent the harmful effects of pollutant-derived diseases.

• BMB Reports
• /
• 제56권5호
• /
• pp.296-301
• /
• 2023

Retinoic acid receptor-related orphan receptor α (RORα) plays a vital role in various physiological processes, including metabolism, cancer, circadian rhythm, cerebellar development, and inflammation. Although RORα is expressed in the skin, its role in skin physiology remains poorly elucidated. Herein, Rorα was expressed in the basal and suprabasal layers of the epidermis; however, keratinocyte-specific Rorα deletion did not impact normal epidermal formation. Under pathophysiological conditions, Rorα-deficient mice exhibited alleviated psoriasis-like symptoms, including relatively intact epidermal stratification, reduced keratinocyte hyperproliferation, and low-level expression of inflammatory cytokines in keratinocytes. Unexpectedly, the splenic population of Th17 cells was significantly lower in keratinocyte-specific RORα deficient mice than in the control. Additionally, Rorα-deficiency reduced imiquimod-induced activation of nuclear factor-κB and STAT3 in keratinocytes. Therefore, we expect that RORα inhibitors act on immune cells and keratinocytes to suppress the onset and progression of psoriasis.

• Journal of Acupuncture Research
• /
• 제19권1호
• /
• pp.159-174
• /
• 2002

Objective : The meridian theory in oriental medicine explains that each acu-point has a characteristic functional effect. It will be supposed that an acupuncture stimulation on different acu-point evokes different activation on different areas in the central nervous system(CNS) according to the meridian theory. On this supposition, our group tried the semi-quantitative [14C]2-deoxyglucose([14C]2-DG) autoradiography on the acupuncture stimulation to the hindlimb acu-points of Sprague-Dawley rats. Methods : A venous catheter for the intravenous administration of isotope was equipped in the right external jugular vein on 3 days prior to the [14C]2-DG study. On the day of the study, two acupuncture needles were inserted into the ST36(Zusanli) or LR3(Taichong) on the left hindlimb. Electro-acupuncture stimulation (2 Hz, 5 ms, 1~3 mA, 15 minutes) started just before the i.v. injection of [14C]2-DG ($25{\mu}Ci/rat$). The brain and the spinal cord were removed and processed for the [14C] 2-DG autoradiography. Results : The EA stimulation on ST36 reveals over 120% metaboilc activation in Arcuate nucleus, Anterior pretectal nucleus, Dorsal cochlear nucleus, Interposed cerebellar nucleus, and Nucleus of Darkschewitsch. The EA stimulation on LR3 reveals over 120% metaboilc activation in Lateral habenula nucleus, Medial vestibular nucleus, Ventromedial thalamic nucleus, Anteroventral thalamic nucleus, Anterior cingulate cortex, Dentate gyrus, Antero cortical amygdaloid nucleus, Anterior pretectal nucleus, and Dorsal tegmental nucleus compared with the non EA stimulation control group. Conclusion : These results demonstrate that the different acu-points evoke the different activations in brain areas. And with this functional brain mapping study, a new scientific elucidation for the basis of the acupuncture-meridian theory in oriental medicine through differences of activated area in CNS according to the each acupuncture point.

• 수면정신생리
• /
• 제3권2호
• /
• pp.1-17
• /
• 1996

To demonstrate the clinical usefulness of electroencephalography (EEG) and factors increasing the usefulness of EEG, the authors evaluated each relationship between EEG related factors and clinical variables, and neuroimaging studies (CT and MRI)-related factors, and factors which are related with routine neurological examination for 207 patients who had been evaluated with both of EEG and neuroimaging study(CT or/and MRI). The results were as follows: 1) Abnormality of EEG findings had significant relationships with chief complaints, diagnosis, medication use, seizure attack, pathological reflex, and level of consciousness. However there were no significant correlations between abnormality of EEG findings and neuroimaging studies (CT and MRI)- related factors. 2) Laterality of EEG findings had significant relationships with abnormality, laterality, and focality of CT findings, and also with abnormality of MRI findings. But there were no significant correlations between laterality of EEG findings and clinical variables, and neurological examination-related factors. 3) Anterior-posterior distribution of EEG findings was significantly related with medication use. 4) Focality of EEG findings had significant relationships with sex, sensory dysfunction sign, and cerebellar dysfunction sign. But there were no significant correlations between focality of EEG findings and neuroimaging studies(CT and MRI) related factors. 5) Abnormal EEG pattern had significant correlations with various factors, such as age, chief complaints, duration from onset of symptom to taking MRI, seizure attack, abnormality and nature of lesion in CT findings, cortical atrophy in MRI findings, motor dysfunction sign, sensory dysfunction sign, and pathological reflex. 6) With abnormality on sleep activation, age, age of onset, seizure attack, ventricular enlargement in CT findings, and abnormality of MRI findings were significantly correlated. 7) With abnormality on hyperventilation activation, duration of illness and laterality of MRI findings were significantly correlated. Above results may suggest that abnormality of EEG findings is more closely related with functional change of the brain than structural changes of the brain and laterality of EEG findings is vice versa. And also that medication use has an influence on anterior versus posterior distribution of EEG findings and focality of EEG findings is not related with structural changes of the brain. Activation with sleep may be effective to show age differences and provocation of seizure activity and hyperventilation may be effective to detect the abnormal EEG findings by cerebrovascular insufficiency.

• 동의생리병리학회지
• /
• 제25권6호
• /
• pp.996-999
• /
• 2011

This experiment was performed to investigate whether the combined-preparation of crude drugs (The $Well^{TM}$ Preparation, TW), has hypnotic effects and/or enhances pentobarbital-induced sleep behaviors. TW was mixed with water extracts of Ginseng Radix red, Germinated brown rice, cultured mountain ginseng, and 50% ethanol extracts of Longanae Arillus, Nelumbinis Folium and Chrysanthemi Flos. TW (100 mg/kg, p.o.) reduced sleep onset and prolonged sleep time induced by pentobarbital similar to muscimol (0.2 ${\mu}M$), a $GABA_A$ receptor agonist. Also, TW (2 ${\mu}g$/ml) and pentobarbital (2.5 ${\mu}M$) did not affect the chloride influx in primary cultured cerebellar granule cells, respectively, but the combined-treatment of TW (2 ${\mu}g$/ml) and pentobarbital (2.5 ${\mu}M$) increased the chloride influx onto the cells. In conclusion, TW augments pentobarbital-induced sleep behaviors; these effects may result from chloride channel activation.