Research progress on the role of circular RNA in neonatal hypoxic-ischemic encephalopathy / 中国临床药理学与治疗学

Hypoxic-ischemic encephalopathy (HIE) is a major cause of newborn mortality and childhood disability. Despite hypothermia treatment being the current standard method, it has its limitations and often produces unsatisfactory outcomes. Additionally, due to time and equipment constraints, hypothermia treatment cannot be promptly administered, leading to high mortality rates or varying levels of neurological impairments even after treatment. Hence, the exploration of alternative and effective treatment methods for HIE has become a challenging and highly researched topic in the field of neonatology. Research has shown that HIE induces intricate changes in the neurological system at the physiological, cellular, and molecular levels. Circular RNA (circRNA) exhibits high expression in the central nervous system and plays a role in regulating physiological and pathophysiological processes. Therefore, circRNA holds promise as a potential therapeutic target for HIE. This article provides a comprehensive overview of the regulatory effects of circRNA on different types of neural cells in HIE, aiming to offer new theoretical foundations for the treatment of HIE.

Construction of Ndfip1 plasmid and its expression in neuroblastoma SH-SY5Y cells / 吉林大学学报(医学版)

Objective::To observe the expression of divalent metal transporter 1 (DMT1) in neurons under the condition of Ndfip1 overexpression, and to explore the regulation effect of Ndfip1 on DMT1. Methods:The Ndfip1 eukaryotic expression plasmid was constructed, and the human neuroblastoma SH-SY5Y cells were transfected with Ndfip1 plasmid; the transfection efficiency was detected. The SH-SY5Y cells transfected with Ndfip1 plasmid were used as experimental group,and the SH-SY5Y cells transfected with empty plasmid were used as control group. The expression intensities of DMT1 protein in the SH-SY5Y cells in two groups were observed by immunofluorescence method,and the expression levels of DMT1 protein in the SH-SY5Y cells in two groups were detected by Western blotting method. Results:The plasmid was amplified, electrophoretically separated and sequenced, and the results proved that the plasmid was successfully constructed. After transfection of SH-SY5Y cells with Ndfip1 plasmid for 48 h, the expression level of Ndfip1 was significantly increased compared with before transfection (P<0.01). The immunofluorescence results showed that the fluorescence intensity of DMT1 in the cells in experimental group was significantly decreased compared with control group. The Western blotting results showed that the expression level of DMT1 in the cells in experimental group was decreased (P<0.05) compared with control group. Conclusion:The overexpression of Ndfip1 can down-regulate the expression of DMT1 protein in the nerve cells, and Ndfip1 nerve has a negatively regulatory effect.

Research process in synergistic induction of neuronal autophagy by methamphetamine and HIV-1 Tat protein / 中国药理学通报

Methamphetamine (METH) abuse and HIV infection are serious public health and social issues in the current world. Autophagy is a process in which vesicles derived from endoplasmic reticulum package abnormal proteins and damaged organelles to form autophagosomes and transport them to lysosomes for degradation. Both METH and HIV-1 Tat protein can induce autophagy in nerve cells, therefore, in this review, the research process of neuronal autophagy induced by METH and HIV-lTat protien were summarized, and the interaction of METH, HIV-lTat protein, and autophagy were explored, so as to provide reference for searching for effective drug intervention targets.

Mechanobiological Response and Network Formation in Central Nervous Development / 医用生物力学

In the process of central nervous system (CNS) development and maturation, the biomechanical factors have not been highly valued for a long time. In recent years, a large number of studies have shown that mechanical environment strongly affects the migration, differentiation and maturation of nerve cells, as well as the cell-cell interactions. Mechanical factors play an important role in realization of the structure and function of the brain and spinal cord. This review briefly summarized the role of biomechanics in CNS perception, path-finding, regulation and network shaping during CNS development. The effects of static and dynamic mechanics on mechanobiological response of nerve cells were also introduced, hoping to provide some ideas for CNS reconstruction and repair in future.

Urban PM2.5 in Guangzhou induces apoptosis of PC-12 cells / 实用医学杂志

Objective To investigate the toxicity of urban PM2.5 in Guangzhou on PC-12 cells.Methods PM2.5 was collected in Guangzhou city.PC-12 cells were cultured in vitro and divided into several groups,including the control group,PM2.5 groups with different concentrations and NAC pretreated group (pretreaed with 10 μmol/mL NAC followed with 100 μg/mL PM2.5 exposure).Cells were incubated with indicated stimulator for 24 h,then cell viability was checked with cell counting Kit-8 assay,the level of intracellular ROS was labeled using H2DCFDA fluorescence probe,cell apoptosis was measured by the flow cytometry and the expression of apoptosis-related proteins,including Cytochrome C,Caspase 9,Caspase 3 and PARP,were detected by Western Blot assay.Results PM2.5 has a strong toxicity on PC-12 cells when its concentration is over 25 μg/mL.After exposure for 24 h,the cell viability was markedly decreased.The results of flow cytometry and Western blot assay showed that PM2.5 enhanced the apoptosis of PC-12 cells with the upregulatios of Cytochrome C,Caspase 9,Caspase 3 and PARP.Pretreatment with NAC could significantly diminish PM2.5-induced PC-12 cell toxicity,decreased ROS generation and apoptosis of PC-12 cells,with the down regulations of apoptosis-related proteins.Conclusion PM2.5 can cause apoptosis of PC-12 cells by inducing oxidative stress,upregulating the Cytochrome C expression and activating Caspase9/3,which may be one of the mechanisms underlying PM2.5-induced neurotoxicity.

Protective effect of BAG-1L mediated by lentivirus in human neuroblastoma cells induced by hypoxia / 中华危重病急救医学

Objective To investigate the protective effects of lentivirus mediated Bcl-2-associated athanogene 1L (BAG-1L) over-expression on human neuroblastoma cells (SH-SYSY) induced by hypoxia/re-oxygenation,and to study its effect on the phosphoinositide 3 kinase serine/threonine protein kinase (PI3K/AKT) pathway.Methods SH-SYSY cells were cultured in vitro,and the cells at logarithmic phase were collected,and they were divided into recombined lentiviral infection group [infected by lentivirus containing BAG-1L and green fluorescent protein (GFP) gene],vector control group (infected by lentivirus containing GFP without BAG-1L gene) and cell control group (non-infection).Western Blot was used to detect the expression of BAG-1L in target cells after infection for 48 hours.SH-SY5Y cells were subjected to hypoxia for 8 hours and re-oxygenation for 24 hours,then the cell counting kit-8(CCK-8) was used to detect the cell activity,and the apoptosis was detected by flow cytometry after allophycocyanin labeled annexin V/7-amino actinomycin D (Annexin V-APC/7-AAD) staining.Western Blot was used to detect the protein expressions of BAG-1L,heat shock protein 70 (HSP70),AKT and phosphorylated AKT (p-AKT).Results After infection for 48 hours,exogenous BAG-1L protein bands were observed in recombined lentiviral infection group,but not observed in cell control group and vector control group.After hypoxia/re-oxygenation treatment,the cell viability in recombined lentiviral infection group was significantly higher than that in cell control group and vector control group (A value:0.689 ± 0.036 vs.0.425 ± 0.013,0.400 ± 0.012),apoptosis was significantly decreased [apoptosis rate:(26.97 ± 1.82)％ vs.(36.60± 1.45)％,(35.77 ± 3.74)％],the protein levels of BAG-1L,HSP70 and p-AKT were significantly increased [BAG-1L protein (gray value):2.405 ± 0.167 vs.0.529 ± 0.141,0.601 ± 0.099;HSP70protein (gray value):0.997±0.123 vs.0.634±0.091,0.584±0.106;p-AKT protein (gray value):1.234±0.118 vs.0.661 ± 0.210,0.712 ± 0.199,all P ＜ 0.01],but the protein level of AKT was slightly increased (gray value:1.103 ± 0.269vs.0.646 ± 0.188,0.791 ± 0.326) without statistically significant differences (both P ＞ 0.05).There was no significant difference in all parameters between cell control group and vector control group (all P ＞ 0.05).Conclusion Lentivirus mediated BAG-1L gene over-expression can protect nerve cells against hypoxic injury and apoptosis,and the protective effect may be related to the activation increase of pathway on PI3K/AKT.

Protective Effect of Mullein Glycoside Polysaccharide Extracting from Cistanche on PC12 Nerve-Cell Damage Model Induced by D-galactose / 中国药学杂志

OBJECTIVE: To explore the protective effect of mullein glycoside polysaccharide of Cistanche deserticola Ma on PC12 nerve-cell model induced by D-galactose. METHODS: The cell survival rate was determined by MTT assays, which provided the basis for selecting mullein glycoside polysaccharide dose and estimated the dose and action time of D-galactose for inducing PC12 nerve cell damage model. After mullein glycoside polysaccharide incubation of PC12 cells, western blotting was used to detect the levels of CREB and p-CREB protein expression. ELISA Kit was used to detect the levels of cyclic adenosine monophosphate(cAMP), cAMP dependent protein kinase(PKA) and brain derived neurotrophic factor(BDNF). The content of MDA, activities of SOD and LDH were measured by their respective kits. RESULTS: (1)After the exposure of the PC12 cells to 16 g·L-1 D-galactose for 40 h, the cell survival rate was (46.67±6.59)%, which has a significant difference compared with the control group(P<0.05), indicating that successful cell aging model was established. (2)Compared with those in model group, mullein glycoside polysaccharide could significantly increase p-CREB expression in dose-dependent manner(r=0.989, P<0.01), content of PKA, cAMP, BDNF and SOD and decrease the levels of MDA and LDH(rMDA=0.875, P<0.05);(rLDH=0.834, P<0.05). However, blockers H-89 could significantly decrease p-CREB expression, PKA, cAMP, SOD and BDNF content(P<0.05), and increase the levels of MDA and LHD(P<0.05). CONCLUSION: The mullein glycoside polysaccharide of Cistanche deserticola Ma has obvious protective effect on PC12 nerve-cell damage model induced by D-galactose and its mechanism relates to the upregulation of cAMP/PKA/ CREB signaling pathways.

Effects of nerve cells and adhesion molecules on nerve conduit for peripheral nerve regeneration

BACKGROUND: For peripheral nerve regeneration, recent attentions have been paid to the nerve conduits made by tissue-engineering technique. Three major elements of tissue-engineering are cells, molecules, and scaffolds. METHODS: In this study, the attachments of nerve cells, including Schwann cells, on the nerve conduit and the effects of both growth factor and adhesion molecule on these attachments were investigated. RESULTS: The attachment of rapidly-proliferating cells, C6 cells and HS683 cells, on nerve conduit was better than that of slowly-proliferating cells, PC12 cells and Schwann cells, however, the treatment of nerve growth factor improved the attachment of slowly-proliferating cells. In addition, the attachment of Schwann cells on nerve conduit coated with fibronectin was as good as that of Schwann cells treated with glial cell line-derived neurotrophic factor (GDNF). CONCLUSIONS: Growth factor changes nerve cell morphology and affects cell cycle time. And nerve growth factor or fibronectin treatment is indispensable for Schwann cell to be used for implantation in artificial nerve conduits.

Effects of Erythropoietin on Nerve Function and Brainstem Auditory Evoked Potential in the Preterm Chil-dren with Brain Damage / 中国药房

OBJECTIVE:To investigate the effects and safety of erythropoietin on nerve function and brainstem auditory evoked potential in the preterm children with brain damage. METHODS:46 preterm children with brain damage were randomly di-vided into treatment group and control group,with 23 cases in each group. Control group received conventional symptomatic treat-ment as respiratory support,nutritional support,vitamin K supplement and ganglioside. Treatment group was additionally given rhE-PO for injection (CHO cell) 500 IU/kg hypodermically,3 times a week,on the basis of control group. Both group received 3-4 weeks of treatment continuously. MDI,PDI,the content of serum nerve injury factor(NSE,S-100β),latent period and peak inter-val of brainstem auditory evoked potential were compared between 2 groups before and after treatment,and the occurrence of ADR was observed in 2 groups. RESULTS:There was no statistical significance in MDI,PDI,the content of serum nerve injury mole-cule,latent period and peak interval of brainstem auditory evoked potential between 2 groups before treatment (P>0.05). After treatment,MDI and PDI of 2 groups increased significantly,while the content of serum nerve injury factor,latent period and peak interval of brainstem auditory evoked potential decreased significantly;the treatment group was better than the control group,with statistical significance (P<0.05). No obvious ADR was found in 2 groups. CONCLUSIONS:Erythropoietin can significantly im-prove intelligence development,protect the damaged nerve cells and auditory nerve pathways with good safety.

Research progress of methamphetamine inducing nerve cell′s autophagy / 中国药理学通报

Methamphetamine ( METH ) , a powerful stimulant of amphetamine type in the central nervous system ( CNS ) , is a new kind of synthetic drugs mainly in psychological dependence. Long-time abuse will lead to strong neurotoxicity and drug de-pendence. Recently it has become the abuse problem in public health. Autophagy is a process of degradation and utilization of the cellular components by the lysosome, which widely exists in eukaryotic cells. Many studies show that methamphetamine can iduce autophagy,but the underlying mechanism is not fully un-derstood yet . Therefore,the mechanisms and signaling pathways of autophagy by methamphetamine and the roles of autophagy in methamphetamine induce neurotoxicity are reviewed in this pa-per, so as to provide reference materials for further research of methamphetamine and autophagy.

Effect of resveratrol on sevoflurane-induced nerve cell injury / 临床麻醉学杂志

Objective To investigate the effect of resveratrol (RES)on sevoflurane-induced nerve cell injury and its mechanism.Methods Fetal hippocampal tissues were taken from SD pregnant rats and primary nerve cells were isolated and cultured,then the cells were randomly divided into four groups:group control (group C),normal primary nerve cells;group 3% sevoflurane (group S),cells treated with 3% sevoflurane gas;group 3% sevoflurane+RES (group SR),cells treated with RES for 6 h,and then treated with 3% sevoflurane gas;group RES (group R),cells treated with RES.Flow cytometry assay was used to detect the apoptosis of nerve cell;CCK-8 Kit was used to detect cell proliferation;Western blot was used to detect the expression level of Caspase-3,Bax,Bcl-2 and Bace-1;ELISA method was used to detect the protein level of amyloid precursor protein (APP)andβ-amyloid peptide (Aβ).Results Compared with the group C,cell apoptosis was increased (P <0.05),cell proliferation was decreased (P <0.05),the expression levels of Caspase-3 and Bax were up-regulated (P <0.05),the expression level of Bcl-2 was down-regulated (P <0.05), and the protein levels of Bace-1,APP and Aβwere significantly decreased by 3% sevoflurane treat-ment (P <0.05),which were all significantly reversed by RES treatment.Compared with group S, cell apoptosis was decreased (P <0.05),cell proliferation was increased (P <0.05),the expression levels of Caspase-3 and Bax were down-regulated (P <0.05),the expression level of Bcl-2 was up-regulated (P <0.05),and the protein levels of Bace-1,APP and Aβwere increased in group SR (P <0.05).Conclusion Resveratrol alleviated sevoflurane-induced nerve cell injury in vitro by reducing cell apoptosis and promoting cell proliferation,which may be related with the reduction of Aβexpression and the reduced Aβ-induced neurotoxicity.

Effects of astragaloside IV combined with active components of Panax notoginseng on apoptosis and endoplasmic reticulum stress in brain tissues after cerebral ischemia-reperfusion in mice / 中草药

Objective: To probe the effects and mechanisms of astragaloside IV combined with the active components from Panax notoginseng on apoptosis of nerve cells through endoplasmic reticulum stress (ERS) after cerebral ischemia-reperfusion (I/R) in mice. Methods: C57BL/6 mice were randomly divided into Sham, model, astragaloside IV (AST IV), ginsenoside Rg1 (Rg1), ginsenoside Rb1(Rb1), notoginsenoside R1 (R1), four active components combination, AST IV + Rg1, AST IV + Rb1, AST IV + R1 and Edaravone group, pretreated for 3 d. After 1 h of the last administration, the model of cerebral I/R injury was established by bilateral common carotid artery (CCA) ligation followed by reperfusion, then TUNEL method was used to detect the apoptosis in hippocampal CA1 and apoptosis rate was calculated; The expression of cysteine aspartic acid specific protease (Caspase-3), glucose regulated protein 78 (GRP78), Caspase-12 and phosphorylated C-Jun amino terminal enzyme (p-JNK1/2) proteins in brain tissues was tested by Western-blotting at 24 h after reperfusion. Results: After cerebral ischemia for 20 min followed by reperfusion 24 h, the apoptosis rate of nerve cell in hippocampal CA1 and the expression of Caspase-3 protein in brain tissues were increased. All drugs could decrease the apoptosis rate and inhibit Caspase-3 protein expression. Furthermore, the decreased effects of AST IV + Rg1 and AST IV + R1 on the apoptosis rate and Caspase-3 protein expression were better than those of the active components alone; In the four active components combination, the decrease of the apoptosis rate was stronger than that of the four active components alone and the inhibition of AST IV + Rb1 on Caspase-3 was greater than that of the four active components alone as well as AST IV + Rb1 and AST IV + R1. After the cerebral I/R, the expression of GRP78 and Caspase-12, p-JNK1/2 proteins were up-regulated. AST IV, Rg1, R1, and the combinations could further increase GRP78 protein expression in brain tissues, and the effect of the combinations was better than that of the active components alone; The effect of the four active components combination was better than that of AST IV + Rb1 and AST IV + R1. R1, the four active components combination, AST IV + Rg1, and AST IV + R1 could down-regulate Caspase-12 protein, and the effect of the four active components combination was more obvious than that of the four active components alone and AST IV + Rb1. The expression of p-JNK1/2 in AST IV, Rg1, the four active components combination, AST IV + Rg1, and AST IV + Rb1 was decreased, the decrease in the four active components combination was stronger than that in the four active components alone as well as AST IV + Rg1 and AST IV + R1. Conclusion: AST IV combined with the effective components from P. notoginseng has the potentiation on the inhibition of apoptosis, and the mechanism underlying might be associated with relieving ERS via different links. AST IV + Rb1 might affect JNK pathway and AST IV + R1 might act on the Caspase-12 pathway; Moreover, the four active components combination and AST IV + Rg1 could act on both Caspase-12 and JNK.

The progress of induced pluripotent stem cells in neural developmental diseases / 国际儿科学杂志

Induced pluripotent stem cell ( iPS cell ) , similar to embryonic stem cell, can be repro-grammed to the pluripotent state by ectopic expression of specific transcription factors. The iPS cells have pluri-potency and can be induced into neuron cells,which represent a promising cellular tool to study human neurode-velopmental disease,drug screening,diagnosis and personalized treatment. This article reviews the latest progress on iPS cell and its applications in neural developmental disease.

Chitosan Promoting the Growth of in vitro Cultured Retinal Nerve Cells of SD Baby Rats / 华中科技大学学报(医学版)

Objective To study the effect of chitosan on the growth of the in vitro cultured retinal nerve cells. Methods The retinal nerve cells of SD baby rats were cultured in vitro. The effects of chitosan at 0.065%,1.25%,2.5%,5%,10%,15% on the growth of the retinal nerve cells were measured by MTT method. The blank control group was created. Results 1.25%,2.5%,5%,and 10% chitosan could obviously promote the growth of retinal nerve cells,and 10% chitosan was the optimal concentration for the growth of nerve cells. Conclusion Chitosan can effectively promote the growth of retinal nerve cells,and it is necessary to undertake the further study of Chitosan.

Effects of different doses of topiramate on expression of NCAM and GAP- 43 mRNA in hippocampus of rats with epilepsy / 上海交通大学学报（医学版）

Objective To explore the effects of different doses of topiramate (TPM) on the expression of nerve cell adhesion molecule (NCAM) and growth-associated protein 43 (GAP- 43) mRNA in hippocampus of rats with epilepsy. MethodsForty-eight rats were randomly divided into normal control group, kainic acid (KA) group, 10 mg/kg TPM group, 40 mg/kg TPM group, 100 mg/kg TPM group and 400 mg/kg TPM group (n=8). The models of rats with epilepsy treated by different doses of TPM were established. The behavior of rats was observed, and the expression of NCAM and GAP- 43 mRNA in hippocampus of rats was determined by Real-time PCR. Results The expression of NCAM and GAP- 43 mRNA in KA group was significantly higher than that in normal control group (P<0.01), while there was no significant difference between 10 and 40 mg/kg TPM groups and KA group, that in 100 and 400 mg/kg TPM groups was significantly lower than that in KA group (P<0.01), and that in 400 mg/kg TPM group was significantly lower than that in 100 mg/kg TPM group (P<0.01). Conclusion KA can up-regulate the expression of NCAM and GAP- 43 mRNA in hippocampus of rats with epilepsy. Higher dose of TPM can inhibit the expression of NCAM and GAP- 43 mRNA, and the inhibitory effect is related with the dose of TPM.

Effects of the Velvet Antler Polypeptides on Spinal Nerve Cell Apoptosis Induced by ?-amyloid Peptide / 浙江中医药大学学报

[Objective] To study effects of the velvet antler polypeptides on spinal nerve cell apoptosis induced by ?-amyloid peptide. [Method]Spinal nerve cells were performed serial subcultivation,and entered into experiment during the exponential phase of growth.The viability of spinal nervecells 24h after induction by ?-amyloid peptide with different concentrations were detected by MTT assay,percentages of the cell apoptosis and expression of casepase-3 were detected after induction by 25?mol/L ?-amyloid peptide.[Result]It was revealed that 24 h after treatment with ?-amyloid peptide of different concentrations,the viability of spinal nerve cells was significantly decreased in a dose-dependent manner(P

Functions of MicroRNA in Nervous System Regulation / 生物化学与生物物理进展

Many investigations have demonstrated that microRNA (miRNA) is not only involved in the modulation of nerve cell growth and physiological activity, but also responsible for dysfunctions in synaptogenesis or synaptic plasticity, neurodegenerative diseases, tumorgenesis in the nervous system, as well as in cerebrovascular disorders. With the intensive researches in miRNA, it is possible gradually to explain the related pathogenic mechanisms of some major diseases in the nervous system.

Effect of He-Ne Laser Irradiation on Proliferation and Differentiation of Rat Embryo Midbrain Nerve Cell / 医学研究杂志

Objective To study the effect of He-Ne laser at lower power on proliferation and differentiation of embryo midbrain nerve cell.Methods The embryo midbrain nerve cell of rat embryo were randomly divided into one control group and three experimental groups.The cells in experimental groups were respectively irradiated at different time:3 min(A组),6 min(B组),10min(C组),each day.After ten days,we counted the concentration rate and determined the content of protein and the amount of superoxide dismutase(SOD)and malonyldialolehyde(MDA).Results The concentration rate of group A and of group B significantly increased than that of the control group(P

Effect of Low Power Laser Irradiation on the Proliferation and Differentiation of PC12 Nerve Cells

OBJECTIVE: We examined the effect of low power laser irradiation (LPLI) on the proliferation and differentiation of PC12 nerve cells. METHOD: After seeding 4x10(5) PC12 nerve cells each in the 24 well-culture dishes, we cultured them for 6 days with RPMI1640 media. LPLI (650 nm, 5 mW, 5 sec) was applied for 1 day, 2 days and 3 days (1, 2 and 3-day-LPLI groups) consecutively. For the degree of proliferation of PC12 nerve cells, we compared the total cell number at 6th day after LPLI by MTT cell proliferation assay. For the degree of differentiation, we compared the length of neurite out-growth and the expression of RT97 at 6th day after adding nerve growth factor on each group. RESULTS: The total cell numbers were increased significantly after LPLI, but those increments were not significant among 1, 2, and 3-day-LPLI groups. The numbers of the differentiated PC12 nerve cells and the expressions of RT97 were diminished serially according to the number of days of LPLI. CONCLUSION: We conclude that LPLI increased the proliferation and decreased the differentiation of PC12 nerve cells. We could suggest that single or short-term use of LPLI on the injured nerve should be helpful for enhancing the neural regeneration in vivo.

Changes of CGRP immunoreactivity in rat trigeminal ganglion neurons during tooth movement / 대한치과교정학회지

GRP was known as the modulator of pain transmission in central nervous system and local effector to peripheral tissue causing vasodilation, increased blood flow, modulation of immune system, stimulation of endothelial cell proliferation, and stimulation of bone formation. Numerous study, therefore, were done to elucidate involvement of CGRP to tooth movement. To investgate the response of CGRP immunoreactive nerve cells according to cell size in trigemeinal ganglion during tooth movement, immunohistochemical study was performed using rat. Experimental rats(9 weeks old, 210 gm) were divided as six groups(normal(n=6), 3 hours group(n=5), 12 hour group(n=4), 1 day group(n=5), 3 day group(n=5), 7 day group(n=5)), and were applied orthodontic force (approximately 30 gm) to upper right maxillary molar. After frozen sections of trigeminal ganglions were immunostained using rabbit antisera, the changes of CGRP immunoreactive cells in regard to cell size distribution(small cell(up to 20 microgramm), medium cell(20-35 microgramm), large cell(above 35 microgramm)) were observed. The results were as follows 1. The percentage of CGRP immunoreactive cells to all nerve cells in trigeminal ganglion was 33.0% in normal control group, was decreased to 24.5% in 1 day group, and was increased to 41.8% in 7 day group. 2. The percentage of small, medium, and large cells expressing CGRP immunoreactivity in normal trigeminal ganglion to all CGRP immunoreactive cells were 51.3%, 44.0%, 4.7%, respectively. 3. The percentage of small cells with CGRP immunoreactivity to all CGRP immunopositive cells was increased in 3 hour and 12 hour groups. 4. The percentage of medium cells with CGRP immunoreactivity was increased in 3 day and 7 day groups. 5. The percentage of large cells with CGRP immunoreactivity was increased in 7 day group. Conclusively, the small cells with CGRP immunoreactivity in trigeminal ganglion respond to orthodontic force during initial phase of tooth movement, and later the medium and large with CGRP immunoreactivity respond.