Animals ; Ciliary Neurotrophic Factor ; genetics ; metabolism ; Microwaves ; RNA, Messenger ; genetics ; Rabbits ; Retina ; metabolism ; radiation effects

OBJECTIVETo investigate the changes of cholinergic neurotrophic factors (CNTF) protein at different time points and the distribution of CNTF in rabbit retina after exposure to high power microwave (HPM), in order to determine the changes rule of CNTF protein.

METHODSThe rabbits were irradiated by HPM (peak power 90 W/cm(2)) for 15 min respectively, and then killed at 0, 3, 6, 12, 24 and 72 h after irradiation. The changes of CNTF protein were investigated by immunohistochemistry and semi-quantity analysis.

RESULTSCNTF protein was distributed in full retinal layers, special in the cell membrane and cytoplasm. HPM irradiation could immediately down-regulated CNTF protein expression at 0 h, up-regulated and arrived at peak level at 6 h (P<0.05 vs 0 h group), and then kept control level.

CONCLUSIONHPM may cause acute retinal injure and change the expression of CNTF protein in rabbit retina. These effects show the time-dependent feature. These results suggest that CNTF activation plays a central role in the retinal injures induced by HPM, and supplies a therapy method by using foreign-aid CNTF to remedy the retinal injure induced by HPM.

Animals ; Ciliary Neurotrophic Factor ; metabolism ; Female ; Male ; Microwaves ; adverse effects ; Rabbits ; Retina ; metabolism ; radiation effects

Ciliary neurotrophic factor (CNTF) is well known as a growth/survival factor of neuronal tissue. We investigated the expression of CNTF and its specific receptor alpha (CNTFRalpha) in a unilateral ureteral obstruction (UUO) model. Complete UUO was produced by left ureteral ligation in Sprague-Dawley rats. The animals were sacrificed on days 1, 3, 5, 7, 14, 21, and 28 after UUO. The kidneys were fixed, and processed for both immunohistochemistry and in situ hybridization. CNTF immunoreactivity in sham-operated kidneys was observed only in the descending thin limb (DTL) of the loop of Henle. In UUO kidneys, CNTF expression was induced in the S3 segment (S3s) of the proximal tubule from day 1, and progressively expanded into the entire S3s and a part of the convoluted proximal tubules, distal tubules (DT), and glomerular parietal epithelium up to day 7. Upregulated CNTF expression was maintained to day 28. From day 14, the inner medullary collecting duct showed weak CNTF immunoreactivity. The CNTFRalpha mRNA hybridization signal in sham-operated kidneys was weakly detected in the DTL, DT, medullary thick ascending limb, and in a few S3s cells. After UUO, CNTFRalpha mRNA expression increased progressively in both the renal cortex and the medulla up to day 7 and increased expression was maintained until day 28. The results suggest that the S3s may be the principal induction site for CNTF in response to renal injury, and that CNTF may play a role in chronic renal injury.
Animals ; Chimera ; Ciliary Neurotrophic Factor ; Ciliary Neurotrophic Factor Receptor alpha Subunit ; Epithelium ; Extremities ; Immunohistochemistry ; In Situ Hybridization ; Kidney ; Ligation ; Loop of Henle ; Neurons ; Rats, Sprague-Dawley ; RNA, Messenger ; Ureter ; Ureteral Obstruction

PURPOSE: Acute leukemia (AL) is classified as acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). This study aimed to investigate the effect of miR-146a on childhood AL and its underlying molecular mechanisms. MATERIALS AND METHODS: Bone marrow samples were obtained from 39 AL children and 10 non-cancer controls. The expressions of miR-146a and ciliary neurotrophic factor receptor (CNTFR) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) in ALL and AML pediatric patients, as well as ALL (Jurkat) and AML (HL-60) cells. Correlations between miR-146a and clinical indicators were explored. A targeting relationship between miR-146a and CNTFR was detected by dual luciferase reporter gene assay. Cell proliferation, apoptosis, migration, and invasion of Jurkat and HL-60 cells were measured by MTT assay, flow cytometry, and transwell assay, respectively. LIF expression was detected by qRT-PCR in Jurkat and HL-60 cells. The expression of p-JAK2, JAK2, p-STAT3, and STAT3 in HL-60 cells was measured by Western blot. RESULTS: miR-146a was increased in ALL and AML pediatric patients, while CNTFR was decreased. miR-146a expression was associated with immunophenotype, karyotype, fusion gene, and SIL-TAL1. CNTFR was a target gene of miR-146a. miR-146a could promote cell proliferation, migration, and invasion, as well as inhibit cell apoptosis in Jurkat and HL-60 cells by downregulating CNTFR. Meanwhile, miR-146a inhibited the expression of LIF and activated JAK2/STAT3 pathway by downregulating CNTFR. CONCLUSION: miR-146a could promote the proliferation, migration, and invasion and inhibit the apoptosis of AL Jurkat and HL-60 cells by downregulating CNTFR and activating the JAK2/STAT3 pathway.
Apoptosis ; Blotting, Western ; Bone Marrow ; Cell Proliferation ; Child ; Ciliary Neurotrophic Factor ; Flow Cytometry ; Genes, Reporter ; HL-60 Cells ; Humans ; Karyotype ; Leukemia ; Leukemia, Myeloid, Acute ; Luciferases ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Real-Time Polymerase Chain Reaction ; Receptor, Ciliary Neurotrophic Factor

Transient receptor potential vanilloid subtype 1 (TRPV1) on astrocytes prevents ongoing degeneration of nigrostriatal dopamine (DA) neurons in MPP⁺-lesioned rats via ciliary neurotrophic factor (CNTF). The present study determined whether such a beneficial effect of astrocytic TRPV1 could be achieved after completion of injury of DA neurons, rather than ongoing injury, which seems more relevant to therapeutics. To test this, the MPP⁺-lesioned rat model utilized here exhibited approximately 70~80% degeneration of nigrostriatal DA neurons that was completed at 2 weeks post medial forebrain bundle injection of MPP⁺. TRPV1 agonist, capsaicin (CAP), was intraperitoneally administered. CNTF receptor alpha neutralizing antibody (CNTFRαNAb) was nigral injected to evaluate the role of CNTF endogenously produced by astrocyte through TRPV1 activation on DA neurons. Delayed treatment of CAP produced a significant reduction in amphetamine-induced rotational asymmetry. Accompanying this behavioral recovery, CAP treatment increased CNTF levels and tyrosine hydroxylase (TH) activity in the substantia nigra pars compacta (SNpc), and levels of DA and its metabolites in the striatum compared to controls. Interestingly, behavioral recovery and increases in biochemical indices were not reflected in trophic changes of the DA system. Instead, behavioral recovery was temporal and dependent on the continuous presence of CAP treatment. The results suggest that delayed treatment of CAP increases nigral TH enzyme activity and striatal levels of DA and its metabolites by CNTF endogenously derived from CAP-activated astrocytes through TRPV1, leading to functional recovery. Consequently, these findings may be useful in the treatment of DA imbalances associated with Parkinson's disease.
Animals ; Antibodies, Neutralizing ; Astrocytes ; Capsaicin ; Ciliary Neurotrophic Factor ; Dopamine ; Dopaminergic Neurons ; Medial Forebrain Bundle ; Models, Animal ; Neurons ; Parkinson Disease ; Pars Compacta ; Rats ; Receptor, Ciliary Neurotrophic Factor ; Tyrosine 3-Monooxygenase

Ciliary neurotrophic factor (CNTF) is one of the important factors in neuronal survival. Mutation in CNTF gene was found first in Japanese. We analyzed the CNTF genotype of 187 healthy volunteer of Korean, and compared the frequency difference in CNTF gene mutation among Korean, Japanese, and other nations or race. The number of normal homozygote was 138 (73.8%), mutant homozygote 47 (25.1%), and mutant homozygote was 2 (1.1%). The mutated allele frequency of CNTF gene in Korean was 13.6%, which was not significantly different from that of other nations or race (10~20%).
Asian Continental Ancestry Group ; Ciliary Neurotrophic Factor* ; Continental Population Groups ; Gene Frequency ; Genotype ; Healthy Volunteers ; Homozygote ; Humans ; Neurons

Genetic factors play an important role in the development of schizophrenia and bipolar disorder, and recently the neural maldevelopment hypothesis is suggested by neuropathological and neuroimaging studies. Neurotrophic factors, including ciliary neurotrophic factor (CNTF), play a central role in the regulation of neural development. This study was designed to investigate the association between the null mutation of CNTF gene and schizophrenia and bipolar disorder in a Korean population. The CNTF gene were typed with polymerase chain reaction in 112 patients with schizophrenia, 81 with bipolar disorders and in 125 healthy controls. The distributions of the CNTF genotype in schizophrenic patients with N/N, N/M, M/M were 80 (71.4%), 32 (28.6%), 0 (0%), in bipolar disorders were 58 (71.6%), 23 (28.4%), 0 (0%) and in the controls were 94 (75.2%), 30 (24.0%), 1 (0.8%). The allele frequencies of the CNTF gene in schizophrenic patients with N and M were 192 (85.7%), 32 (14.3%), in bipolar disorders were 139 (85.8%), 23 (14.2%), and in the control were 218 (87.2%), 32 (12.8%). There were no differences in the genotype distributions and the allele frequencies of CNTF gene null mutation among the 3 groups. These results suggest CNTF gene null mutation is not causally related to the development of schizophrenia and bipolar disorder in Korea.
Bipolar Disorder* ; Ciliary Neurotrophic Factor* ; Gene Frequency ; Genotype ; Humans ; Korea ; Nerve Growth Factors ; Neuroimaging ; Polymerase Chain Reaction ; Schizophrenia*

Neural stem/progenitor cells (NSCs) can spontaneously differentiate into neurons and glial cells in the absence of mitogen fibroblast growth factor-2 (FGF-2) or epidermal growth factor (EGF) in medium and the spontaneous differentiation of NSCs is mediated partially by endogenous ciliary neurotrophic factor (CNTF). This study examined the relationship of FGF-2 and CNTF in the spontaneous differentiation of adult hippocampal progenitor cells (AHPs). AHPs were cultured in the medium containing different concentration of FGF-2 (1-100 ng/mL). Western blotting and immunofluorescence staining were applied to detect the expression of the astrocytic marker GFAP, the neuronal marker Tuj1, the oligodendrocytic marker CNPase and, Nestin, the marker of AHPs. The expression of endogenous CNTF in AHPs at early (passage 4) and late stage (passage 22) was also measured by Western blotting. The results showed that FGF-2 increased the expression of Nestin, dramatically inhibited the expression of GFAP and Tuj1 and slightly suppressed the expression of CNPase. FGF-2 down-regulated the expression of endogenous CNTF in AHPs at both early (passage 4) and late stage (passage 22). These results suggested that FGF-2 could inhibit the spontaneous differentiation of cultured AHPs by negatively regulating the expression of endogenous CNTF in AHPs.
Animals ; Cell Differentiation ; physiology ; Ciliary Neurotrophic Factor ; metabolism ; Fibroblast Growth Factor 2 ; metabolism ; Hippocampus ; metabolism ; physiology ; Male ; Rats ; Rats, Wistar ; Stem Cells ; metabolism ; physiology

OBJECTIVETo investigate the effects of nerve growth factor (NGF) and ciliary neurotrophic factor (CNTF) to promoting the sensitive and motor fibres regeneration.

METHODSThirty two Sprague-Dawley rats with 10 mm gap of sciatic nerve were operated and bridged with the new double channel nerve conduit in rhomboid shape. They were randomly divided into two groups, with each in twelve animals. In the first group, 200 micro1 of chitin for medical use was injected into the conduit, and in the second group the two branches of the conduit contained 100 microl of the chitin and 5 microl NGF or CNTF. At twelve and sixteen weeks after the operation, we evaluated the sensitive and motor fibres of regenerative nerve with Holmes, Acetylcholinesterase and Carbonic anhydrase staining.

RESULTSAfter the twelve and sixteen weeks of the operation, there were not significant differences of the regenerative nerve fibres between two channels in the first groups. But in the second group, the number of the motor fibres of the regenerative nerve of CNTF branch channel was much more and distributed better than the others, while the number and density of sensitive fibres was inferior to NGF. The latency of compound muscle active potential and cortical somatosensory evoked potential of the nerve in the CNTF branch was shorter than the one in the NGF branch, but its amplitude was higher.

CONCLUSIONSThe CNTF could significantly promote the regeneration of motor fibres and the NGF could promote better for the regeneration of sensitive fibres.

Animals ; Ciliary Neurotrophic Factor ; pharmacology ; Female ; Male ; Motor Neurons ; Nerve Growth Factor ; pharmacology ; Nerve Regeneration ; drug effects ; Neurons, Afferent ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo review the updated research on neuroprotection in glaucoma, and summarize the potential agents investigated so far.

DATA SOURCESThe data in this review were collected from PubMed and Google Scholar databases published in English up to September 2012, with keywords including glaucoma, neuroprotection, and retinal ganglion cells, both alone and in combination. Publications from the past ten years were selected, but important older articles were not excluded.

STUDY SELECTIONArticles about neuroprotection in glaucoma were selected and reviewed, and those that are cited in articles identified by this search strategy and judged relevant to this review were also included.

RESULTSAlthough lowering the intraocular pressure is the only therapy approved as being effective in the treatment of glaucoma, increasing numbers of studies have discovered various mechanisms of retinal ganglion cells death in the glaucoma and relevant neuroprotective strategies. These strategies target neurotrophic factor deprivation, excitotoxic damage, oxidative stress, mitochondrial dysfunction, inflammation, activation of intrinsic and extrinsic apoptotic signals, ischemia, and protein misfolding. Exploring the mechanism of axonal transport failure, synaptic dysfunction, the glial system in glaucoma, and stem cell used in glaucoma constitute promising research areas of the future.

CONCLUSIONSNeuroprotective strategies continue to be refined, and future deep investment in researching the pathogenesis of glaucoma may provide novel and practical neuroprotection tactics. Establishing a system to assess the effects of neuroprotection treatments may further facilitate this research.

Apoptosis ; Axonal Transport ; Brain-Derived Neurotrophic Factor ; physiology ; Ciliary Neurotrophic Factor ; physiology ; Glaucoma ; etiology ; therapy ; Humans ; Mitochondria ; physiology ; Neuroprotective Agents ; therapeutic use ; Oxidative Stress ; Protein Folding ; Receptors, N-Methyl-D-Aspartate ; physiology ; Retinal Ganglion Cells ; physiology