OBJECTIVETo investigate the role of p75 neurotrophin receptor (p75NTR) in the regeneration of facial nerve crush injury.

METHODSIn p75NTR knockout mice and wild type mice, the regenerating fibres in the facial nerve were also labelled by an anterograde tracer cholera toxin B (CTB). The next day after injury of facial nerve, CTB was injected into the trunk of the nerve in the proximal side of the crush, and then anterograde tracing and immunohistochemistry were used to examine the regeneration of axons after facial nerve crush injury. In p75NTR knockout mice and wild type mice, the facial nerves on one side were crushed and regenerating neurons in the facial nerve nucleus were labelled by Fast Blue. The facial nerve trunk was cut in the bifurcated region in the 4th day after injury and the stump was inserted into a small polymer tube containing Fast Blue. Retrograde tracing and labling motoneuron counting were used to examine the survival of motoneurons in the facial nerve nucleus after facial nerve crush injury.

RESULTSThe results showed that the axonal growth of injured axons in the facial nerve of p75NTR knockout mice was significantly retarded. The number of regenerated neurons in the facial nerve nucleus in p75NTR knockout mice was significantly reduced (P < 0.05). Immunohistochemical staining of regenerating axons also showed the reduction in nerve regeneration in p75NTR knockout mice (P < 0.01).

CONCLUSIONp75NTR plays an important role in the regeneration of injured peripheral nerves after injury.

Animals ; Axons ; Facial Nerve ; Mice ; Motor Neurons ; Nerve Regeneration ; Neurons ; Receptor, Nerve Growth Factor ; Receptors, Nerve Growth Factor

No abstract available.
Animals ; Rats* ; Receptor, Nerve Growth Factor* ; Suprachiasmatic Nucleus*

Humans ; Nerve Growth Factor ; physiology ; Pain ; physiopathology ; Pulpitis ; physiopathology ; Receptor, Nerve Growth Factor ; physiology ; Receptor, trkA ; physiology

Red Liriope platyphylla (RLP) has been manufactured from Liriope platyphylla (L. platyphylla, LP) roots using steaming process and investigated as a curative agent for treatment of diabetes, obesity and neurodegenerative disorders. To examine the precautionary effects of aqueous extract RLP (AEtRLP) on the preclinical stages of Alzheimer's Disease (AD), alterations of the key factors influencing AD were investigated in Tg2576 mice after AEtRLP7 treatment for 4 months. Abeta-42 peptides level was significantly decreased in the brain of AEtRLP7-treated Tg2576 mice compared to vehicle-treated Tg2576 mice, although significant differences on improving behavioral defects were not observed in the same group. The concentration of nerve growth factor (NGF) in serum was also higher in AEtRLP7-treated Tg2576 mice than vehicle-treated Tg2576 mice. However, the phosphorylation of TrkA and Erk among the downstream effectors of the high affinity NGF receptor was significantly lower in AEtRLP7-treated Tg2576 mice. A similar pattern was observed in the expression level of downstream effectors within low affinity NGF receptor. Overall, these results suggest that AEtRLP7 can contribute to preventing the production and deposition of Abeta-42 peptides during the early progression stage of AD in the brain of Tg2576 mice through increased NGF secretion.
Alzheimer Disease* ; Animals ; Brain ; Mice* ; Nerve Growth Factor* ; Neurodegenerative Diseases ; Obesity ; Peptides ; Phosphorylation ; Receptor, Nerve Growth Factor ; Steam

OBJECTIVETo assess the effects of both TrkA and p75(NTR) on nerve growth factor (NGF)-induced differentiation of neuroblastoma cells.

METHODSRetroviral vectors were constructed to express the high affinity NGF receptor (TrkA) and low affinity NGF receptor (p75(NTR)). Neuroblastoma cell line IMR-32 was transfected by the vectors expressing either TrkA or p75(NTR) or both by using lipofectmine trade mark reagent separately or cotransfected at the same time. Southern blot, Northern blot, RT-PCR and flow cytometry were used to determine the success of the transfection. MTT technique was to monitor the cell proliferation. Colony formation in soft agar and tumor forming assay in nude mice were used to test the biological characteristics of the tumor cells. Terminal-deoxynucleotidytransferase-mediated dUTP-biotin nick end labeling (TUNEL) assay was used to test the apoptosis of the tumor cells.

RESULTSStable transformant cell lines expressing TrkA, p75(NTR) or both genes were established. Studies on these transformant cell lines have shown different NGF responses. The p75(NTR) transfection only resulted in the mild differentiation response, and transfection of TrkA gene caused remarkable neurite extension, up-regulation of neurofilament and decreased expression of N-myc oncogene after NGF treatment. The cotransfection of the two genes into this cell line resulted in the more rapid and more apparent morphological changes than single TrkA transfected cells after NGF treatment. The cotransfected cells underwent apoptosis after withdrawal of NGF.

CONCLUSIONSThe results indicate that coexpression of both low- and high-affinity NGF receptors are not only more efficient in restoration of NGF-induced differentiation pathway, but also be able to activate the pro-apoptotic activity of low-affinity NGF receptor and make the tumor cells become NGF-dependent and irreversibly differentiated.

Animals ; Apoptosis ; Cell Differentiation ; Genes, myc ; Humans ; Mice ; Mice, Nude ; Nerve Growth Factor ; pharmacology ; Neuroblastoma ; pathology ; Receptor, Nerve Growth Factor ; Receptor, trkA ; physiology ; Receptors, Nerve Growth Factor ; physiology ; Transfection ; Tumor Cells, Cultured

The extracellular domain (p75ECD) of p75 neurotrophin receptor (p75NTR) antagonizes Aβ neurotoxicity and promotes Aβ clearance in Alzheimer's disease (AD). The impaired shedding of p75ECD is a key pathological process in AD, but its regulatory mechanism is largely unknown. This study was designed to investigate the presence and alterations of naturally-occurring autoantibodies against p75ECD (p75ECD-NAbs) in AD patients and their effects on AD pathology. We found that the cerebrospinal fluid (CSF) level of p75ECD-NAbs was increased in AD, and negatively associated with the CSF levels of p75ECD. Transgenic AD mice actively immunized with p75ECD showed a lower level of p75ECD and more severe AD pathology in the brain, as well as worse cognitive functions than the control groups, which were immunized with Re-p75ECD (the reverse sequence of p75ECD) and phosphate-buffered saline, respectively. These findings demonstrate the impact of p75ECD-NAbs on p75NTR/p75ECD imbalance, providing a novel insight into the role of autoimmunity and p75NTR in AD.
Mice ; Animals ; Alzheimer Disease/pathology* ; Receptor, Nerve Growth Factor ; Amyloid beta-Peptides ; Autoantibodies ; Mice, Transgenic

Immunohistochemical changes of epidermal growth factor receptor (EGFR) and nerve growth factor receptor (NGFR) were investigated in the rat mandibular molar and incisors after submandibular sialadenectomy. In the sham operated rat, any EGFR immunoreactivity was not observed in the teeth but NGFR immunoreactivities were observed exclusively in the periodontal ligament and ameloblasts of incisor. In the sialadenectomized rat, EGFR immunoreac-tivities were observed in the odontoblasts of the mandibular first molar, periodontal ligament cells, ameloblasts of incisor and some cells of bone marrow. NGFR immunoreactivities were more intense and widely distributed in alveolar bone, periodontal ligaments and odontoblasts of the sialadenectomized rat than in the sham operated rat. Both of EGFR and NGFR immunoreactivities gradually increased in their intensities in a time-dependent manner after submandibular sialadenectomy. The results show that expression of EGFR and NGFR in the mandibular molar and incisor is enhanced by submandibular sialadenectomy. Therefore, it is suggested that EGF and NGF derived from submandibular gland may affect to the mandibular molar and incisors by direct and/or indirect mechanism.
Ameloblasts ; Animals ; Bone Marrow ; Epidermal Growth Factor* ; Immunohistochemistry ; Incisor* ; Molar* ; Nerve Growth Factor ; Odontoblasts ; Periodontal Ligament ; Rats* ; Receptor, Epidermal Growth Factor* ; Submandibular Gland ; Tooth

The immunohistochemical localization of epidermal growth factor receptor (EGFR) and nerve growth factor receptor (NGFR) in the submandibular gland of rats was investigated after chronic administration of isoproterenol (IPR) or phenylephrine (PEP). The weight of submandibular gland relative to body weight increased sharply by IPR administration for 14 days and reached twice of that in control, while no significant differences were observed after PEP administration. In PTAH staining, the intensity of duct compartments in rats exposed to IPR and PEP were paler than that of controls. But small secretory granules were observed in the GCT cells of IPR administrated groups. Acini showed characteristic features of hypertrophy, decreased in number of nuclei per unit area, after IPR administration, but not after PEP. EGFR immunoreactivities were distributed mainly in the duct compartments including GCT cells, intercalated duct cells and secretory duct cells. EGFR immunoactivities were more intense after both of PEP and IPR administration than those in controls. However, EGFR immunoactivities gradually decreased after IPR administration. NGFR immunoreactivities were distributed mainly in connective tissue cells surrounding ducts, but not in duct cells. Their intensities increased in the rat with PEP administration but decreased by IPR administration. These results demonstrated that EGFR or NGFR is localized mainly in the duct cells or the cells surrounding ducts, respectively, and that both population of EGFR and NGFR immunoreactive cells are altered by PEP and IPR. The results suggest that EGF and NGF may have some physiological roles by binding with their specific receptors in the submandibular gland as well as oral cavity.
Animals ; Body Weight ; Connective Tissue Cells ; Epidermal Growth Factor* ; Hypertrophy ; Immunohistochemistry ; Isoproterenol ; Mouth ; Nerve Growth Factor ; Phenylephrine ; Rats* ; Receptor, Epidermal Growth Factor* ; Secretory Vesicles ; Submandibular Gland*

Liriope platyphylla (LP) has long been regarded as a curative herb for the treatment of diabetes, asthma, and neurodegenerative disorders. To examine the therapeutic effects of Red LP (RLP) manufactured by steaming process on neurodegenerative disorders, significant alteration of the key factors influencing Alzheimer's Disease (AD) was detected in NSE/hAPPsw transgenic (Tg) mice after RLP treatment. The concentration of nerve growth factor (NGF) in serum increased in RLP-treated NSE/hAPPsw Tg mice compared with vehicle-treated Tg mice. However, downstream effectors of the NGF receptor signaling pathway, including TrkA and p75NTR proteins, were suppressed in RLP-treated NSE/hAPPsw Tg mice. Especially, Tg mice showed decreased levels of TrkA, p75NTR, and RhoA expression. Production of Abeta-42 peptides was lower in RLP-treated NSE/hAPPsw Tg mice than in vehicle-treated Tg mice. Further, analysis of gamma-secretase components showed that Abeta-42 peptide expression was downregulated. Of the four components, the expression of APH-1 and Nicastrin (NCT) decreased in RLP-treated NSE/hAPPsw Tg mice, whereas expression of PS-2 and Pen-2 was maintained or increased within the same group. Overall, these results suggest that RLP can help relieve neurodegenerative diseases, especially AD, through upregulation of NGF secretion ability, activation of NGF signaling pathway, downregulation of Abeta-42 peptide deposition, and alteration of gamma-secretase components.
Alzheimer Disease ; Amyloid Precursor Protein Secretases ; Animals ; Asthma ; Down-Regulation ; Mice ; Mice, Transgenic ; Nerve Growth Factor ; Neurodegenerative Diseases ; Peptides ; Proteins ; Receptor, Nerve Growth Factor ; Steam ; Up-Regulation

In order to investigate the effects of a fermented soybean product (Chungkookjang, CKJ) on nerve growth factor (NGF) metabolism, NGF secretion ability and its related signaling pathway were analyzed in B35 neuronal cells and the Tg2576 mouse model of Alzheimer's disease (AD). In B35 cells, the concentration of NGF significantly increased upon treatment with Taegwang (TG)-CKJ and Shinhwa (SH)-CKJ extracts compared with vehicle. Further, a significant increase in PC12 cell length as well as the phsophorylation levels of TrkA and Akt, which are members of a high affinity NGF receptor signaling pathway, were observed after treatment with TG-CKJ and SH-CKJ conditional medium (CM). On the other hand, there was no difference in activation of the NGF receptor p75NTR signaling pathway between vehicle and all CKJ treated groups. In Tg2576 mice showing early stage of AD, the concentrations of NGF in the serum and brain were reduced compared with those in Non-Tg mice. Treatment of Tg2576 mice with SH-CKJ, which contains high concentrations of total flavonoids and phenolic compounds, for 8 weeks dramatically recovered the NGF level to that of Non-Tg mice. Furthermore, the low phosphorylation levels of TrkA and Erk in the NGF receptor TrkA signaling pathway were rapidly recovered to those of Non-Tg mice after SH-CKJ treatment in vehicle treated Tg2576 mice, whereas the phosphorylation level of Akt was maintained at a constant level. These results suggest that CKJ may stimulate NGF secretion ability as well as the NGF receptor TrkA signaling pathway in PC12 cells and Tg2576 mice.
Alzheimer Disease ; Animals ; Brain ; Flavonoids ; Hand ; Isoflavones ; Mice ; Nerve Growth Factor ; Neurons ; PC12 Cells ; Phenol ; Phosphorylation ; Receptor, Nerve Growth Factor ; Soybean Proteins ; Soybeans