NT-3 Levels Research Articles

Progesterone counteracts estrogen-induced increases in neurotrophins in the aged female rat brain

Neurotrophin alterations have been associated with normal aging and age-related neurodegenerative disease, as well as cognitive status. Estrogen influences expression of mRNA and protein of neurotrophins and their receptors, and affects cognitive performance in young ovariectomized (Ovx) rats. The current investigation evaluated whether estrogen or estrogen plus progesterone affects neurotrophin protein levels in cognitive brain regions in the aged Ovx rat. While estrogen treatment increased BDNF, NGF, and NT3 levels in entorhinal cortex, progesterone abated the effects of estrogen resulting in neurotrophin levels comparable to aged Ovx rats not given hormone. Our findings suggest that the aged female brain is responsive to estrogen in cognitive brain regions, and that progesterone can reverse these estrogen effects.

Passive smoking elevates neurotrophin levels in tears

The effect of passive smoking on levels of neurotrophin in tears was studied in normal subjects or patients with atopic keratoconjunctivitis (AKC). Basal levels of neurotrophins, nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and NT-4, in tears were significantly higher in AKC patients than those in normal subjects. Passive smoking had no effect on levels of neurotrophin in tears of normal subjects, while it elevated levels of NGF, BDNF, NT-3 and NT-4 in tears of AKC patients. These results indicate that passive smoking elevates levels of neurotrophin in tears, which in turn may aggravate AKC.

Alterations in IGF-I, BDNF and NT-3 levels following experimental brain trauma and the effect of IGF-I administration

The effects of a unilateral, penetrating brain trauma on IGF-I, BDNF and NT-3 were studied immunocytochemicaly in the rat. BDNF and NT-3 were decreased in the peritraumatic area, but increased in the adjacent region, 4 and 12 h post-injury. One week following the trauma, BDNF remained low in the peritraumatic area, but was restored to normal levels in the adjacent, while no effect of injury on NT-3 levels was detected in either area. Injury resulted in an increase in IGF-I levels in the peritraumatic area, which was most pronounced 1 week following the trauma, indicating that IGF-I could participate in endogenous repair processes. We thus administered IGF-I immediately following the trauma and investigated its effects on injury-induced changes in neurotrophin levels. Administration of IGF-I partially reversed the injury-induced decrease in BDNF and NT-3 in the peritraumatic area observed 4 and 12 h post-injury, while at the same time-points, it completely cancelled the effects of injury in the adjacent region. One week after the trauma, BDNF levels were dramatically increased in both the peritraumatic and adjacent area, reaching levels even higher than those of the sham-operated animals, following IGF-I administration. Our results showing that IGF-I not only counteracts injury-induced changes in neurotrophins, but can also further increase their levels, indicate that this growth factor could mediate repair and/or protective processes, following brain trauma.

Changes in retinal expression of neurotrophins and neurotrophin receptors induced by ocular hypertension.

Open angle glaucoma is defined as a progressive and time-dependent death of retinal ganglion cells concomitant with high intraocular pressure, leading to loss of visual field. Because neurotrophins are a family of growth factors that support neuronal survival, we hypothesized that quantitative and qualitative changes in neurotrophins or their receptors may take place early in ocular hypertension, preceding extensive cell death and clinical features of glaucoma. We present molecular, biochemical, and phenotypic evidence that significant neurotrophic changes occur in retina, which correlate temporally with retinal ganglion cell death. After 7 days of ocular hypertension there is a transient up-regulation of retinal NGF, while its receptor TrkA is up-regulated in a sustained fashion in retinal neurons. After 28 days of ocular hypertension there is sustained up-regulation of retinal BDNF, but its receptor TrkB remains unchanged. Throughout, NT-3 levels remain unchanged but there is an early and sustained increase of its receptor TrkC in Müller cells but not in retinal ganglion cells. These newly synthesized glial TrkC receptors are truncated, kinase-dead isoforms. Expression of retinal p75 also increases late at day 28. Asymmetric up-regulation of neurotrophins and neurotrophin receptors may preclude efficient neurotrophic rescue of RGCs from apoptosis. A possible rationale for therapeutic intervention with Trk receptor agonists and p75 receptor antagonists is proposed.

Kissing reduces allergic skin wheal responses and plasma neurotrophin levels

The effect of kissing on allergen-induced skin wheal responses and plasma neurotrophin levels were studied in 30 normal subjects, 30 patients with allergic rhinitis (AR), and 30 patients with atopic dermatitis (AD). All of the patients with AR or AD are allergic to house dust mite (HDM) and Japanese cedar pollen (JCP). They are all Japanese and they do not kiss habitually. The subject kissed freely during 30 min with their lover or spouse alone in a room with closed doors while listening to soft music. Before and after kissing, skin prick tests were performed using commercial HDM allergen, JCP allergen, as well as histamine and control solution, and wheal responses were measured. Simultaneously, plasma levels of neurotrophin, including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and -4 (NT-4) were measured. Kissing significantly reduced wheal responses induced by HDM and JCP, but not by histamine, and decreased plasma levels of NGF, BDNF, NT-3, and NT-4 in patients with AR or AD, while it failed to do so in normal subjects. These finding indicate that kissing have some implication in the study of neuroimmunology in allergic patients.

β-amyloid modulates tyrosine kinase B receptor expression in SHSY5Y neuroblastoma cells: influence of the antioxidant melatonin

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease in humans and is characterized by neuronal loss, neurofibrillary tangles and β-amyloid deposition. The interaction between neurotrophins and their tyrosine kinase (trk) receptors is important for cellular differentiation and survival. Interestingly, marked reductions in neurotrophins and receptors have been reported in AD. The cause of the decrease in these molecules remains unclear. However, the role of β-amyloid (Aβ) appears central in understanding the mechanisms controlling neurotrophin/trk expression. In this study we exposed SHSY5Y neuroblastoma cells to Aβ or hydrogen peroxide and measured the expression of trk B/truncated trk B, and brain-derived neurotrophic factor (BDNF)/NT4 at the protein and molecular level. We show that Aβ or hydrogen peroxide (H 2O 2) induces oxidative stress and cell cytotoxicity. The exposure of cells to Aβ results in an increased trk B expression with a concurrent reduction in truncated trk B levels. H 2O 2 exposure decreased both trk B and truncated trk B levels at the cell surface. At the molecular level trk B RNA increased in the presence of Aβ and was unaffected by H 2O 2. Similarly, BDNF and NT4 levels increased in the presence of Aβ. Pre-treatment of cells with the anti-oxidant melatonin returns trk receptor expression, mRNA and BDNF/NT4 secretion to normal levels. These results are significant as they can help in the planning and implementation of AD treatment strategies involving neurotrophins.

Increased expression of neurotrophins and their receptors in the mechanically compressed spinal cord of the spinal hyperostotic mouse (twy/twy)

The purpose of the present study was to identify any compensatory changes at the site of chronic compression of the spinal cord and neighboring segments. For this purpose, serial immunohistochemical and immunoblot analyses were performed for the expression levels of endogenous brain-derived neurotrophic factor (BDNF), neurotrophin (NT)-3, and their receptors, trkB and trkC in 24 tip-toe walking Yoshimura mice (twy/twy) aged 12-24 weeks. The twy mouse exhibits spontaneous calcified deposits posteriorly at the C1-C2 level, compressing the spinal cord. Immunoreactivities for BDNF, NT-3, trkB and trkC were preferentially localized in the gray matter, particularly in the anterior horn cells. In 24-week-old twy mice with severe compression, expression levels of these neurotrophins at the site of maximal compression were significantly lower than at the less- or non-compressed sites. In contrast, the expression levels of BDNF, NT-3, trkB and trkC were significantly higher at the rostral and caudal sites immediately adjacent to the maximal compression site. No such changes were noted in 12-week-old twy mice or in control Institute of Cancer Research mice. Our results suggest that overexpression of BDNF, NT-3, trkB and trkC in motoneuron areas neighboring the site of mechanical compression may represent compensatory changes in response to the compromised neuronal function at the level of compression, and that these proteins possibly contribute to neuronal survival and plasticity.

Elevated Levels of Neurotrophins in Human Biceps Brachii Tissue of Amyotrophic Lateral Sclerosis

Previous studies suggest that neurotrophins support regeneration and survival of injured motoneurons. Based on these findings, brain-derived neurotrophic factor (BDNF) has been clinically investigated for its therapeutic potential in amyotrophic lateral sclerosis (ALS), a rapidly progressing and fatal motoneuronal disease. We questioned whether imbalances of neurotrophic levels are indeed involved in the pathology of ALS. Therefore the expression of nerve growth factor (NGF), BDNF, neurotrophin-3 (NT-3), and neurotrophin-4/5 (NT-4/5) was investigated in postmortem muscle tissue of the biceps from 15 patients with neuropathologically confirmed sporadic ALS and 15 age-matched controls. Using mRNA analysis techniques and quantitative protein measurements, we have demonstrated that both mRNA and protein levels of all four neurotrophins are increased in muscle tissue of ALS patients. The production levels displayed a disease duration dependency and different expression patterns emerged for the four neurotrophins. Whereas the early phase of the disease was characterized by a strong upregulation of BDNF, levels of NGF, NT-3, and NT-4/5 gradually increased in the course of the disorder, peaking at later stages. We conclude that decreased neurotrophic support from muscle tissue is most likely not the cause of motoneuron degeneration in ALS. On the contrary, our results suggest that degenerating motoneurons in ALS are exposed to elevated levels of muscle-derived neurotrophins.

Differential expression of neurotrophic factors and inflammatory cytokines by myelin basic protein-specific and other recruited T cells infiltrating the central nervous system during experimental autoimmune encephalomyelitis.

Recent evidence suggests that autoimmune reactions in the central nervous system (CNS) not only have detrimental consequences but can also be neuroprotective, and that this effect is mediated by the expression of neuronal growth factors by infiltrating leucocytes. Here we dissect these two phenomena in guinea pig myelin basic protein peptide (gpMBP 63-88)-induced experimental autoimmune encephalomyelitis (EAE) in the Lewis rat. Real-time TaqMan polymerase chain reaction (PCR) was used to measure mRNA for the nerve growth factors, brain-derived neurotrophic factor (BDNF) and neurotrophin (NT)-3. As reference, the well-known proinflammatory mediator molecules interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha were quantified. In whole lumbar cord tissue, both the nerve growth factors and the proinflammatory cytokines, IFN-gamma and TNF-alpha, displayed similar expression patterns, peaking at the height of the disease. Among the infiltrating inflammatory cells isolated and sorted from the CNS, alphabeta+/T-cell receptor (TCR)BV8S2+, but not alphabeta+/TCRBV8S2-, recognized the encephalitogenic MBP peptide. Interestingly, these two populations displayed contrasting expression patterns of nerve growth factors and proinflammatory cytokines with higher inflammatory cytokine mRNA levels in alphabeta+/TCRBV8S2+ cells at all time intervals, whereas the levels of BDNF and NT3 were higher in alphabeta+/TCRBV8S2- cells. We conclude that a potentially important neuroprotective facet of CNS inflammation dominantly prevails within other non-MBP peptide-specific lymphoid cells and that there are independent regulatory mechanisms for neurotrophin and inflammatory cytokine expression during EAE.

Brain-derived neurotrophic factor and neurotrophin 3 in schizophrenic psychoses

Disturbed neural development has been postulated as a crucial factor in the pathophysiology of schizophrenic psychoses. The neurobiochemical basis for such changes of cytoarchitecture and changed neural plasticity could involve an alteration in the regulation of neurotrophic factors. In order to test this hypothesis, BDNF and NT-3 levels in post-mortem brain tissue from schizophrenic patients were determined by ELISA. There was a significant increase in BDNF concentrations in cortical areas and a significant decrease of this neurotrophin in hippocampus of patients when compared with controls. NT-3 concentrations of frontal and parietal cortical areas were significantly lower in patients than in controls. These findings lend further evidence to the neurotrophin hypothesis of schizophrenic psychoses which proposes that alterations in expression of neurotrophic factors could be responsible for neural maldevelopment and disturbed neural plasticity, thus being an important event in the etiopathogenesis of schizophrenic psychoses.

Partial prevention of cisplatin-induced neuropathy by electroporation-mediated nonviral gene transfer.

Cisplatin-induced sensory peripheral neuropathy is the dose-limiting factor for cisplatin chemotherapy. We describe the preventive effect of NT-3 delivery, using direct gene transfer into muscle by in vivo electroporation in a mouse model of cisplatin-induced neuropathy. Cisplatin-induced neuropathy was produced by weekly injections of cisplatin (five injections). Two doses of plasmid DNA encoding murine NT-3 (pCMVNT-3) were tested (5 and 50 microg/animal/injection). Cisplatin-treated mice were given two intramuscular injections. The first injection of pCMVNT-3 was given 2 days before the first injection of cisplatin and the second injection 2 weeks later. Six weeks after the start of the experiment, measurement of NT-3 levels (ELISA) demonstrated significant levels both in muscle and plasma. We observed a smaller cisplatin-related increase in the latency of the sensory nerve action potential of the caudal nerve in pCMVNT-3-treated mice than in controls (p < 0.0001). Mean sensory distal latencies were not different between the 5- and 50- microg/animal/injection groups. Treatment with gene therapy induced only a slight muscle toxicity and no general side effects. Therefore, neurotrophic factor delivery by direct gene transfer into muscle by electroporation is of potential benefit in the prevention of cisplatin-induced neuropathy and of peripheral neuropathies in general.

Region-specific neurotrophin imbalances in Alzheimer disease: decreased levels of brain-derived neurotrophic factor and increased levels of nerve growth factor in hippocampus and cortical areas.

Nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3), and neurotrophin 4/5 (NT-4/5) are members of the neurotrophin gene family that support the survival of specific neuronal populations, including those that are affected by neurodegeneration in Alzheimer disease (AD). To determine whether neurotrophin protein levels are altered in the AD-affected brain compared with control brains. We quantitated protein levels of NGF, BDNF, NT-3, and NT-4/5, and calculated neurotrophin/NT-3 ratios in AD-affected postmortem hippocampus, frontal and parietal cortex, and cerebellum, and compared them with age-matched control tissue (patients with AD/controls: hippocampus, 9/9 cases; frontal cortex, 19/9; parietal cortex, 8/5; and cerebellum, 5/7, respectively). We applied highly sensitive and specific enzyme-linked immunosorbent assays in rapid-autopsy-derived brain tissue (mean+/-SD postmortem interval, 2. 57+/-1.75 h, n=71) to minimize postmortem proteolytic activity. Levels of BDNF were significantly reduced in hippocampus and parietal cortex (P<.001, and P<.01) as well as BDNF/NT-3 ratios in frontal and parietal cortices (P<.05, and P<.01) in the group with AD compared with the control group. Levels of NGF and NGF/NT-3 ratio were significantly elevated in the group with AD compared with the control group in the hippocampus and frontal cortex (P<.001). Levels of NT-4/5 and the NT-4/NT-3 ratio were slightly reduced in hippocampus and cerebellum in the group with AD compared with the control group (P<.05). In contrast, the levels of NT-3 were unchanged in all brain regions investigated. Decreased levels of BDNF may constitute a lack of trophic support and, thus, may contribute to the degeneration of specific neuronal populations in the AD-affected brain, including the basal forebrain cholinergic system. Arch Neurol. 2000.

Knocking the NT4 gene into the BDNF locus rescues BDNF deficient mice and reveals distinct NT4 and BDNF activities.

To directly compare biological activities of the neurotrophins NT4 and BDNF in vivo, we replaced the BDNF coding sequence with the NT4 sequence in mice (Bdnfnt4-ki). Mice expressing NT4 in place of BDNF were viable, in contrast with BDNF null mutants, which die shortly after birth. Although the Bdnfnt4-ki/nt4-ki and wild-type Bdnf+/+ alleles yielded similar levels of NT4 and BDNF proteins, NT4 supported more sensory neurons than BDNF and promoted functional synapse formation in cultured hippocampal neurons. Homozygous Bdnfnt4-ki/nt4-ki mice showed reduced body weight, infertility and skin lesions, suggesting unique biological activities of NT4 in vivo. The distinct activities of NT4 and BDNF may result partly from differential activation of the TrkB receptor and its down-stream signals.

Decrease in the levels of NGF and BDNF in brains of mice fed a tryptophan-deficient diet.

The roles of dietary tryptophan (Trp) were evaluated in regulation of production of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin (NT)-3 in the various brain regions in ddY mice. Feeding the mice a Trp-deficient diet for 2 weeks significantly decreased in the hippocampal level of NGF but not those of BDNF and NT-3, as compared with feeding an adequate Trp diet. The mice fed excess Trp did not have different levels of any of these neurotrophins than in the mice fed an adequate Trp diet. The levels of BDNF in the cerebral cortex were also significantly lower in the mice fed on a Trp-deficient diet, while the levels of NGF and NT-3 in the region were not modulated upon feeding of the diet. The dietary Trp level had no significant effect on the levels of NGF, BDNF, or NT-3 in the entorhinal cortex nor septum of the mice. These results demonstrate that the brain levels of NGF and BDNF are dependent on the dietary content of tryptophan.

TrkB and Neurotrophin-4 Are Important for Development and Maintenance of Sympathetic Preganglionic Neurons Innervating the Adrenal Medulla

The adrenal medulla receives its major presynaptic input from sympathetic preganglionic neurons that are located in the intermediolateral (IML) column of the thoracic spinal cord. The neurotrophic factor concept would predict that these IML neurons receive trophic support from chromaffin cells in the adrenal medulla. We show here that adrenal chromaffin cells in the adult rat store neurotrophin (NT)-4, but do not synthesize or store detectable levels of BDNF or NT-3, respectively. Preganglionic neurons to the adrenal medulla identified by retrograde tracing with fast blue or Fluoro-Gold (FG) express TrkB mRNA. After unilateral destruction of the adrenal medulla, 24% of IML neurons, i.e., all neurons that are preganglionic to the adrenal medulla in spinal cord segments T7-T10, disappear. Administration of NT-4 in gelfoams (6 microgram) implanted into the medullectomized adrenal gland rescued all preganglionic neurons as evidenced by their presence after 4 weeks. NT-3 and cytochrome C were not effective. The action of NT-4 is accompanied by massive sprouting of axons in the vicinity of the NT-4 source as monitored by staining for acetylcholinesterase and synaptophysin immunoreactivity, suggesting that NT-4 may enlarge the terminal field of preganglionic nerves and enhance their access to trophic factors. Analysis of TrkB-deficient mice revealed degenerative changes in axon terminals on chromaffin cells. Furthermore, numbers of FG-labeled IML neurons in spinal cord segments T7-T10 of NT-4-deficient adult mice were significantly reduced. These data are consistent with the notion that NT-4 from chromaffin cells operates through TrkB receptors to regulate development and maintenance of the preganglionic innervation of the adrenal medulla.

Modulation of mRNA expression of the neurotrophins of the nerve growth factor family and their receptors in the septum and hippocampus of rats after transient postnatal thyroxine treatment. I. Expression of nerve growth factor, brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin 4 mRNA.

Early postnatal application of thyroid hormones to rats results in morphological changes in septum and hippocampus. Modulation in the expression of either neurotrophins and/or their receptors is postulated to be responsible for these effects. In the present study we tested whether thyroxine administration leads to changes in the expression of neurotrophins of the nerve growth factor (NGF) family. Newborn rats were treated daily with subcutaneous injections of thyroxine until postnatal day (P) 12 at maximum. The pups were killed at defined intervals from P2 to 21. The septal area and the hippocampi were analyzed using the reverse transcriptase-PCR method for quantitation of NGF, brain-derived neurotrophic factor (BDNF), NT-3, and NT-4 messenger RNA (mRNA) levels. In hippocampus of hyperthyroid rats, as compared to controls, we found higher levels of BDNF and NT-3 mRNA over the total investigation period, whereas in the septum a thyroxine-dependent increase in NT-3 mRNA expression was observed. In addition, significant thyroxine-induced effects were found for all variables (except for NGF in the septum) at particular postnatal days. From these data we conclude that modulation of neurotrophin expression is a possible mechanism for the morphological modifications within the hippocampal mossy fiber system and the septohippocampal cholinergic system.

Dopaminergic Transmitter Up-Regulation of Brain-Derived Neurotrophic Factor (BDNF) and Nerve Growth Factor (NGF) Synthesis in Mouse Astrocytes in Culture

We developed a highly sensitive enzyme immunoassay (EIA) system for brain-derived neurotrophic factor (BDNF) based on a biotin-streptavidin detection system capable of measuring concentrations as low as 1.0 pg/ml with high reproducibility. Using this EIA system, we examined the effect of dopaminergic transmitters such as dopamine and epinephrine on BDNF synthesis in mouse astrocytes in culture. These drugs had a stimulating effect on BDNF synthesis and showed a stronger promoting activity toward BDNF synthesis than toward nerve growth factor (NGF) synthesis. This is the first reported study in which BDNF synthesis was shown to be strongly stimulated by dopaminergic transmitter in mouse astrocytes. Then, we measured BDNF levels in the developing rat brain (striatum and midbrain). BDNF levels were relatively higher than NGF and NT-3 levels in these tissues. The BDNF level was high at the early stage in which neurons were proliferating, migrating, and differentiating, and it generally decreased as these cells matured.

1105 Inhibition of the speed of of cerebellar granule cell migration in vitro by NT-3-A time-lapse video microscopic analysis

In this study, we aimed to elucidate the restorative effects of olfactory epithelium neural stem cells (oe-NSCs) implantation on noise-induced hearing loss and establish their mechanism of action.To model hearing loss, rats were subjected to consecutive seven-day noise exposure. Then, oe-NSCs were implanted into cochlear tissue by retroauricular approach. Auditory brainstem response (ABR) method was used to evaluate the hearing function. Immunohistochemical staining was utilized to determine cell survival and migration of oe-NSCs. After IL-1β stimulation, nerve growth factor (NGF), neurotrophin-3 (NT-3), and NT-4 levels were evaluated in oe-NSCs. The protective action of oe-NSCs against hydrogen peroxide-induced cell injury was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL).oe-NSCs implantation into cochlear tissues ameliorated the noise-induced hearing impairment (p < 0.05). After implantation, green fluorescent cells were observed in an even suspension in the lymph fluid of the cochlea, and 65% of the GFP+ cells reached the cochlear duct wall three days after implantation, but did not expand to the Corti-organ. After IL-1β stimulation, olfactory epithelial stem cell increased their secretion of NGF and NT-3 (p < 0.05), but not that of NT-4. TUNEL assay results revealed that oe-NSCs co-culturing with injured neurons reduced the apoptotic cell death induced by hydrogen peroxide.After transplantation into the inner ear, oe-NSCs not only survived, but also migrated around the spiral ganglion neurons (SGNs) in Rosenthal's canal (RC). Hearing loss induced by noise exposure was restored after oe-NSCs implantation. Mechanically, oe-NSCs secreted NGF and NT-3, which likely contributed to the prevention of neuronal injury. This study provides novel data in support of the effective action of implanted oe-NSCs in the restoration of noise-induced hearing loss in a rat model.

Inhibition of the speed of of cerebellar granule cell migration in vitro by NT-3-A time-lapse video microscopic analysis

In this study, we aimed to elucidate the restorative effects of olfactory epithelium neural stem cells (oe-NSCs) implantation on noise-induced hearing loss and establish their mechanism of action.To model hearing loss, rats were subjected to consecutive seven-day noise exposure. Then, oe-NSCs were implanted into cochlear tissue by retroauricular approach. Auditory brainstem response (ABR) method was used to evaluate the hearing function. Immunohistochemical staining was utilized to determine cell survival and migration of oe-NSCs. After IL-1β stimulation, nerve growth factor (NGF), neurotrophin-3 (NT-3), and NT-4 levels were evaluated in oe-NSCs. The protective action of oe-NSCs against hydrogen peroxide-induced cell injury was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL).oe-NSCs implantation into cochlear tissues ameliorated the noise-induced hearing impairment (p < 0.05). After implantation, green fluorescent cells were observed in an even suspension in the lymph fluid of the cochlea, and 65% of the GFP+ cells reached the cochlear duct wall three days after implantation, but did not expand to the Corti-organ. After IL-1β stimulation, olfactory epithelial stem cell increased their secretion of NGF and NT-3 (p < 0.05), but not that of NT-4. TUNEL assay results revealed that oe-NSCs co-culturing with injured neurons reduced the apoptotic cell death induced by hydrogen peroxide.After transplantation into the inner ear, oe-NSCs not only survived, but also migrated around the spiral ganglion neurons (SGNs) in Rosenthal's canal (RC). Hearing loss induced by noise exposure was restored after oe-NSCs implantation. Mechanically, oe-NSCs secreted NGF and NT-3, which likely contributed to the prevention of neuronal injury. This study provides novel data in support of the effective action of implanted oe-NSCs in the restoration of noise-induced hearing loss in a rat model.

Age-related changes in levels of NGF, BDNF and NT-3 in the mouse brain

Age-related changes in levels of NGF, BDNF and NT-3 in the mouse brain