Alterations of cerebellar mRNA specific for BDNF, p75NTR, and TrkB receptor isoforms occur within hours of ethanol administration to 4-day-old rat pups

2004 ◽  
Vol 151 (1-2) ◽  
pp. 99-109 ◽  
Author(s):  
Yun Ge ◽  
Scott M Belcher ◽  
Kim E Light
Keyword(s):  
Ethanol Administration ◽  
Trkb Receptor ◽  
Rat Pups ◽  
Receptor Isoforms

scholarly journals Expression of TrkB receptor isoforms in the developing avian visual system

1996 ◽  
Vol 16 (5) ◽  
pp. 1740-1752 ◽  
Author(s):  
AS Garner ◽  
HJ Menegay ◽  
KL Boeshore ◽  
XY Xie ◽  
JM Voci ◽  
...  
Keyword(s):  
Visual System ◽  
Trkb Receptor ◽  
Receptor Isoforms ◽  
Avian Visual System

scholarly journals NT-4 attenuates neuroinflammation via TrkB/PI3K/FoxO1 pathway after germinal matrix hemorrhage in neonatal rats

2019 ◽  
Author(s):  
Tianyi Wang ◽  
Junyi Zhang ◽  
Peng Li ◽  
Yan Ding ◽  
Jiping Tang ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Inflammatory Factors ◽  
Neonatal Rats ◽  
Germinal Matrix ◽  
Germinal Matrix Hemorrhage ◽  
Trkb Receptor ◽  
Rat Pups ◽  
Short And Long Term ◽  
Pro Inflammatory Cytokines

Abstract Background: Neuroinflammation plays an important role in pathogenesis of germinal matrix hemorrhage (GMH). Neurotrophin-4 (NT-4) is a member of the neurotrophin family, and it interacts with the tyrosine kinase B (TrkB) receptor. It has been studied that NT-4 has neuroprotective effects following cerebral ischemia. We aimed to investigate the neuroprotective function of NT-4 and it’s high affinity receptor TrkB as well as its downstream mediator phosphatidylinositol-3-kinases (PI3K)/protein kinase B (Akt)/Forkhead box protein O1 (FoxO1) following GMH in neonatal rats, with a specific focus on inflammation. Methods: GMH was induced by intraparenchymal injection of bacterial collagenase (0.3U) in P7 rat pups. A total of 163 seven-day-old pups were used in this study. The recombinant human NT-4 was administered intranasally at 1 hour after the collagenase injection. The selective TrkB antagonist ANA-12, selective PI3K inhibitor LY294002 and FoxO1 activating CRISPR were administered intracerebroventricularly at 24 hours prior to NT-4 treatment to investigate the potential mechanism. Short-and-long-term neurobehavior assessments, immunofluorescence staining, Nissl’s staining and Western blot were performed. Results：The expression of p-TrkB increased after GMH with a peak at day3. The TrkB receptor was expressed by neurons, microglia, and astrocytes. The administration of rh-NT-4 increased phosphorylation of TrkB, expression of PI3K, phosphorylation of Akt and decreased FoxO1, IL-1beta and IL-6 levels. Selective inhibition of TrkB/PI3K/Akt signaling in microglia increased the expression levels of FoxO1 and pro-inflammatory cytokines. The use of FoxO1 activation CRISPR increased the expression of IL-6, suggesting that FoxO1 might potentially induce pro-inflammatory factors. These results demonstrated that PI3K/Akt/FoxO1 may be the downstream pathway of TrkB phosphorylation. The rat pups treated with rh-NT-4 performed better than untreated animals both in short-and-long-term behavior test. Conclusion：These data showed that rh-NT-4 can reduce the expression of pro-inflammatory cytokines, improve neurological function, attenuate neuroinflammation and post-hemorrhagic hydrocephalus after GMH by promoting TrkB/PI3K/Akt/FoxO1 pathway. These results indicated that rh-NT-4 could be a promising therapeutic target to ameliorate neuroinflammation and hydrocephalus after GMH or other similar brain injuries.

scholarly journals Signal Transduction Mediated by the Truncated trkB Receptor Isoforms, trkB.T1 and trkB.T2

1997 ◽  
Vol 17 (8) ◽  
pp. 2683-2690 ◽  
Author(s):  
Gregory T. Baxter ◽  
Monte J. Radeke ◽  
Richard C. Kuo ◽  
Victoria Makrides ◽  
Beth Hinkle ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Trkb Receptor ◽  
Receptor Isoforms

Melatonin prevents oxidative damage induced by maternal ethanol administration and reduces homocysteine in the cerebellum of rat pups

2015 ◽  
Vol 287 ◽  
pp. 215-225 ◽  
Author(s):  
Farzaneh Bagheri ◽  
Iran Goudarzi ◽  
Taghi Lashkarbolouki ◽  
Mahmoud Elahdadi Salmani
Keyword(s):  
Oxidative Damage ◽  
Ethanol Administration ◽  
Rat Pups

scholarly journals Function and Mechanisms of Truncated BDNF Receptor TrkB.T1 in Neuropathic Pain

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1194 ◽  
Author(s):  
Tuoxin Cao ◽  
Jessica J. Matyas ◽  
Cynthia L. Renn ◽  
Alan I. Faden ◽  
Susan G. Dorsey ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Therapeutic Potential ◽  
Recovery Of Function ◽  
Kinase Domain ◽  
Cns Injury ◽  
Trkb Receptor ◽  
Receptor Isoforms ◽  
The Central Nervous System ◽  
Injury Models

Brain-derived neurotrophic factor (BDNF), a major focus for regenerative therapeutics, has been lauded for its pro-survival characteristics and involvement in both development and recovery of function within the central nervous system (CNS). However, studies of tyrosine receptor kinase B (TrkB), a major receptor for BDNF, indicate that certain effects of the TrkB receptor in response to disease or injury may be maladaptive. More specifically, imbalance among TrkB receptor isoforms appears to contribute to aberrant signaling and hyperpathic pain. A truncated isoform of the receptor, TrkB.T1, lacks the intracellular kinase domain of the full length receptor and is up-regulated in multiple CNS injury models. Such up-regulation is associated with hyperpathic pain, and TrkB.T1 inhibition reduces neuropathic pain in various experimental paradigms. Deletion of TrkB.T1 also limits astrocyte changes in vitro, including proliferation, migration, and activation. Mechanistically, TrkB.T1 is believed to act through release of intracellular calcium in astrocytes, as well as through interactions with neurotrophins, leading to cell cycle activation. Together, these studies support a potential role for astrocytic TrkB.T1 in hyperpathic pain and suggest that targeted strategies directed at this receptor may have therapeutic potential.

Balanced expression of various TrkB receptor isoforms from the Ntrk2 gene locus in the mouse nervous system

2008 ◽  
Vol 39 (3) ◽  
pp. 465-477 ◽  
Author(s):  
Haruko Kumanogoh ◽  
Junko Asami ◽  
Shun Nakamura ◽  
Takayoshi Inoue
Keyword(s):  
Nervous System ◽  
Gene Locus ◽  
Trkb Receptor ◽  
Receptor Isoforms

scholarly journals NT-4 attenuates neuroinflammation via TrkB/PI3K/FoxO1 pathway after germinal matrix hemorrhage in neonatal rats

2020 ◽  
Author(s):  
Tianyi Wang ◽  
Junyi Zhang ◽  
Peng Li ◽  
Yan Ding ◽  
Jiping Tang ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Inflammatory Factors ◽  
Neonatal Rats ◽  
Germinal Matrix ◽  
Germinal Matrix Hemorrhage ◽  
Trkb Receptor ◽  
Rat Pups ◽  
Short And Long Term ◽  
Pro Inflammatory Cytokines

Abstract Background: Neuroinflammation plays an important role in pathogenesis of germinal matrix hemorrhage (GMH). Neurotrophin-4 (NT-4) is a member of the neurotrophin family, and it interacts with the tyrosine kinase B (TrkB) receptor. It has been studied that NT-4 has neuroprotective effects following cerebral ischemia. We aimed to investigate the neuroprotective function of NT-4 and it’s high affinity receptor TrkB as well as its downstream mediator phosphatidylinositol-3-kinases (PI3K)/protein kinase B (Akt)/Forkhead box protein O1 (FoxO1) following GMH in neonatal rats, with a specific focus on inflammation. Methods: GMH was induced by intraparenchymal injection of bacterial collagenase (0.3U) in P7 rat pups. A total of 163 seven-day-old pups were used in this study. The recombinant human NT-4 was administered intranasally at 1 hour after the collagenase injection. The selective TrkB antagonist ANA-12, selective PI3K inhibitor LY294002 and FoxO1 activating CRISPR were administered intracerebroventricularly at 24 hours prior to NT-4 treatment to investigate the potential mechanism. Short-and-long-term neurobehavior assessments, immunofluorescence staining, Nissl’s staining and Western blot were performed. Results ： The expression of p-TrkB increased after GMH with a peak at day3. The TrkB receptor was expressed by neurons, microglia, and astrocytes. The administration of rh-NT-4 increased phosphorylation of TrkB, expression of PI3K, phosphorylation of Akt and decreased FoxO1, IL-1beta and IL-6 levels. Selective inhibition of TrkB/PI3K/Akt signaling in microglia increased the expression levels of FoxO1 and pro-inflammatory cytokines. The use of FoxO1 activation CRISPR increased the expression of IL-6, suggesting that FoxO1 might potentially induce pro-inflammatory factors. These results demonstrated that PI3K/Akt/FoxO1 may be the downstream pathway of TrkB phosphorylation. The rat pups treated with rh-NT-4 performed better than untreated animals both in short-and-long-term behavior test. Conclusion： These data showed that rh-NT-4 can reduce the expression of pro-inflammatory cytokines, improve neurological function, attenuate neuroinflammation and post-hemorrhagic hydrocephalus after GMH by promoting TrkB/PI3K/Akt/FoxO1 pathway. These results indicated that rh-NT-4 could be a promising therapeutic target to ameliorate neuroinflammation and hydrocephalus after GMH or other similar brain injuries.

scholarly journals NT-4 attenuates neuroinflammation via TrkB/PI3K/FoxO1 pathway after germinal matrix hemorrhage in neonatal rats

2020 ◽  
Author(s):  
Tianyi Wang ◽  
Junyi Zhang ◽  
Peng Li ◽  
Yan Ding ◽  
Jiping Tang ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Inflammatory Factors ◽  
Neonatal Rats ◽  
Germinal Matrix ◽  
Germinal Matrix Hemorrhage ◽  
Trkb Receptor ◽  
Rat Pups ◽  
Short And Long Term ◽  
Pro Inflammatory Cytokines

Abstract Background: Neuroinflammation plays an important role in pathogenesis of germinal matrix hemorrhage (GMH). Neurotrophin-4 (NT-4) is a member of the neurotrophin family, and it interacts with the tyrosine kinase B (TrkB) receptor. It has been studied that NT-4 has neuroprotective effects following cerebral ischemia. We aimed to investigate the neuroprotective function of NT-4 and it’s high affinity receptor TrkB as well as its downstream mediator phosphatidylinositol-3-kinases (PI3K)/protein kinase B (Akt)/Forkhead box protein O1 (FoxO1) following GMH in neonatal rats, with a specific focus on inflammation. Methods: GMH was induced by intraparenchymal injection of bacterial collagenase (0.3U) in P7 rat pups. A total of 163 seven-day-old pups were used in this study. The recombinant human NT-4 was administered intranasally at 1 hour after the collagenase injection. The selective TrkB antagonist ANA-12, selective PI3K inhibitor LY294002 and FoxO1 activating CRISPR were administered intracerebroventricularly at 24 hours prior to NT-4 treatment to investigate the potential mechanism. Short-and-long-term neurobehavior assessments, immunofluorescence staining, Nissl’s staining and Western blot were performed. Results ： The expression of p-TrkB increased after GMH with a peak at day3. The TrkB receptor was expressed by neurons, microglia, and astrocytes. The administration of rh-NT-4 increased phosphorylation of TrkB, expression of PI3K, phosphorylation of Akt and decreased FoxO1, IL-1beta and IL-6 levels. Selective inhibition of TrkB/PI3K/Akt signaling in microglia increased the expression levels of FoxO1 and pro-inflammatory cytokines. The use of FoxO1 activation CRISPR increased the expression of IL-6, suggesting that FoxO1 might potentially induce pro-inflammatory factors. These results demonstrated that PI3K/Akt/FoxO1 may be the downstream pathway of TrkB phosphorylation. The rat pups treated with rh-NT-4 performed better than untreated animals both in short-and-long-term behavior test. Conclusion： These data showed that rh-NT-4 can reduce the expression of pro-inflammatory cytokines, improve neurological function, attenuate neuroinflammation and post-hemorrhagic hydrocephalus after GMH by promoting TrkB/PI3K/Akt/FoxO1 pathway. These results indicated that rh-NT-4 could be a promising therapeutic target to ameliorate neuroinflammation and hydrocephalus after GMH or other similar brain injuries.

Sign in / Sign up

Export Citation Format

Share Document