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Literature DB >> 20445044

Disruption of TrkB-mediated phospholipase Cgamma signaling inhibits limbic epileptogenesis.

Xiao Ping He¹, Enhui Pan, Carla Sciarretta, Liliana Minichiello, James O McNamara.

Abstract

The BDNF receptor, TrkB, is critical to limbic epileptogenesis, but the responsible downstream signaling pathways are unknown. We hypothesized that TrkB-dependent activation of phospholipase Cgamma1 (PLCgamma1) signaling is the key pathway and tested this in trkB(PLC/PLC) mice carrying a mutation (Y816F) that uncouples TrkB from PLCgamma1. Biochemical measures revealed activation of both TrkB and PLCgamma1 in hippocampi in the pilocarpine and kindling models in wild-type mice. PLCgamma1 activation was decreased in hippocampi isolated from trkB(PLC/PLC) compared with control mice. Epileptogenesis assessed by development of kindling was inhibited in trkB(PLC/PLC) compared with control mice. Long-term potentiation of the mossy fiber-CA3 pyramid synapse was impaired in slices of trkB(PLC/PLC) mice. We conclude that TrkB-dependent activation of PLCgamma1 signaling is an important molecular mechanism of limbic epileptogenesis. Elucidating signaling pathways activated by a cell membrane receptor in animal models of CNS disorders promises to reveal novel targets for specific and effective therapeutic intervention.

Entities: Chemical Disease Gene Mutation Species

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Year: 2010 PMID： 20445044 PMCID： PMC2872928 DOI： 10.1523/JNEUROSCI.5821-09.2010

Source DB: PubMed Journal: J Neurosci ISSN： 0270-6474 Impact factor: 6.167

47 in total

1. Differential mechanisms of transmission at three types of mossy fiber synapse.

Authors: K Toth; G Suares; J J Lawrence; E Philips-Tansey; C J McBain
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2. Hyperexcitability and epilepsy associated with disruption of the mouse neuronal-specific K-Cl cotransporter gene.

Authors: Nam-Sik Woo; Jianming Lu; Roger England; Robert McClellan; Samuel Dufour; David B Mount; Ariel Y Deutch; David M Lovinger; Eric Delpire
Journal: Hippocampus Date: 2002 Impact factor: 3.899

3. On the origin of interictal activity in human temporal lobe epilepsy in vitro.

Authors: Ivan Cohen; Vincent Navarro; Stéphane Clemenceau; Michel Baulac; Richard Miles
Journal: Science Date: 2002-11-15 Impact factor: 47.728

4. Altered mRNA expression for brain-derived neurotrophic factor and type II calcium/calmodulin-dependent protein kinase in the hippocampus of patients with intractable temporal lobe epilepsy.

Authors: K D Murray; P J Isackson; T A Eskin; M A King; S P Montesinos; L A Abraham; S N Roper
Journal: J Comp Neurol Date: 2000-03-20 Impact factor: 3.215

5. Cellular mechanisms regulating activity-dependent release of native brain-derived neurotrophic factor from hippocampal neurons.

Authors: Agnieszka Balkowiec; David M Katz
Journal: J Neurosci Date: 2002-12-01 Impact factor: 6.167

6. Structural plasticity of dentate granule cell mossy fibers during the development of limbic epilepsy.

Authors: Steve C Danzer; Xiaoping He; Andreas W Loepke; James O McNamara
Journal: Hippocampus Date: 2010-01 Impact factor: 3.899

7. Pilocarpine-induced epileptogenesis in the rat: impact of initial duration of status epilepticus on electrophysiological and neuropathological alterations.

Authors: Henrik Klitgaard; Alain Matagne; Jocelyne Vanneste-Goemaere; Doru-Georg Margineanu
Journal: Epilepsy Res Date: 2002-09 Impact factor: 3.045

8. Mechanism of TrkB-mediated hippocampal long-term potentiation.

Authors: Liliana Minichiello; Anna Maria Calella; Diego L Medina; Tobias Bonhoeffer; Rüdiger Klein; Martin Korte
Journal: Neuron Date: 2002-09-26 Impact factor: 17.173

9. Immunohistochemical evidence of seizure-induced activation of trkB receptors in the mossy fiber pathway of adult mouse hippocampus.

Authors: Xiao-Ping He; Liliana Minichiello; Rüdiger Klein; James O McNamara
Journal: J Neurosci Date: 2002-09-01 Impact factor: 6.167

10. BDNF-induced TrkB activation down-regulates the K+-Cl- cotransporter KCC2 and impairs neuronal Cl- extrusion.

Authors: Claudio Rivera; Hong Li; Judith Thomas-Crusells; Hannele Lahtinen; Tero Viitanen; Avtandil Nanobashvili; Zaal Kokaia; Matti S Airaksinen; Juha Voipio; Kai Kaila; Mart Saarma
Journal: J Cell Biol Date: 2002-12-09 Impact factor: 10.539

32 in total

1. Vesicular zinc promotes presynaptic and inhibits postsynaptic long-term potentiation of mossy fiber-CA3 synapse.

Authors: Enhui Pan; Xiao-an Zhang; Zhen Huang; Artur Krezel; Min Zhao; Christine E Tinberg; Stephen J Lippard; James O McNamara
Journal: Neuron Date: 2011-09-21 Impact factor: 17.173

2. RNA aptamer-based functional ligands of the neurotrophin receptor, TrkB.

Authors: Yang Zhong Huang; Frank J Hernandez; Bin Gu; Katie R Stockdale; Kishore Nanapaneni; Todd E Scheetz; Mark A Behlke; Andrew S Peek; Thomas Bair; Paloma H Giangrande; James O McNamara
Journal: Mol Pharmacol Date: 2012-06-29 Impact factor: 4.436

3. Dendritic trafficking of brain-derived neurotrophic factor mRNA: regulation by translin-dependent and -independent mechanisms.

Authors: Yen-Ching Wu; Rebecca Williamson; Zhi Li; Annalisa Vicario; Jerry Xu; Masataka Kasai; Yijuang Chern; Enrico Tongiorgi; Jay M Baraban
Journal: J Neurochem Date: 2011-01-20 Impact factor: 5.372

Disruption of TrkB-mediated phospholipase Cgamma signaling inhibits limbic epileptogenesis.

1. Differential mechanisms of transmission at three types of mossy fiber synapse.

2. Hyperexcitability and epilepsy associated with disruption of the mouse neuronal-specific K-Cl cotransporter gene.

3. On the origin of interictal activity in human temporal lobe epilepsy in vitro.

4. Altered mRNA expression for brain-derived neurotrophic factor and type II calcium/calmodulin-dependent protein kinase in the hippocampus of patients with intractable temporal lobe epilepsy.

5. Cellular mechanisms regulating activity-dependent release of native brain-derived neurotrophic factor from hippocampal neurons.

6. Structural plasticity of dentate granule cell mossy fibers during the development of limbic epilepsy.

7. Pilocarpine-induced epileptogenesis in the rat: impact of initial duration of status epilepticus on electrophysiological and neuropathological alterations.

8. Mechanism of TrkB-mediated hippocampal long-term potentiation.

9. Immunohistochemical evidence of seizure-induced activation of trkB receptors in the mossy fiber pathway of adult mouse hippocampus.

10. BDNF-induced TrkB activation down-regulates the K+-Cl- cotransporter KCC2 and impairs neuronal Cl- extrusion.

1. Vesicular zinc promotes presynaptic and inhibits postsynaptic long-term potentiation of mossy fiber-CA3 synapse.

2. RNA aptamer-based functional ligands of the neurotrophin receptor, TrkB.

3. Dendritic trafficking of brain-derived neurotrophic factor mRNA: regulation by translin-dependent and -independent mechanisms.

4. A Peptide Uncoupling BDNF Receptor TrkB from Phospholipase Cγ1 Prevents Epilepsy Induced by Status Epilepticus.

5. TRPC3 channels play a critical role in the theta component of pilocarpine-induced status epilepticus in mice.

6. TrkB-Shc Signaling Protects against Hippocampal Injury Following Status Epilepticus.

7. Impairment of kindling development in phospholipase Cγ1 heterozygous mice.

8. p75 regulates Purkinje cell firing by modulating SK channel activity through Rac1.

Review 9. Targeting BDNF/TrkB pathways for preventing or suppressing epilepsy.

10. The auxiliary subunit KChIP2 is an essential regulator of homeostatic excitability.