Acute administration of the small-molecule p75(NTR) ligand does not prevent hippocampal neuron loss or development of spontaneous seizures after pilocarpine-induced status epilepticus.
J Neurosci Res
; 92(10): 1307-18, 2014 Oct.
Article
in En
| MEDLINE
| ID: mdl-24801281
ABSTRACT
Neurotrophins, such as brain-derived neurotrophic factor (BDNF), are initially expressed in a precursor form (e.g., pro-BDNF) and cleaved to form mature BDNF (mBDNF). After pilocarpine-induced status epilepticus (SE), increases in neurotrophins regulate a wide variety of cell-signaling pathways, including prosurvival and cell-death machinery in a receptor-specific manner. Pro-BDNF preferentially binds to the p75 neurotrophin receptor (p75(NTR) ), whereas mBDNF is the major ligand of the tropomyosin-related kinase receptor. To elucidate a potential role for p75(NTR) in acute stages of epileptogenesis, rats were injected prior to and at onset of SE with LM11A-31, a small-molecule ligand that binds to p75(NTR) to promote survival signaling and inhibit neuronal cell death. Modulation of early p75(NTR) signaling and its effects on electrographic SE, SE-induced neurodegeneration, and subsequent spontaneous seizures were examined after LM11A-31 administration. Despite an established neuroprotective effect of LM11A-31 in several animal models of neurodegenerative disorders (e.g., Alzheimer's disease, traumatic brain injury, and spinal cord injury), high-dose LM11A-31 administration prior to and at onset of SE did not reduce the intensity of electrographic SE, prevent SE-induced neuronal cell injury, or inhibit the progression of epileptogenesis. Further studies are required to understand the role of p75(NTR) activation during epileptogenesis and in seizure-induced cell injury in the hippocampus, among other potential cellular pathologies contributing to the onset of spontaneous seizures. Additional studies utilizing more prolonged treatment with LM11A-31 are required to reach a definite conclusion on its potential neuroprotective role in epilepsy.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Status Epilepticus
/
Morpholines
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Receptors, Nerve Growth Factor
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Isoleucine
/
Anticonvulsants
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
J Neurosci Res
Year:
2014
Document type:
Article