Down-regulation of AMPA receptors and long-term potentiation during early epileptogenesis.
Epilepsy Behav
; 124: 108320, 2021 Sep 27.
Article
en En
| MEDLINE
| ID: mdl-34592633
ABSTRACT
Epilepsy is a brain disorder characterized by the occurrence of recurrent spontaneous seizures. Behavioral disorders and altered cognition are frequent comorbidities affecting the quality of life of people with epilepsy. These impairments are undoubtedly multifactorial and the specific mechanisms underlying these comorbidities are largely unknown. Long-lasting alterations in synaptic strength due to changes in expression, phosphorylation, or function of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors (AMPARs) have been associated with alterations in neuronal synaptic plasticity. In particular, alterations in hippocampal long-term potentiation (LTP), a well-accepted model of learning and memory, have been associated with altered cognition in epilepsy. Here, we analyzed the effects of pilocarpine-induced status epilepticus (SE) on AMPARs to determine if alterations in AMPAR signaling might be one of the mechanisms contributing to altered cognition during epilepsy. We found alterations in the phosphorylation and plasma membrane expression of AMPARs. In addition, we detected altered expression of GRIP, a key scaffolding protein involved in the proper distribution of AMPARs at the neuronal cell surface. Interestingly, a functional analysis revealed that these molecular changes are linked to impaired LTP. Together, these observations suggest that seizure-induced alterations in the molecular machinery regulating AMPARs likely impact the neuron's ability to support synaptic plasticity that is required for learning and memory.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Aspecto:
Patient_preference
Idioma:
En
Revista:
Epilepsy Behav
Asunto de la revista:
CIENCIAS DO COMPORTAMENTO
/
NEUROLOGIA
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos