A putative mechanism of age-related synaptic dysfunction based on the impact of IGF-1 receptor signaling on synaptic CaMKIIα phosphorylation

Insulin-like growth factor 1 receptor (IGF-1R) signaling regulates the activity and phosphorylation of downstream kinases linked to inflammation, neurodevelopment, aging and synaptic function. In addition to the control of Ca2+ currents, IGF-1R signaling modulates the activity of calcium-calmodulin-...

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Detalles Bibliográficos
Autores principales: Ogundele, Olalekan Michael, Pardo, Joaquín, Francis, Joseph, Goya, Rodolfo Gustavo, Lee, Charles C.
Formato: Articulo
Lenguaje:Inglés
Publicado: 2018
Materias:
Biología
Aging
CaMKIIα
IGF-1/IGF-1R
MAPK/ErK
KCa2.2
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/104535
http://hdl.handle.net/11336/96929
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-104535
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Biología
Aging
CaMKIIα
IGF-1/IGF-1R
MAPK/ErK
KCa2.2
spellingShingle Biología
Aging
CaMKIIα
IGF-1/IGF-1R
MAPK/ErK
KCa2.2
Ogundele, Olalekan Michael
Pardo, Joaquín
Francis, Joseph
Goya, Rodolfo Gustavo
Lee, Charles C.
A putative mechanism of age-related synaptic dysfunction based on the impact of IGF-1 receptor signaling on synaptic CaMKIIα phosphorylation
topic_facet Biología
Aging
CaMKIIα
IGF-1/IGF-1R
MAPK/ErK
KCa2.2
description Insulin-like growth factor 1 receptor (IGF-1R) signaling regulates the activity and phosphorylation of downstream kinases linked to inflammation, neurodevelopment, aging and synaptic function. In addition to the control of Ca2+ currents, IGF-1R signaling modulates the activity of calcium-calmodulin-dependent kinase 2 alpha (CaMKIIα) and mitogen activated protein kinase (MAPK/ErK) through multiple signaling pathways. These proteins (CaMKIIα and MAPK) regulate Ca2+ movement and long-term potentiation (LTP). Since IGF-1R controls the synaptic activity of Ca2+, CaMKIIα and MAPK signaling, the possible mechanism through which an age-dependent change in IGF-1R can alter the synaptic expression and phosphorylation of these proteins in aging needs to be investigated. In this study, we evaluated the relationship between an age-dependent change in brain IGF-1R and phosphorylation of CaMKIIα/MAPK. Furthermore, we elucidated possible mechanisms through which dysregulated CaMKIIα/MAPK interaction may be linked to a change in neurotransmitter processing and synaptic function. Male C57BL/6 VGAT-Venus mice at postnatal days 80 (P80), 365 and 730 were used to study age-related neural changes in two brain regions associated with cognitive function: hippocampus and prefrontal cortex (PFC). By means of high throughput confocal imaging and quantitative immunoblotting, we evaluated the distribution and expression of IGF-1, IGF-1R, CaMKIIα, p-CaMKIIα, MAPK and p-MAPK in whole brain lysate, hippocampus and cortex. Furthermore, we compared protein expression patterns and regional changes at P80, P365 and P730. Ultimately, we determined the relative phosphorylation pattern of CaMKIIα and MAPK through quantification of neural p-CaMKIIα and p-MAPK/ErK, and IGF-1R expression for P80, P365 and P730 brain samples. In addition to a change in synaptic function, our results show a decrease in neural IGF-1/IGF-1R expression in whole brain, hippocampus and cortex of aged mice. This was associated with a significant upregulation of phosphorylated neural MAPK (p-MAPK) and decrease in total brain CaMKIIα (i.e., CaMKIIα and p-CaMKIIα) in the aged brain. Taken together, we showed that brain aging is associated with a change in neural IGF-1/IGF-1R expression and may be linked to a change in phosphorylation of synaptic kinases (CaMKIIα and MAPK) that are involved in the modulation of LTP.
format Articulo
Articulo
author Ogundele, Olalekan Michael
Pardo, Joaquín
Francis, Joseph
Goya, Rodolfo Gustavo
Lee, Charles C.
author_facet Ogundele, Olalekan Michael
Pardo, Joaquín
Francis, Joseph
Goya, Rodolfo Gustavo
Lee, Charles C.
author_sort Ogundele, Olalekan Michael
title A putative mechanism of age-related synaptic dysfunction based on the impact of IGF-1 receptor signaling on synaptic CaMKIIα phosphorylation
title_short A putative mechanism of age-related synaptic dysfunction based on the impact of IGF-1 receptor signaling on synaptic CaMKIIα phosphorylation
title_full A putative mechanism of age-related synaptic dysfunction based on the impact of IGF-1 receptor signaling on synaptic CaMKIIα phosphorylation
title_fullStr A putative mechanism of age-related synaptic dysfunction based on the impact of IGF-1 receptor signaling on synaptic CaMKIIα phosphorylation
title_full_unstemmed A putative mechanism of age-related synaptic dysfunction based on the impact of IGF-1 receptor signaling on synaptic CaMKIIα phosphorylation
title_sort putative mechanism of age-related synaptic dysfunction based on the impact of igf-1 receptor signaling on synaptic camkiiα phosphorylation
publishDate 2018
url http://sedici.unlp.edu.ar/handle/10915/104535
http://hdl.handle.net/11336/96929
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