GM1 and ERK signaling in the aged brain.

Abstract:

:We investigated the ability of GM1 to induce phosphorylation/activation of the extracellular-regulated protein kinases (ERKs) in the striatum, hippocampus and frontal cortex of aged male Sprague-Dawley rats. Three different treatment paradigms were used: a single application of GM1 to brain slices in situ, a single intracerebroventricular (icv) administration of GM1 in vivo, and chronic administration of GM1 in vivo. In situ, GM1 induced a rapid and transient activation of ERK1 and ERK 2 in both young and aged rats, and a similar effect was observed after stimulation with the neurotrophins NGF and BDNF. The aged brain appeared to respond more robustly to neurotrophic stimulation with the pERK2 response being significantly greater in the hippocampus and frontal cortex. Acute icv administration of GM1 resulted in short-lasting phosphorylation of ERKs in both aged groups, while chronic administration of GM1 induced a protracted phosphorylation of ERKs. Following chronic GM1 treatment, pERK2 levels in the aged hippocampus were elevated over young control animals. In agreement with reports that GM1 phosphorylates TrkA in vitro or in situ, treatment with GM1 increased the phosphorylation of TrkA in hippocampus of both young and aged animals. These observations indicate that the aged brain maintains the ability to respond to neurotrophic stimuli and put forward the proposition that the ERK cascade is associated with the action(s) of GM1 ganglioside in vivo.

journal_name

Brain Res

journal_title

Brain research

authors

Mo L,Ren Q,Duchemin AM,Neff NH,Hadjiconstantinou M

doi

10.1016/j.brainres.2005.06.068

subject

Has Abstract

pub_date

2005-08-30 00:00:00

pages

125-34

issue

2

eissn

0006-8993

issn

1872-6240

pii

S0006-8993(05)00995-9

journal_volume

1054

pub_type

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