GM1 and ERK signaling in the aged brain.
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.
Mo
Lili
L
Department of Psychiatry, Division of Molecular Neuropsychopharmacology, Columbus, OH 43210, USA.
Ren
Qun
Q
Duchemin
Anne-Marie
AM
Neff
Norton H
NH
Hadjiconstantinou
Maria
M
D000367:Age Factors; D000375:Aging / Q000502:physiology*; D000818:Animals; D015153:Blotting, Western / Q000379:methods; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism; D004333:Drug Administration Routes; D004334:Drug Administration Schedule; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000145:classification / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology; D005677:G(M1) Ganglioside / Q000008:administration & dosage*; D066298:In Vitro Techniques; D008297:Male; D004676:Myelin Basic Protein / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*
D004791:Enzyme Inhibitors; D005419:Flavonoids; D004676:Myelin Basic Protein; D005677:G(M1) Ganglioside; D048049:Extracellular Signal-Regulated MAP Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one