title: Protein kinase Mζ-dependent maintenance of GluA2 at the synapse: a possible target for preventing or treating age-related memory decline?
abstract: Age-related functional alterations in the perforant path projection from the entorhinal cortex to the dentate gyrus (DG) of the hippocampus play a major role in age-related memory impairments, but little is known about the molecular mechanisms responsible for these changes. In a recent interesting study, Hara and colleagues (J Neurosci 2012;32:7336-7344) tested young and aged monkeys on the visual recognition memory test "delayed nonmatching-to-sample" (DNMS). Then they performed electron microscopy immunocytochemistry in the hippocampal DG to determine the subcellular localization of the GluA2 subunit of the glutamate α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPAR) and protein kinase Mζ (PKMζ), which promotes memory storage by regulating GluA2-containing AMPAR trafficking. The results obtained suggest that age-related deficits in visual recognition memory are coupled with impairment in PKMζ-dependent maintenance of GluA2 at the synapse. Together with previous evidence of the critical role of PKMζ in memory consolidation, these data render this enzyme an attractive potential therapeutic target for preventing or treating age-related memory decline, and support the view that the pharmacological manipulation of AMPAR trafficking in the synapses may provide new insights in the search of memory enhancers for aged individuals, including those affected by Alzheimer disease.
authors.affiliation: Department for Life Quality Studies, University of Bologna, 40127 Bologna, Italy. giorgio.aicardi@unibo.it
authors.forename: Giorgio
authors.initials: G
authors.lastname: Aicardi
mesh_terms: D000375:Aging / Q000473:pathology*; D000818:Animals; D018891:Dentate Gyrus / Q000503:physiopathology; D006801:Humans; D008569:Memory Disorders / Q000503:physiopathology / Q000517:prevention & control* / Q000628:therapy*; D011493:Protein Kinase C / Q000378:metabolism*; D018091:Receptors, AMPA / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*
chemical_list: D018091:Receptors, AMPA; D011493:Protein Kinase C; C104722:glutamate receptor ionotropic, AMPA 2