title: Enhanced LTP in aged rats: Detrimental or compensatory?
abstract: Age-dependent memory deterioration has been well documented and yet an increase in rat hippocampal LTP upon aging has been reported. This poses the question of whether the enhanced LTP is a cause or an attempt to compensate the memory deficits described in aged rats. Hippocampal slices from young, adult and aged Wistar rats were pre-incubated, with an NMDA receptor (NMDAR) antagonist, memantine (1 μM, 4 h), and hippocampal LTP was evaluated. The results show that memantine significantly decreases the larger LTP magnitude recorded in hippocampal slices from aged rats without compromising LTP recorded in slices from young and adult animals. To unveil the impact of in vivo administration of memantine, different doses (1, 5 and 10 mg/kg/day) or saline vehicle solution were intraperitoneally administered, for 15-20 days, to both young and aged animals. Memantine did not significantly affect neither the place learning of young animals, evaluated by Morris Water Maze, nor LTP recorded from hippocampal slices from the same group of animals. However, memantine (5 and 10 mg/kg/day) significantly decreased the large LTP recorded in hippocampal slices from aged animals. Moreover, aged animals treated with memantine (10 mg/kg/day) showed a significantly compromised place learning when compared to aged control animals. Overall, these results suggest that the larger LTP observed in aged animals is a compensatory phenomenon, rather than pathological. The finding that age-dependent blockade of LTP by a NMDAR antagonist leads to learning deficits, implies that the increased LTP observed upon aging may be playing an important role in the learning process.
authors.affiliation: Instituto de Farmacologia e Neurociências, Faculdade de Medicina de Lisboa, Universidade de Lisboa, Portugal; Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Universidade de Lisboa, Portugal. Electronic address: julia13pinho@gmail.com.
authors.forename: Júlia
authors.initials: J
authors.lastname: Pinho
authors.affiliation: Instituto de Farmacologia e Neurociências, Faculdade de Medicina de Lisboa, Universidade de Lisboa, Portugal; Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Universidade de Lisboa, Portugal. Electronic address: rubenduque@gmail.com.
authors.forename: Ruben
authors.initials: R
authors.lastname: Vale
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Universidade de Lisboa, Portugal. Electronic address: vanialnbatalha@gmail.com.
authors.forename: Vânia L
authors.initials: VL
authors.lastname: Batalha
authors.affiliation: Instituto de Farmacologia e Neurociências, Faculdade de Medicina de Lisboa, Universidade de Lisboa, Portugal; Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Universidade de Lisboa, Portugal. Electronic address: arcosntenla@gmail.com.
authors.forename: Ana Rita
authors.initials: AR
authors.lastname: Costenla
authors.affiliation: Instituto de Farmacologia e Neurociências, Faculdade de Medicina de Lisboa, Universidade de Lisboa, Portugal; Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Universidade de Lisboa, Portugal. Electronic address: r.alice@gmail.com.
authors.forename: Raquel
authors.initials: R
authors.lastname: Dias
authors.affiliation: Instituto de Farmacologia e Neurociências, Faculdade de Medicina de Lisboa, Universidade de Lisboa, Portugal; Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Universidade de Lisboa, Portugal. Electronic address: d.rombo@gmail.com.
authors.forename: Diogo
authors.initials: D
authors.lastname: Rombo
authors.affiliation: Instituto de Farmacologia e Neurociências, Faculdade de Medicina de Lisboa, Universidade de Lisboa, Portugal; Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Universidade de Lisboa, Portugal. Electronic address: anaseb@medicina.ulisboa.pt.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Sebastião
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Universidade de Lisboa, Portugal. Electronic address: mendoca@medicina.ulisboa.pt.
authors.forename: Alexandre
authors.initials: A
authors.lastname: de Mendonça
authors.affiliation: Instituto de Farmacologia e Neurociências, Faculdade de Medicina de Lisboa, Universidade de Lisboa, Portugal; Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Universidade de Lisboa, Portugal. Electronic address: diogenes@medicina.ulisboa.pt.
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Diógenes
mesh_terms: D000375:Aging; D000818:Animals; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008559:Memantine / Q000008:administration & dosage* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000502:physiology; D065853:Spatial Learning / Q000187:drug effects
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D008559:Memantine
keywords: Aging; Hippocampus; Long-term potentiation; Spatial learning; Watermaze