Neurobiology of Aging 31 (2010) 129–142 Preserved memory capacities in aged Lou/C/Jall rats M. Kollen a,1 , A. St´ ephan a,1 , A. Faivre-Bauman a , C. Loudes a , P.-M. Sinet a , J. Alliot b , J.M. Billard a , J. Epelbaum a , P. Dutar a , A. Jouvenceau a,∗ a Centre de Psychiatrie et de Neurosciences, UMR 894 Inserm, Universit´ e Paris Descartes, Facult´ e de M´ edecine, 2 ter rue d’Al´ esia, F-75014, Paris, France b Laboratoire de Neuroendocrinologie du Vieillissement, Complexe Scientifique des C´ ezeaux, Universit´ e Blaise Pascal, Clermont-Ferrand, France Received 14 November 2007; received in revised form 10 March 2008; accepted 14 March 2008 Available online 6 May 2008 Abstract Although memory impairments are a hallmark of aging, the degree of deficit varies across animal models, and is likely to reflect different states of deterioration in metabolic and endocrinological properties. This study investigated memory-related processes in young (3–4 months) and old (24 months) Sprague–Dawley rats (SD), which develop age-linked pathologies such as obesity or insulin-resistance and Lou/C/Jall rats, which do not develop such impairments. In short- and long-term memory recognition tasks, old Lou/C/Jall rats were never impaired whereas old SD rats were deficient at 1 and 24 h latencies. The expression of N-methyl-d-aspartate receptors (NMDAR)-mediated synaptic plasticity in CA1 hippocampal networks shifted towards lower activity values in old Lou/C/Jall rats whereas long-term potentiation was impaired in age-matched SD rats. Age-related decrease in NR2A subunits occurred in both strains, extended to NR2B, NR1 and GluR1 subunits in older animals (28 months) but only in SD rats. Therefore, the Lou/C/Jall rats can be considered as a model of healthy aging, not only in terms of its preserved metabolism, but also in terms of cognition and synaptic plasticity. © 2008 Elsevier Inc. All rights reserved. Keywords: Aging; Memory; Synaptic plasticity; NMDA receptor; Hippocampus; Caloric restriction 1. Introduction Aging is commonly associated with a wide variety of impaired biological functions. Among these, a decline in cog- nitive functions is generally observed. For example, elderly humans often display slower learning abilities and quicker forgetting (Grady and Craik, 2000). Accumulated evidence indicates that, on average, cognition and memory decline can occur during normal aging, i.e., in the absence of neurode- generative diseases (Barnes, 1979; Barnes and McNaughton, ∗ Corresponding author at: Centre de Psychiatrie et Neuroscience U894, Facult´ e de m´ edecine, Universit´ e Paris Descartes, 2 ter rue d’Al´ esia, 75014 Paris, France. Tel.: +33 1 40 78 86 03; fax: +33 1 45 80 72 93. E-mail addresses: Kollen@broca.inserm.fr (M. Kollen), Stephan@broca.inserm.fr (A. St´ ephan), Loudes@broca.inserm.fr (C. Loudes), Sinet@broca.inserm.fr (P.-M. Sinet), Josette.ALLIOT@univ-bpclermont.fr (J. Alliot), Billard@broca.inserm.fr (J.M. Billard), Epelbaum@broca.inserm.fr (J. Epelbaum), Dutar@broca.inserm.fr (P. Dutar), anne.jouvenceau@inserm.fr (A. Jouvenceau). 1 These authors contributed equally to this work. 1985). Both pharmacological and behavioural interventions have been developed to reduce the cognitive decline in the elderly with, unfortunately, limited efficacy. Diet and caloric intake are key to comfortable and healthy aging, since metabolic disorders such as increased adiposity and insulin-resistance occur with age (Frisard and Ravussin, 2006). Indeed, age-related brain dysfunctions induced by stress and inflammatory responses or enhanced neurotrophic expression, can be counteracted by a decreased caloric food intake via dietary restriction (Mattson et al., 2003). Although caloric intake restriction is now broadly used as a means of increasing lifespan, its efficacy in preventing memory deficits remains debated in the literature, likely reflecting differences in feeding schedules (Beatty et al., 1987; Bellush et al., 1996; Hansalik et al., 2006; Ingram et al., 1987; Markowska, 1999; Markowska and Savonenko, 2002; Pitsikas and Algeri, 1992; Stewart et al., 1989; Yanai et al., 2004). The inbred Lou/C rat, has recently been described as a model of healthy aging (Alliot et al., 2002) with a median lifespan (50% of survivors) of 29 months as compared to 24 months for Sprague–Dawley 0197-4580/$ – see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.neurobiolaging.2008.03.010