Caloric restriction increases learning consolidation and facilitates synaptic plasticity through mechanisms dependent on NR2B subunits of the NMDA receptor.
One of the main focal points of aging research is the search for treatments that will prevent or ameliorate the learning and memory deficiencies associated with aging. Here we have examined the effects of maintaining mature mice on a long-term intermittent fasting diet (L-IFD). We found that L-IFD enhances learning and consolidation processes. We also assessed the long-term changes in synaptic efficiency in these animals. L-IFD mice showed an increase in low-theta-band oscillations, paired-pulse facilitation, and facilitation of long-term synaptic plasticity in the hippocampus with respect to mice fed ad libitum. In addition, we found an increase in the expression of the NMDA receptor subunit NR2B in some brain areas of L-IFD mice. Specific antagonism of this subunit in the hippocampus reversed the beneficial effects of L-IFD. These data provide a molecular and cellular mechanism by which L-IFD may enhance cognition, ameliorating some aging-associated cognitive deficits.
Fontán-Lozano
Angela
A
División de Neurociencias, Universidad Pablo de Olavide de Sevilla, 41013 Sevilla, Spain.
Sáez-Cassanelli
José Luis
JL
Inda
Mari Carmen
MC
de los Santos-Arteaga
Mercedes
M
Sierra-Domínguez
Sergio Antonio
SA
López-Lluch
Guillermo
G
Delgado-García
José María
JM
Carrión
Angel Manuel
AM
D000818:Animals; D031204:Caloric Restriction / Q000379:methods; D003213:Conditioning, Psychological / Q000502:physiology; D007858:Learning / Q000502:physiology*; D008297:Male; D051379:Mice; D009473:Neuronal Plasticity / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D013569:Synapses / Q000235:genetics / Q000378:metabolism*
C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate