Caloric restriction prevents age-related deficits in LTP and in NMDA receptor expression

Eckles-Smith, Karen; Clayton, Daniel A.; Bickford, Paula C.; Browning, Michael

doi:10.1016/s0169-328x(00)00088-7

Cited by 173 publications

(127 citation statements)

References 37 publications

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“…1) is in agreement with a recent observation based on quantitative Western blot analysis (34). However, only a slight, nonsignificant, age-related decrease was observed for the NR1 message, as assessed by kinetic reverse transcription-PCR technique.…”

Section: Discussionsupporting

confidence: 92%

Growth hormone induces age-dependent alteration in the expression of hippocampal growth hormone receptor and N -methyl- d -aspartate receptor subunits gene transcripts in male rats

Grevès

Steensland²,

Grevès³

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

111

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Studies were conducted to evaluate the effects of s.c. injected recombinant human growth hormone (GH) on the expression of the gene transcript of N-methyl-D-aspartate receptor subunits type 1 (NR1), type 2A (NR2A), and type 2B (NR2B) in the male rat hippocampus. The GH-induced effects on the expression of hippocampal gene transcripts of GH receptor (GHR) and GH-binding protein were also examined. Male Sprague-Dawley rats, kept in four groups of two different ages, was treated with the hormone or saline during 10 days before decapitation and tissue dissection. Brain tissues collected were analyzed for mRNA content by using the Northern blot technique. The results indicated that in adult young rats (11 weeks of age) the hormone elicited a decrease in the mRNA expression of NR1 but an increase in that of the NR2B subunit. In elderly adult rats (57-67 weeks of age) GH induced an increase in the expression of the hippocampal message for NR1 and NR2A. Meanwhile, the hormone induced a significant up-regulation of the GHR transcript in hippocampus of adult young rats but not in elderly adult rats. It was further found that a significant positive correlation exists between the level of GHR mRNA and the expression of the NR2B subunit transcript in adult young rats. The GH-induced increase in the expression of hippocampal mRNA for the NR2B subunit is compatible with a previously observed memory promoting effect seen for the hormone, because overexpression of this N-methyl-D-aspartate receptor subunit is shown to enhance cognitive capabilities.

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Section: Discussionsupporting

confidence: 92%

Growth hormone induces age-dependent alteration in the expression of hippocampal growth hormone receptor and N -methyl- d -aspartate receptor subunits gene transcripts in male rats

Grevès

Steensland²,

Grevès³

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

111

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“…We found that both baseline CA3-CA1 synaptic transmission and NMDA receptor-mediated responses were blunted in aged rats, as reported previously (Landfield et al, 1986;Deupree et al, 1993;Barnes et al, 1997;Norris et al, 1998b;Eckles-Smith et al, 2000). However, neither measure differed between AU and AI subjects.…”

Section: Discussionsupporting

confidence: 89%

Theta-Frequency Synaptic Potentiation in CA1In VitroDistinguishes Cognitively Impaired from Unimpaired Aged Fischer 344 Rats

et al. 2002

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Hippocampal-dependent learning and memory deficits have been well documented in aging rodents. The results of several recent studies have suggested that these deficits arise from weakened synaptic plasticity within the hippocampus. In the present study, we examined the relationship between hippocampal long-term potentiation (LTP) in vitro and spatial learning in aged (24-26 months) Fischer 344 rats. We found that LTP induced in the CA1 region using theta-frequency stimulation (5 Hz) is selectively impaired in slices from a subpopulation of aged rats that had shown poor spatial learning in the Morris water maze. LTP at 5 Hz in aged rats that did not show learning deficits was similar to that seen in young (4-6 months) controls. We also found that 5 Hz LTP amplitude strongly correlated with individual learning performance among aged rats. The difference in 5 Hz LTP magnitude among aged rats was not attributable to an altered response to 5 Hz stimulation or to differences in the NMDA receptormediated field EPSP. In addition, no performance-related differences in LTP were seen when LTP was induced with 30 or 70 Hz stimulation protocols. Finally, both 5 Hz LTP and spatial learning in learning-impaired rats were enhanced with the selective muscarinic M 2 antagonist ]benzodiazepin-6-one). These findings reinforce the idea that distinct types of hippocampal LTP offer mechanistic insight into age-associated cognitive decline.

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“…All error bars indicate SEM. oxidative stress pathway (26), caloric restriction pathway (27), and PKA-cAMP pathway (28)(29)(30) by using principally pharmacological approaches. Our approach used "thermogenetics" delimited to a single neuron in the fly brain.…”

Section: Discussionmentioning

confidence: 99%

Aging impairs intermediate-term behavioral memory by disrupting the dorsal paired medial neuron memory trace

Tonoki

Davis

2012

Proc. Natl. Acad. Sci. U.S.A.

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How the functional activity of the brain is altered during aging to cause age-related memory impairments is unknown. We used functional cellular imaging to monitor two different calcium-based memory traces that underlie olfactory classical conditioning in young and aged Drosophila. Functional imaging of neural activity in the processes of the dorsal paired medial (DPM) and mushroom body neurons revealed that the capacity to form an intermediateterm memory (ITM) trace in the DPM neurons after learning is lost with age, whereas the capacity to form a short-term memory trace in the α′/β′ mushroom body neurons remains unaffected by age. Stimulation of the DPM neurons by activation of a temperaturesensitive cation channel between acquisition and retrieval enhanced ITM in aged but not young flies. These data indicate that the functional state of the DPM neurons is selectively altered with age to cause an age-related impairment of ITM, and demonstrate that altering the excitability of DPM neurons can restore age-related memory impairments.

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Caloric restriction prevents age-related deficits in LTP and in NMDA receptor expression

Cited by 173 publications

References 37 publications

Growth hormone induces age-dependent alteration in the expression of hippocampal growth hormone receptor and N -methyl- d -aspartate receptor subunits gene transcripts in male rats

Growth hormone induces age-dependent alteration in the expression of hippocampal growth hormone receptor and N -methyl- d -aspartate receptor subunits gene transcripts in male rats

Theta-Frequency Synaptic Potentiation in CA1In VitroDistinguishes Cognitively Impaired from Unimpaired Aged Fischer 344 Rats

Aging impairs intermediate-term behavioral memory by disrupting the dorsal paired medial neuron memory trace

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