Age and insulin-like growth factor-1 modulate N-methyl-D-aspartate receptor subtype expression in rats

Sonntag, William E.; Bennett, Scott; Khan, Amir S.; Thornton, Phillip L.; Xu, Xingqi; Ingram, Rhonda L.; Brunso‐Bechtold, Judy K.

doi:10.1016/s0361-9230(99)00259-2

Cited by 127 publications

(103 citation statements)

References 47 publications

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“…1), but the NR2B͞NR2A ratio remained unaffected. The significance of the observed enhancement in NR2A in elderly rats is not clear; however, an age-related increase in the NR2A subunit protein, at least from 10 to 21 months of age, has been reported by others (33). In the same study, the authors demonstrated that intracerebroventricular infusion of IGF-1, a target for GHR-mediated action, can increase NR2A and NR2B subunit proteins in hippocampus of 30-month-old rats.…”

Section: Discussionmentioning

confidence: 63%

“…However, GH responses in the brain may also be mediated by a coordinated effect of both GH and IGF-1. As mentioned above IGF-1, given by intracerebroventricular infusion, is shown to increase the NR2A and NR2B receptor protein in the hippocampus (33). Also, some defects seen with aging are caused by a coordinated loss of the GH͞IGF-1 function (7, 8, Fig.…”

Section: Discussionmentioning

confidence: 83%

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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: Discussionmentioning

confidence: 63%

Section: Discussionmentioning

confidence: 83%

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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“…Both DNA damage and aging result in a reduction of the somatotroph axis by downregulating growth hormone (GH)/IGF1 signaling van de Ven et al, 2006;van der Pluijm et al, 2007;Garinis et al, 2009), which appears to operate in a cell autonomous way, presumably via DNA damage-induced stalling of RNA polymerase II (Garinis et al, 2009). It has been shown that IGF1 regulates synaptic plasticity in the adult CNS (Torres-Aleman, 1999;Sonntag et al, 2000) and that age-related behavioral impairments can be alleviated by IGF1 (Markowska et al, 1998;Shi et al, 2005), thereby suggesting that IGF1 reduction could be a factor in agerelated reduction of synaptic plasticity. In addition, it has recently been shown that the related family member IGF2 facilitates the sta- f/Ϫ mice show impaired fear conditioning and impaired water maze performance at 6 months of age.…”

Section: Discussionmentioning

confidence: 99%

Accelerated Age-Related Cognitive Decline and Neurodegeneration, Caused by Deficient DNA Repair

Borgesius

Waard²,

Pluijm³

et al. 2011

J. Neurosci.

109

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Age-related cognitive decline and neurodegenerative diseases are a growing challenge for our societies with their aging populations. Accumulation of DNA damage has been proposed to contribute to these impairments, but direct proof that DNA damage results in impaired neuronal plasticity and memory is lacking. Here we take advantage of Ercc1 ⌬/Ϫ mutant mice, which are impaired in DNA nucleotide excision repair, interstrand crosslink repair, and double-strand break repair. We show that these mice exhibit an agedependent decrease in neuronal plasticity and progressive neuronal pathology, suggestive of neurodegenerative processes. A similar phenotype is observed in mice where the mutation is restricted to excitatory forebrain neurons. Moreover, these neuron-specific mutants develop a learning impairment. Together, these results suggest a causal relationship between unrepaired, accumulating DNA damage, and age-dependent cognitive decline and neurodegeneration. Hence, accumulated DNA damage could therefore be an important factor in the onset and progression of age-related cognitive decline and neurodegenerative diseases.

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“…In this regard, although we cannot yet establish a mechanistic link between acute and long-term actions of IGF-I on glutamatergic transmission, it is tempting to relate its reported acute effects on glutamate receptor function [39][40][41][42][43][44][45] or in intraneuronal Ca 2 þ mobilization [46][47][48] to long-term increases produced by IGF-I on glutamatergic receptor levels. 49,50 At any rate, since pulse-paired facilitation was not modified in LID hippocampal slices, presynaptic alterations may be ruled out, leaving postsynaptic actions of IGF-I as the most likely mechanism involved in its trophic action on glutamatergic transmission.…”

Section: Discussionmentioning

confidence: 99%

Central actions of liver-derived insulin-like growth factor I underlying its pro-cognitive effects

et al. 2007

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Age and insulin-like growth factor-1 modulate N-methyl-D-aspartate receptor subtype expression in rats

Cited by 127 publications

References 47 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

Accelerated Age-Related Cognitive Decline and Neurodegeneration, Caused by Deficient DNA Repair

Central actions of liver-derived insulin-like growth factor I underlying its pro-cognitive effects

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