Alterations of cAMP response element-binding activity in the aged rat brain in response to administration of rolipram, a cAMP-specific phosphodiesterase inhibitor

Asanuma, Masato; Nishibayashi, Sakiko; Iwata, Emi; Kondo, Yoichi; Nakanishi, Tohru; Vargas, Marvin Gómez; Ogawa, Norio

doi:10.1016/0169-328x(96)00098-8

Cited by 66 publications

(36 citation statements)

References 17 publications

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“…This would increase PKA activity and CREB phosphorylation, potentially reversing the hippocampus-dependent memory and L-LTP defects. Consistent with this idea, administration of rolipram in aged rats was found to reverse an age-related decrease in CREbinding activity (33). In addition, D1/D5 agonists and rolipram might also improve age-related defects in spatial memory by modulating the cholinergic system in the hippocampus (6,(39)(40)(41).…”

Section: Discussionsupporting

confidence: 61%

“…Our studies of L-LTP in vitro demonstrate that the aging defect is intrinsic to the hippocampus itself and does not depend on input from other brain areas. In addition, we used the same experimental protocols as previous pharmacological and genetic studies that have shown that L-LTP in the CA1 region of hippocampus in vitro is mediated in part by D1/D5 receptors, cAMP, PKA activity, CREB phosphorylation, and mRNA and protein synthesis (14)(15)(16)(17)(18)(19)(20)(21)(22) (1999) biochemical evidence that suggests that there are age-related changes in the hippocampus that involve the same dopaminecAMP-PKA-CREB signaling pathway (31)(32)(33). Thus, the poor maintenance of both memory and L-LTP observed in aged mice may reflect alterations in this molecular pathway.…”

Section: Discussionmentioning

confidence: 99%

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Age-related defects in spatial memory are correlated with defects in the late phase of hippocampal long-term potentiation in vitro and are attenuated by drugs that enhance the cAMP signaling pathway

Bach

Barad

Son

et al. 1999

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

522

339

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To study the physiological and molecular mechanisms of age-related memory loss, we assessed spatial memory in C57BL/B6 mice from different age cohorts and then measured in vitro the late phase of hippocampal longterm potentiation (L-LTP). Most young mice acquired the spatial task, whereas only a minority of aged mice did. Aged mice not only made significantly more errors but also exhibited greater individual differences. Slices from the hippocampus of aged mice exhibited significantly reduced L-LTP, and this was significantly and negatively correlated with errors in memory. Because L-LTP depends on cAMP activation, we examined whether drugs that enhanced cAMP would attenuate the L-LTP and memory defects. Both dopamine D1/D5 receptor agonists, which are positively coupled to adenylyl cyclase, and a cAMP phosphodiesterase inhibitor ameliorated the physiological as well as the memory defects, consistent with the idea that a cAMP-protein kinase A-dependent signaling pathway is defective in age-related spatial memory loss.

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Section: Discussionsupporting

confidence: 61%

Section: Discussionmentioning

confidence: 99%

Age-related defects in spatial memory are correlated with defects in the late phase of hippocampal long-term potentiation in vitro and are attenuated by drugs that enhance the cAMP signaling pathway

Bach

Barad

Son

et al. 1999

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

522

339

View full text Add to dashboard Cite

show abstract

“…Preclinical studies conducted to date do support the potential utility of PDE4 inhibitors in the treatment of depressive disorders. Thus, long-term administration of PDE4 inhibitors increases the expression of CREB and BDNF in the hippocampus of rats (Asanuma et al 1996;Fujimaki et al 2000), and PDE inhibitors have antidepressant-like effects in behavioral models (Griebel et al 1991;O'Donnell 1993;Wachtel and Schneider 1986).…”

Section: Strategies To Potentiate the Creb/bdnf/ Bcl-2 Cascade For Thmentioning

confidence: 99%

Enhancing neuronal plasticity and cellular resilience to develop novel, improved therapeutics for Difficult-to-Treat depression

Manji

Quiróz

Sporn

et al. 2003

Biological Psychiatry

445

259

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“…Lund et al 2004). Aged rats display decreased basal forebrain and hippocampus CREB-DNA binding (Asanuma et al 1996). Expression of phosphorylated CREB (pCREB) appears to be reduced in the hippocampus of aged rats (Foster et al 2001;Brightwell et al 2004;Kudo et al 2005; but see also Monti et al 2005).…”

mentioning

confidence: 99%

Rapid forgetting of social transmission of food preferences in aged rats: Relationship to hippocampal CREB activation

Countryman¹,

Gold²

2007

Learn. Mem.

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A major characteristic of age-related changes in memory in rodents is an increase in the rate of forgetting of new information, even when tests given soon after training reveal intact memory. Interference with CREB functions similarly results in rapid decay of memory. Using quantitative immunocytochemistry, the present experiment examined the number of CREB-and pCREB-immunoreactive neurons in three regions of the dorsal and ventral hippocampus (dentate gyrus, CA3, and CA1) as a function of age and training. Rats were trained in a social transmission of food preference task. Using different food pairings, memory was tested in each rat immediately and 1, 2, 3, and 7 d later. Both young and old rats had intact and comparable memory scores at the immediate and 24-h tests, but old rats exhibited more rapid forgetting thereafter relative to that of young rats. The main findings were that training resulted in large increases in the number of pCREB-immunoreactive cells throughout the hippocampus in both young and aged rats. However, particularly in the ventral hippocampus, the training-elicited increase in pCREB-positive neurons was significantly lower in old than in young rats. Based on Western blot analyses in a separate set of rats, CREB levels were not responsive to training but were lower in the ventral hippocampus of old rats than of young rats. The present findings suggest that lower activation of CREB after training may contribute to the rapid forgetting seen in aged rats.Rats and mice exhibit age-related impairments in learning and memory on many tasks. Often, the impairments can be characterized in terms of rapid forgetting, in which aged rats and mice have relatively comparable learning and memory on tests soon after training, but poor memory at later times after training (Barnes and McNaughton 1985;

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Alterations of cAMP response element-binding activity in the aged rat brain in response to administration of rolipram, a cAMP-specific phosphodiesterase inhibitor

Cited by 66 publications

References 17 publications

Age-related defects in spatial memory are correlated with defects in the late phase of hippocampal long-term potentiation in vitro and are attenuated by drugs that enhance the cAMP signaling pathway

Age-related defects in spatial memory are correlated with defects in the late phase of hippocampal long-term potentiation in vitro and are attenuated by drugs that enhance the cAMP signaling pathway

Enhancing neuronal plasticity and cellular resilience to develop novel, improved therapeutics for Difficult-to-Treat depression

Rapid forgetting of social transmission of food preferences in aged rats: Relationship to hippocampal CREB activation

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