Alteration of CREB phosphorylation and spatial memory deficits in aged 129T2/Sv mice

Porte, Yves; Buhot, Marie-Christine; Mons, Nicole

doi:10.1016/j.neurobiolaging.2007.03.023

Cited by 70 publications

(54 citation statements)

References 77 publications

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“…CREB phosphorylation is considered a molecular marker of memory processing for spatial learning in the hippocampus (Mizuno et al, 2002;Colombo et al, 2003;Porte et al, 2008). CREB-dependent upregulation of GRIN2B and kif17 gene transcription has also been reported (Wong et al, 2002;Yin et al, 2011).…”

Section: Creb Phosphorylationmentioning

confidence: 97%

Regulation of NMDA Receptor Transport: A KIF17–Cargo Binding/Releasing Underlies Synaptic Plasticity and MemoryIn Vivo

et al. 2012

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Regulation of NMDA receptor trafficking is crucial to modulate neuronal communication. Ca 2ϩ/calmodulin-dependent protein kinase phosphorylates the tail domain of KIF17, a member of the kinesin superfamily, to control NMDA receptor subunit 2B (GluN2B) transport by changing the KIF17-cargo interaction in vitro. However, the mechanisms of regulation of GluN2B transport in vivo and its physiological significance are unknown. We generated transgenic mice carrying wild-type KIF17 (TgS), or KIF17 with S1029A (TgA) or S1029D (TgD) phosphomimic mutations in kif17 Ϫ / Ϫ background. TgA/kif17 Ϫ / Ϫ and TgD/kif17 Ϫ / Ϫ mice exhibited reductions in synaptic NMDA receptors because of their inability to load/unload GluN2B onto/from KIF17, leading to impaired neuronal plasticity, CREB activation, and spatial memory. Expression of GFP-KIF17 in TgS/kif17 Ϫ / Ϫ mouse neurons rescued the synaptic and behavioral defects of kif17 Ϫ / Ϫ mice. These results suggest that phosphorylation-based regulation of NMDA receptor transport is critical for learning and memory in vivo.

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Section: Creb Phosphorylationmentioning

confidence: 97%

Regulation of NMDA Receptor Transport: A KIF17–Cargo Binding/Releasing Underlies Synaptic Plasticity and MemoryIn Vivo

et al. 2012

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“…Generally, decreased CREB activity was associated with learning impairments in healthy aged animals [31,32] and with cognitive deficits in animal models of neurodegenerative disorders [33][34][35]. Importantly, the level of phosphorylated CREB and the activity-induced increase in CREB phosphorylation is diminished in ageing [36,37], and this itself may influence the ageing process [38,39]. Altered calcium signalling in ageing neurons significantly contributes to diminished CREB activity.…”

Section: Functional Histological and Molecular Changes In The Ageingmentioning

confidence: 99%

The endocannabinoid system in normal and pathological brain ageing

Bilkei-Gorzó

2012

Phil. Trans. R. Soc. B

116

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The role of endocannabinoids as inhibitory retrograde transmitters is now widely known and intensively studied. However, endocannabinoids also influence neuronal activity by exerting neuroprotective effects and regulating glial responses. This review centres around this less-studied area, focusing on the cellular and molecular mechanisms underlying the protective effect of the cannabinoid system in brain ageing. The progression of ageing is largely determined by the balance between detrimental, proageing, largely stochastic processes, and the activity of the homeostatic defence system. Experimental evidence suggests that the cannabinoid system is part of the latter system. Cannabinoids as regulators of mitochondrial activity, as anti-oxidants and as modulators of clearance processes protect neurons on the molecular level. On the cellular level, the cannabinoid system regulates the expression of brainderived neurotrophic factor and neurogenesis. Neuroinflammatory processes contributing to the progression of normal brain ageing and to the pathogenesis of neurodegenerative diseases are suppressed by cannabinoids, suggesting that they may also influence the ageing process on the system level. In good agreement with the hypothesized beneficial role of cannabinoid system activity against brain ageing, it was shown that animals lacking CB1 receptors show early onset of learning deficits associated with age-related histological and molecular changes. In preclinical models of neurodegenerative disorders, cannabinoids show beneficial effects, but the clinical evidence regarding their efficacy as therapeutic tools is either inconclusive or still missing.

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“…We and others have previously reported that acquisition of spatial learning was associated with a progressive increase in CREB phosphorylation in the hippocampus without changes in total CREB protein (Mizuno et al 2002;Colombo et al 2003;Porte et al 2008). We first used immunohistochemistry to investigate whether acquisition of the Ref-4T task induced learning-specific, time-dependent changes in the number of pCREB immunoreactive (pCREB-ir) nuclei in the dorsal hippocampus (both CA1-CA3 areas).…”

Section: Acquisition Of the Spatial Reference Memory Task Is Associatmentioning

confidence: 99%

“…Acquisition of the reference memory requires the hippocampus to form spatial associations between the PF location and the surrounding environment, making the hippocampus necessary for this task (Morris et al 1982;Sutherland et Acquisition of the spatial reference task was associated with region-specific patterns of CREB phosphorylation A post-training phosphorylation of CREB has been implicated in memory formation of spatial learning tasks in rodents (Mizuno et al 2002;Colombo et al 2003;Martel et al 2007;Porte et al 2008). Our results show that acquisition of the reference memory task is associated with significant changes in pCREB levels which varied as a function of both the regions considered and the degree of learning.…”

Section: Behaviormentioning

confidence: 99%

Spatial memory in the Morris water maze and activation of cyclic AMP response element-binding (CREB) protein within the mouse hippocampus

Porte¹,

Buhot²,

Mons³

2008

Learn. Mem.

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We investigated the spatio-temporal dynamics of learning-induced cAMP response element-binding protein activation/phosphorylation (pCREB) in mice trained in a spatial reference memory task in the water maze. Using immunohistochemistry, we examined pCREB immunoreactivity (pCREB-ir) in hippocampal CA1 and CA3 and related brain structures. During the course of spatial learning over Days 1-9, pCREB-ir progressively increased in hippocampal neurons whereas its level in the dorsal striatum decreased. No significant changes were observed in the prelimbic cortex and lateral amygdala. Mice killed at various time points after the last training session demonstrated two waves of pCREB-ir in CA1 and an early transient CREB phosphorylation in area CA3, lateral amygdala, and prelimbic cortex. We show that CREB phosphorylation and downstream gene Zif268 activation remained sustained in CA1 and CA3 for at least 24 h after extended training (Days 8-9) but not during early training (Day 3). The present results indicate that the strong CA1 CREB phosphorylation observed immediately after training was not related strictly to learning or to memory. In contrast, at 15 min after training, the changes in CA1 CREB phosphorylation state were specifically related to individual learning capability. We suggest that hippocampal-learning specificity of CREB is reflected best by duration, rather than magnitude, of CREB phosphorylation.Memory can be divided into at least two distinct forms according to its temporal and biochemical properties: short term memory (STM), which lasts no longer than a few hours, and long-term memory (LTM), which lasts from several hours to days or even longer (McGaugh 1966;Davis and Squire 1984;Matthies 1989; Bozon et al. 2003a,b). Studies in rodents have provided evidence that STM is a labile state that depends on activation and/or posttranslational modifications of preexisting molecules whereas consolidation of LTM depends on a crucial phase of gene expression and de novo protein synthesis to transform newly learned information into a permanent and stable state (Davis and Squire 1984;Dudai 1996;McGaugh 2000). Numerous studies have shown that consolidation of many types of LTM in rodents requires phosphorylation/activation of the transcription factor CREB (cAMP response element-binding protein) on Ser 133 by cAMP-or Ca 2+ -dependent protein kinase (Bernabeu et al. 1997;Izquierdo and Medina 1997;Impey et al. 1998;Taubenfeld et al. 1999;Cammarota et al. 2000Cammarota et al. , 2005Vianna et al. 2000;Izquierdo et al. 2001;Stanciu et al. 2001;Kida et al. 2002;Desmedt et al. 2003;Zhang et al. 2003;Countryman et al. 2005;Trifilieff et al. 2006;Brightwell et al. 2007). We and others recently showed that spatial memory formation was associated with increased CREB phosphorylation within the hippocampus (Mizuno et al. 2002;Colombo et al. 2003;Goldbart et al. 2003;Martel et al. 2006;Moncada and Viola 2006; Porte et al.2008). Indeed, a role for CREB in hippocampus-dependent learning was strongly supported by oligonucleotide antis...

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Alteration of CREB phosphorylation and spatial memory deficits in aged 129T2/Sv mice

Cited by 70 publications

References 77 publications

Regulation of NMDA Receptor Transport: A KIF17–Cargo Binding/Releasing Underlies Synaptic Plasticity and MemoryIn Vivo

Regulation of NMDA Receptor Transport: A KIF17–Cargo Binding/Releasing Underlies Synaptic Plasticity and MemoryIn Vivo

The endocannabinoid system in normal and pathological brain ageing

Spatial memory in the Morris water maze and activation of cyclic AMP response element-binding (CREB) protein within the mouse hippocampus

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