Sequential increase in Egr-1 and AP-1 DNA binding activity in the dentate gyrus following the induction of long-term potentiation

Williams, Joanna M.; Beckmann, Alison M.; Mason-Parker, Sara E.; Abraham, Wickliffe C.; Wilce, Peter A.; Tate, Warren P.

doi:10.1016/s0169-328x(00)00061-9

Cited by 43 publications

(32 citation statements)

References 46 publications

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“…For this purpose we examined the colocalization of BrdU incorporation with NeuN, a marker of mature, differentiated neurons, and with the early functional gene Zif268 in the BrdU ϩ cells, as a marker for synaptic functionality in neurons (25,28,65).…”

Section: Methodsmentioning

confidence: 99%

Stimulation of endogenous neurogenesis by anti-EFRH immunization in a transgenic mouse model of Alzheimer's disease

Becker

Lavie²,

Solomon³

2007

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

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Neurogenesis is a subject of intense interest and extensive research, but it stands at the center of a bitter debate over ethical and practical problems. Neurodegenerative diseases, such as Alzheimer's disease (AD), accompanied by a shifting balance between neurogenesis and neurodegeneration, are suitable for stimulation of neurogenesis for the benefit of diseased patients. We have previously shown that Abs against the EFRH sequence of ␤-amyloid peptide (A␤P) prevent aggregation and disaggregate A␤P both in vitro and in vivo. EFRH, located in the soluble tail of the N-terminal region, acts as a regulatory site controlling both solubilization and disaggregation processes in the A␤P molecule. Here we show that anti-EFRH immunotherapy of a platelet-derived amyloid precursor protein transgenic mouse model of AD stimulates endogenous neurogenesis, suggested by elevated numbers of BrdU-incorporated cells, most of which are colocalized with a marker of mature neurons, NeuN. These newly born neurons expressed the activitydependent gene Zif268, indicating their functional integration and participation in response to synaptic input in the brain. These findings suggest that anti-amyloid immunotherapy may promote recovery from AD or other diseases related to A␤P overproduction and neurotoxicity by restoring neuronal population, as well as cognitive functions in treated patients.amyloid ␤ ͉ immunotherapy ͉ neurodegenerative diseases ͉ platelet-derived amyloid precursor protein transgenic mice A dult brain neurogenesis continues throughout life, helping to maintain nervous-system integrity. It involves neural stem cells (NSC) found in the two principal neurogenic regions: the subgranular zone (SGZ) of the dentate gyrus (DG), which generates the hippocampal interneurons (1), and the forebrain subventricular zone (SVZ) of the lateral ventricles, which migrate to the olfactory bulb (2-5). NSC are self-renewing, multipotent cells that generate neurons, astrocytes, and oligodendrocytes in the nervous system. These progenitor cells migrate to their final locations and functions, becoming neurons or glia depending on their microenvironment (reviewed in ref. 6). Alterations in the microenvironment may affect neurogenesis, rendering it ectopic or even blocked, thus leading to deficits in learning and memory (7-9).One of the major pathological features of the Alzheimer's disease (AD) patient's brain tissue is the abundance of amyloid plaques, composed of ␤-amyloid peptide (A␤P) (10). The amyloid cascade hypothesis states that overproduction of A␤P, or failure to clear it, leads to AD primarily through amyloid deposition associated with cell death, which is reflected in memory impairment (11,12).During the last decade, anti-A␤P immunization proved effective in amyloid burden reduction and improvement of memory deficits in AD transgenic (Tg) mice (13,14) and in AD patients (15). A few main mechanisms are considered to be involved in immunotherapy efficacy: catalytic dissolution of A␤ fibrils (16); opsonization of amyloid by the Ab and su...

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Section: Methodsmentioning

confidence: 99%

Stimulation of endogenous neurogenesis by anti-EFRH immunization in a transgenic mouse model of Alzheimer's disease

Becker

Lavie²,

Solomon³

2007

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

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“…Once stimulated, zif268 protein binds to its response element, and this binding has been detected after induction of LTP (644). Interestingly, it has become clear that LTP, induced in adult visual cortex by stimulation of the lateral geniculate nucleus (229) and in insular cortex by stimulation of the basolateral amygdala (266), is associated with an increase in zif268 immunoreactivity, although there is no evidence of a similar response in CA1 after stimulation of Schaffer collaterals (166).…”

Section: E Activation Of Iegs and Late-response Genes In Ltpmentioning

confidence: 99%

Long-Term Potentiation and Memory

Lynch

2004

Physiological Reviews

1,684

1,098

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Lynch, MA. Long-Term Potentiation and Memory. Physiol Rev 84: 87–136, 2004; 10.1152/physrev.00014.2003.—One of the most significant challenges in neuroscience is to identify the cellular and molecular processes that underlie learning and memory formation. The past decade has seen remarkable progress in understanding changes that accompany certain forms of acquisition and recall, particularly those forms which require activation of afferent pathways in the hippocampus. This progress can be attributed to a number of factors including well-characterized animal models, well-defined probes for analysis of cell signaling events and changes in gene transcription, and technology which has allowed gene knockout and overexpression in cells and animals. Of the several animal models used in identifying the changes which accompany plasticity in synaptic connections, long-term potentiation (LTP) has received most attention, and although it is not yet clear whether the changes that underlie maintenance of LTP also underlie memory consolidation, significant advances have been made in understanding cell signaling events that contribute to this form of synaptic plasticity. In this review, emphasis is focused on analysis of changes that occur after learning, especially spatial learning, and LTP and the value of assessing these changes in parallel is discussed. The effect of different stressors on spatial learning/memory and LTP is emphasized, and the review concludes with a brief analysis of the contribution of studies, in which transgenic animals were used, to the literature on memory/learning and LTP.

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“…In addition to the expression of Zif268, other members of the Erg family, such as Krox-20 and Egr-3, are also upregulated after LTP in the dentate gyrus (Yamagata et al, 1994;Williams et al, 1995). Recently, analysis of Zif268 DNA binding activity using gel-shift assays showed that the increase in Zif268 protein after induction of LTP is associated with increased binding of the protein to its response element (Williams et al, 2000). The expression of Zif268 is also upregulated in the insular cortex after LTP-inducing stimulation of afferents from the basolateral amygdala (Jones et al, 1999), suggesting a role for Zif268 in activity-dependent neuronal function in other brain regions.…”

Section: Regulated Transcription Of Zif268 In Synaptic Plasticity Andmentioning

confidence: 99%

Regulated transcription of the immediate‐early gene Zif268: Mechanisms and gene dosage‐dependent function in synaptic plasticity and memory formation

2002

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ABSTRACT:The immediate-early gene Zif268 is a member of the Egr family of inducible transcription factors. Data from gene expression studies have suggested that this gene may play a critical role in initial triggering of the genetic machinery that has long been considered a necessary mechanism for maintenance of the later phases of LTP and also for the consolidation or stabilization of long-lasting memories. Until recently, however, the data supporting this assumption have been based primarily on circumstantial evidence, with no direct evidence to suggest that Zif268 is required for long-lasting synaptic plasticity and memory. In this report, we review our own data using Zif268 mutant mice; we show that although the early phase of dentate gyrus LTP is normal in these mice, the later phases are not present, and the ability of the mice to maintain learned information over a 24-h period is deficient. In addition, we present new information showing a task-dependent gene dosage effect in Zif268 heterozygous mice. We show that spatial learning is particularly sensitive to reduced levels of Zif268, as one-half of the complement of Zif268 in heterozygous mice is insufficient to maintain spatial long-term memories.

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Sequential increase in Egr-1 and AP-1 DNA binding activity in the dentate gyrus following the induction of long-term potentiation

Cited by 43 publications

References 46 publications

Stimulation of endogenous neurogenesis by anti-EFRH immunization in a transgenic mouse model of Alzheimer's disease

Stimulation of endogenous neurogenesis by anti-EFRH immunization in a transgenic mouse model of Alzheimer's disease

Long-Term Potentiation and Memory

Regulated transcription of the immediate‐early gene Zif268: Mechanisms and gene dosage‐dependent function in synaptic plasticity and memory formation

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