Immediate-early genes, neuronal plasticity, and memory

Ha, Robertson

doi:10.1139/o92-112

Cited by 104 publications

(37 citation statements)

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“…c-fos is one of the immediate-early genes induced by neural activity and behavioral training and a marker for the activated neurons (34)(35)(36)(37). Immediate-early gene expression plays a functional role in the neuroplastic mechanisms required for the memory consolidation processes (38,39). To address if enhanced neurogenesis by FGF2 expression is associated with neural activation, c-fos-immunoreactive (c-fos + ) neurons were evaluated in the granular cell layer of the dentate gyrus in this study (Fig.…”

Section: Fgf2 Gene Expression Increases Neuronal C-fos Expression In Thementioning

confidence: 99%

FGF2 gene transfer restores hippocampal functions in mouse models of Alzheimer's disease and has therapeutic implications for neurocognitive disorders

Kiyota

Ingraham

Jacobsen

et al. 2011

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

121

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The adult hippocampus plays a central role in memory formation, synaptic plasticity, and neurogenesis. The subgranular zone of the dentate gyrus contains neural progenitor cells with self-renewal and multilineage potency. Transgene expression of familial Alzheimer's disease-linked mutants of β-amyloid precursor protein (APP) and presenilin-1 leads to a significant inhibition of neurogenesis, which is potentially linked to age-dependent memory loss. To investigate the effect of neurogenesis on cognitive function in a relevant disease model, FGF2 gene is delivered bilaterally to the hippocampi of APP+presenilin-1 bigenic mice via an adenoassociated virus serotype 2/1 hybrid (AAV2/1-FGF2). Animals injected with AAV2/1-FGF2 at a pre- or postsymptomatic stage show significantly improved spatial learning in the radial arm water maze test. A neuropathological investigation demonstrates that AAV2/1-FGF2 injection enhances the number of doublecortin, BrdU/NeuN, and c-fos–positive cells in the dentate gyrus, and the clearance of fibrillar amyloid-β peptide (Aβ) in the hippocampus. AAV2/1-FGF2 injection also enhances long-term potentiation in another APP mouse model (J20) compared with control AAV2/1-GFP–injected littermates. An in vitro study confirmed the enhanced neurogenesis of mouse neural stem cells by direct AAV2/1-FGF2 infection in an Aβ oligomer-sensitive manner. Further, FGF2 enhances Aβ phagocytosis in primary cultured microglia, and reduces Aβ production from primary cultured neurons after AAV2/1-FGF2 infection. Thus, our data indicate that virus-mediated FGF2 gene delivery has potential as an alternative therapy of Alzheimer's disease and possibly other neurocognitive disorders.

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Section: Fgf2 Gene Expression Increases Neuronal C-fos Expression In Thementioning

confidence: 99%

FGF2 gene transfer restores hippocampal functions in mouse models of Alzheimer's disease and has therapeutic implications for neurocognitive disorders

Kiyota

Ingraham

Jacobsen

et al. 2011

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

121

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“…When birds sing, mRNA synthesis of some of these same genes is increased in subsets of structures of the vocal pathway (Jarvis and Nottebohm 1997;Kimbo and Doupe 1997;Li et al 2000;Li and Jarvis 2001). The first three genes are transcription factors; they regulate expression of specific target genes (Robertson 1992;Herdegen and Leah 1998). The latter, BDNF, is a trophic factor and is released from cells to bind to receptors that lead to changes in cell signaling, gene expression, and cell survival (Altar et al 1997).…”

Section: Molecularmentioning

confidence: 99%

A framework for integrating the songbird brain

Jarvis

Smith

Wada

et al. 2002

Journal of Comparative Physiology A: Sensory, Neural, and Behav

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Biological systems by default involve complex components with complex relationships. To decipher how biological systems work, we assume that one needs to integrate information over multiple levels of complexity. The songbird vocal communication system is ideal for such integration due to many years of ethological investigation and a discreet dedicated brain network. Here we announce the beginnings of a songbird brain integrative project that involves high-throughput, molecular, anatomical, electrophysiological and behavioral levels of analysis. We first formed a rationale for inclusion of specific biological levels of analysis, then developed high-throughput molecular technologies on songbird brains, developed technologies for combined analysis of electrophysiological activity and gene regulation in awake behaving animals, and developed bioinformatic tools that predict causal interactions within and between biological levels of organization. This integrative brain project is fitting for the interdisciplinary approaches taken in the current songbird issue of the Journal of Comparative Physiology A and is expected to be conducive to deciphering how brains generate and perceive complex behaviors.

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“…Inducible immediate-early genes (IEGs), or genes which respond rapidly and transiently to a variety of stimuli (Robertson, 1992), may serve as markers of neuronal activity and thereby aid in our understanding of the neural basis of behavior. Of these IEGs, neuroscientists have paid particular attention to c-fos gene expression (Sheng and Greenberg, 1990).…”

Section: Introductionmentioning

confidence: 99%

Restraint-induced fra-2 and c-fos expression in the rat forebrain: Relationship to stress duration

2007

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The protein product of the fra-2 gene (Fra-2), a fos-family member, can compete with Fos protein for participation in AP-1 transcription factor complexes and each protein can contribute different transactivational consequences to an AP-1 complex. To date, there is limited characterization of fra-2 mRNA expression in the rat forebrain. We examined basal and restraint-induced mRNA expression (in situ hybridization) of fra-2 in the rat forebrain and compared its temporal-spatial pattern to c-fos. In contrast to the very low basal expression of c-fos, fra-2 basal expression was moderately high throughout cortex and some subcortical structures, including prominent basal expression in the hypothalamic paraventricular nucleus (PVN). Restraint-induced fra-2 expression was quantified in the prefrontal cortex (PFC), lateral septum (LS) and PVN. Maximal fra-2 gene induction in the PFC and LS was delayed (60 min) after restraint onset with respect to c-fos (15 min), whereas in the PVN, fra-2 mRNA increased within 15 min of restraint. Additionally we compared c-fos and fra-2 gene expression in rats given shorter or longer restraint durations, but equal total time from stress onset to sample collection, to determine the extent to which the kinetics of gene induction matched that of a hypothalamic-pituitary-adrenal axis hormone response. Rats given 45 min recovery after 15 min restraint showed less c-fos expression in the PVN, less fra-2 expression in the prelimbic and infralimbic PFC, and no difference in the LS compared with rats restrained for 60 min. Thus, the expression of both genes was sensitive to stressor duration, but this sensitivity varied with brain region. Differential basal and stress-induced expression patterns of the fra-2 and c-fos genes are likely to have important functional consequences for AP-1 transcription factor dependent regulation of neural plasticity.

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Immediate-early genes, neuronal plasticity, and memory

Cited by 104 publications

References 0 publications

FGF2 gene transfer restores hippocampal functions in mouse models of Alzheimer's disease and has therapeutic implications for neurocognitive disorders

FGF2 gene transfer restores hippocampal functions in mouse models of Alzheimer's disease and has therapeutic implications for neurocognitive disorders

A framework for integrating the songbird brain

Restraint-induced fra-2 and c-fos expression in the rat forebrain: Relationship to stress duration

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