Long-term potentiation and synaptic protein phosphorylation

Pasinelli, Piera; Ramakers, G.J.A.; Urban, I.J.A.; Hens, Jacques J. H.; Oestreicher, A.B.; Graan, P.N.E. de; Gispen, Willem Hendrik

doi:10.1016/0166-4328(94)00124-x

Cited by 72 publications

(43 citation statements)

References 59 publications

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“…Cold Spring Harbor Laboratory Press on April 28, 2019 -Published by learnmem.cshlp.org Downloaded from that increased activation of PKC following induction of LTP has been reported (Akers et al 1986;Angenstein et al 1994;Pasinelli et al 1995), as well as an increase in presynaptic PKC activity in area CA1 (Leahy et al 1993). Although indirect, the parallel responses in PKC activity following a learning paradigm and induction of LTP, provide further support for the notion that LTP is a biological substrate for learning and/or memory.…”

Section: Discussionmentioning

confidence: 65%

Training in the Morris water maze occludes the synergism between ACPD and arachidonic acid on glutamate release in synaptosomes prepared from rat hippocampus.

McGahon¹,

Hölscher²,

McGlinchey³

et al. 1996

Learn. Mem.

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In~oducUonWe report here that release of glutamate, inositol phospholipid metabolism, and protein kinase C (PKC) activity are increased in synaptosomes prepared from hippocampi of rats that had been trained in a spatial learning task. In hippocampi obtained from animals that were untrained, activation of the metabotropic glutamate receptor by the specific agonist trans, l.amino.cyclopentyl, l ,3.dicarboxylate (ACPD) increased release of glutamate but only in the presence of a low concentration of arachidonic acid. A similar interaction between arachidonic acid and ACPD was observed on inositol phospholipid turnover and on PKC activity. However, the synergistic effect of arachidonic acid and ACPD on glutamate release was occluded in hippocampal synaptosomes prepared from trained rats. Occlusion of the effect on inositol phospholipid turnover and PKC activation was also observed. These data suggest that the molecular changes that underlie spatial learning may include activation of metabotropic glutamate receptors in the presence of arachidonic acid and that the interaction between arachidonic acid and ACPD triggers the presynaptic changes that accompany learning.3Corresponding author.

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Section: Discussionmentioning

confidence: 65%

Training in the Morris water maze occludes the synergism between ACPD and arachidonic acid on glutamate release in synaptosomes prepared from rat hippocampus.

McGahon¹,

Hölscher²,

McGlinchey³

et al. 1996

Learn. Mem.

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“…Expression of cAMP-dependent protein kinase C ␤ also decreased more than 3-fold in both the aged hypothalamus and cortex. This protein kinase plays an important role in synaptic plasticity and memory formation (17,18), suggesting that down-regulation of the kinase may directly contribute to age-related memory deficits.…”

Section: Resultsmentioning

confidence: 99%

The effects of aging on gene expression in the hypothalamus and cortex of mice

Jiang

Tsien

Schultz

et al. 2001

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

298

191

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A better understanding of the molecular effects of aging in the brain may help to reveal important aspects of organismal aging, as well as processes that lead to age-related brain dysfunction. In this study, we have examined differences in gene expression in the hypothalamus and cortex of young and aged mice by using high-density oligonucleotide arrays. A number of key genes involved in neuronal structure and signaling are differentially expressed in both the aged hypothalamus and cortex, including synaptotagmin I, cAMP-dependent protein kinase C ␤, apolipoprotein E, protein phosphatase 2A, and prostaglandin D. Misregulation of these proteins may contribute to age-related memory deficits and neurodegenerative diseases. In addition, many proteases that play essential roles in regulating neuropeptide metabolism, amyloid precursor protein processing, and neuronal apoptosis are up-regulated in the aged brain and likely contribute significantly to brain aging. Finally, a subset of these genes whose expression is affected by aging are oppositely affected by exposure of mice to an enriched environment, suggesting that these genes may play important roles in learning and memory.A lthough the molecular basis of aging remains unknown, a large body of evidence indicates that oxidative stress results in DNA damage that subsequently leads to changes in gene expression and organismal aging (1). Genetic modifications or spontaneous mutations in a variety of organisms that result in oxidative stress resistance increase longevity (2-4). In Caenorhabditis elegans, the reduction of metabolic rate through genetic manipulation or environmental changes increases life span (5). Dietary restriction also delays the aging process and extends life span (1), possibly by lowering metabolic rate and thus reducing the production of reactive oxygen species.The hypothalamus plays a key role in regulating metabolism. Consequently, an understanding of the effects of aging on the hypothalamus may provide important insights into the organismal aging process. For example, it has been shown that neuroendocrine regulation of insulin signaling affects longevity in C. elegans (6-8). In mammals, hypothalamic modulation of the neuroendocrine system may regulate the aging process by controlling the production, processing, and degradation of neuroendocrine hormones and neuropeptides.To better understand the molecular processes involved in aging, we have examined changes in gene expression in the aged hypothalamus. To determine whether these age-associated gene expression changes are tissue specific, we also analyzed gene expression in the cortex of young and aged mice. Our results demonstrate that the expression levels of many genes related to neuronal signaling, plasticity, and structure were changed in the aged brain. Moreover, many proteases were up-regulated during the aging process in both hypothalamus and cortex, a number of which are involved in the processing and degradation of neuropeptides. Altered expression of these genes may contribute to age-r...

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“…These transcripts are predominantly expressed in the cerebellum of animals up to the age of ϳ3 weeks. Interestingly, these inserts change the charge to the molecule and introduce additional potential phosphorylation sites for protein kinase C, an enzyme that is known to be involved in the regulation of synaptic assembly and plasticity (Shearman et al, 1991;Ben-Ari et al, 1992;Wang and Feng, 1992;Abeliovich et al, 1993;K lann et al, 1993;Moriya and Tanaka, 1994;Reymann and Staak, 1994;Pasinelli et al, 1995). Further studies must clarify whether these developmentally regulated processing variants are involved in early synaptogenesis and /or growth cone regulation.…”

Section: Prosap1 Isoforms May Be Functionally Involved In the Assemblmentioning

confidence: 99%

Proline-Rich Synapse-Associated Protein-1/Cortactin Binding Protein 1 (ProSAP1/CortBP1) Is a PDZ-Domain Protein Highly Enriched in the Postsynaptic Density

Boeckers

Kreutz

Winter³

et al. 1999

J. Neurosci.

222

112

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The postsynaptic density (PSD) is crucially involved in the structural and functional organization of the postsynaptic neurotransmitter reception apparatus. Using antisera against rat brain synaptic junctional protein preparations, we isolated cDNAs coding for proline-rich synapse-associated protein-1 (ProSAP1), a PDZ-domain protein. This protein was found to be identical to the recently described cortactin-binding protein-1 (CortBP1). Homology screening identified a related protein, ProSAP2. Specific antisera raised against a C-terminal fusion construct and a central part of ProSAP1 detect a cluster of immunoreactive bands of 180 kDa in the particulate fraction of rat brain homogenates that copurify with the PSD fraction. Transcripts and immunoreactivity are widely distributed in the brain and are upregulated during the period of synapse formation in the brain. In addition, two short N-terminal insertions are detected; they are differentially regulated during brain development. Confocal microscopy of hippocampal neurons showed that ProSAP1 is predominantly localized in synapses, and immunoelectron microscopy in situ revealed a strong association with PSDs of hippocampal excitatory synapses. The accumulation of ProSAP1 at synaptic structures was analyzed in the developing cerebral cortex. During early postnatal development, strong immunoreactivity is detectable in neurites and somata, whereas from postnatal day 10 (P10) onward a punctate staining is observed. At the ultrastructural level, the immunoreactivity accumulates at developing PSDs starting from P8. Both interaction with the actin-binding protein cortactin and early appearance at postsynaptic sites suggest that ProSAP1/ CortBP1 may be involved in the assembly of the PSD during neuronal differentiation.

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Long-term potentiation and synaptic protein phosphorylation

Cited by 72 publications

References 59 publications

Training in the Morris water maze occludes the synergism between ACPD and arachidonic acid on glutamate release in synaptosomes prepared from rat hippocampus.

Training in the Morris water maze occludes the synergism between ACPD and arachidonic acid on glutamate release in synaptosomes prepared from rat hippocampus.

The effects of aging on gene expression in the hypothalamus and cortex of mice

Proline-Rich Synapse-Associated Protein-1/Cortactin Binding Protein 1 (ProSAP1/CortBP1) Is a PDZ-Domain Protein Highly Enriched in the Postsynaptic Density

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