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Cited by 340

The DOI matches its Crossref record; 33 of the 33 references it cites were found in a registry or an index.

Regulation of late-phase LTP and long-term memory in normal and aging hippocampus: role of secreted proteins tPA and BDNF

Pang, Petti T., Lu, Bai·2004·Ageing Research Reviews
DOI 10.1016/j.arr.2004.07.002
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Abstract

Long-lasting forms of memory are generally believed to be mediated by protein synthesis-dependent, late-phase long-term potentiation (L-LTP). L-LTP exhibits at least two distinctive characteristics compared with early phase LTP (E-LTP): synaptic growth and requirement of gene transcription and new protein synthesis. In this review, we discuss the cellular and molecular mechanisms underlying the structural and functional changes of hippocampal synapses during L-LTP, in the context of long-term memory. We describe experiments that reveal the critical role of cAMP/protein kinase A and MAP kinase pathways, and the downstream transcription factor CREB. Because transcription-dependent long-term changes are input specific, we also discuss the role of "local protein synthesis" and "synaptic tagging" mechanisms that may confer synapse specificity. We then focus on brain-derived neurotrophic factor (BDNF) and tissue plasminogen activator (tPA), two secreted proteins that have been repeatedly implicated in L-LTP. Biochemical and molecular biology experiments indicate that the expression and secretion of both factors are enhanced by strong tetanic stimulation that induces L-LTP as well as by training in hippocampal-dependent memory tasks. Inhibition of either tPA or BDNF by gene knockout and specific inhibitors results in a significant impairments in L-LTP and long-term memory. Further work will be required to address the relationship between BDNF and tPA in various forms of synaptic plasticity, and the mechanisms by which BDNF/tPA achieves synapse-specific modulation. Finally, we discuss how the aging process affects L-LTP and long-term memory.

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Metadata

Authors
Pang, P. T., & Lu, B.
Venue
Ageing Research Reviews
Publisher
Elsevier BV
Published
2004-11
Volume
3
Issue
4
Pages
407-430
ISSN
1568-1637 (ISSN-L)
DOI
10.1016/j.arr.2004.07.002
OpenAlex
W2027973075
Cited by
340
References
33
FWCI
0.87
Type
journal article
Language
en
Open access
closed

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