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Effect of myristoylated alanine-rich C kinase substrate (MARCKS) overexpression on hippocampus-dependent learning and hippocampal synaptic plasticity in MARCKS transgenic mice.
Hippocampus 2005; 15(5):675-83H

Abstract

The myristoylated alanine-rich C kinase substrate (MARCKS) is a primary substrate of protein kinase C (PKC) thought to regulate membrane-filamentous actin cytoskeletal plasticity in response to PKC activity in the regulation of synaptic efficacy. We have recently reported that MARCKS expression is significantly elevated (45%) in the hippocampus of DBA/2J mice, which exhibit impaired hippocampus-dependent learning and hippocampal long-term potentiation (LTP), compared with C57BL/6J mice. The latter finding led us to hypothesize that elevations in MARCKS expression are detrimental to hippocampal plasticity and function. To assess this more directly, we examined hippocampal (CA1) paired-pulse facilitation and LTP, and hippocampus-dependent learning in mice overexpressing MARCKS through the expression of a human MARCKS transgene (Tg+). The human MARCKS protein was confirmed to be expressed in the hippocampus of Tg+ mice but not in Tg- mice. Schaffer collateral paired-pulse facilitation, input-output responses, and LTP did not differ between Tg+ and Tg- mice, indicating that neurotransmitter release, short-term, and long-term synaptic plasticity are not impaired by MARCKS overexpression. In the Morris water maze, Tg+ mice exhibited a mild but significant spatial learning impairment during initial acquisition, and a more severe impairment during reversal training. Tg+ did not exhibit impaired swim speed or visible platform performance relative to Tg- mice, indicating the absence of gross sensorimotor deficits. Fear conditioning to either context or cue was not impaired in Tg+ mice. Behavioral deficits could not be attributed to differences in hippocampal PKC isozyme (alpha beta(II), gamma, epsilon, zeta) or calmodulin expression, or alterations in hippocampal cytoarchitecture or infrapyramidal mossy fiber limb length. Collectively, these results indicate that elevations in MARCKS expression are detrimental to specific aspects of hippocampal function.

Authors+Show Affiliations

Department of Psychiatry, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0559, USA. robert.mcnamara@psychiatry.uc.edu

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15889447

Citation

McNamara, Robert K., et al. "Effect of Myristoylated Alanine-rich C Kinase Substrate (MARCKS) Overexpression On Hippocampus-dependent Learning and Hippocampal Synaptic Plasticity in MARCKS Transgenic Mice." Hippocampus, vol. 15, no. 5, 2005, pp. 675-83.
McNamara RK, Hussain RJ, Simon EJ, et al. Effect of myristoylated alanine-rich C kinase substrate (MARCKS) overexpression on hippocampus-dependent learning and hippocampal synaptic plasticity in MARCKS transgenic mice. Hippocampus. 2005;15(5):675-83.
McNamara, R. K., Hussain, R. J., Simon, E. J., Stumpo, D. J., Blackshear, P. J., Abel, T., & Lenox, R. H. (2005). Effect of myristoylated alanine-rich C kinase substrate (MARCKS) overexpression on hippocampus-dependent learning and hippocampal synaptic plasticity in MARCKS transgenic mice. Hippocampus, 15(5), pp. 675-83.
McNamara RK, et al. Effect of Myristoylated Alanine-rich C Kinase Substrate (MARCKS) Overexpression On Hippocampus-dependent Learning and Hippocampal Synaptic Plasticity in MARCKS Transgenic Mice. Hippocampus. 2005;15(5):675-83. PubMed PMID: 15889447.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of myristoylated alanine-rich C kinase substrate (MARCKS) overexpression on hippocampus-dependent learning and hippocampal synaptic plasticity in MARCKS transgenic mice. AU - McNamara,Robert K, AU - Hussain,Rifat J, AU - Simon,Erica J, AU - Stumpo,Deborah J, AU - Blackshear,Perry J, AU - Abel,Ted, AU - Lenox,Robert H, PY - 2005/5/13/pubmed PY - 2005/9/8/medline PY - 2005/5/13/entrez SP - 675 EP - 83 JF - Hippocampus JO - Hippocampus VL - 15 IS - 5 N2 - The myristoylated alanine-rich C kinase substrate (MARCKS) is a primary substrate of protein kinase C (PKC) thought to regulate membrane-filamentous actin cytoskeletal plasticity in response to PKC activity in the regulation of synaptic efficacy. We have recently reported that MARCKS expression is significantly elevated (45%) in the hippocampus of DBA/2J mice, which exhibit impaired hippocampus-dependent learning and hippocampal long-term potentiation (LTP), compared with C57BL/6J mice. The latter finding led us to hypothesize that elevations in MARCKS expression are detrimental to hippocampal plasticity and function. To assess this more directly, we examined hippocampal (CA1) paired-pulse facilitation and LTP, and hippocampus-dependent learning in mice overexpressing MARCKS through the expression of a human MARCKS transgene (Tg+). The human MARCKS protein was confirmed to be expressed in the hippocampus of Tg+ mice but not in Tg- mice. Schaffer collateral paired-pulse facilitation, input-output responses, and LTP did not differ between Tg+ and Tg- mice, indicating that neurotransmitter release, short-term, and long-term synaptic plasticity are not impaired by MARCKS overexpression. In the Morris water maze, Tg+ mice exhibited a mild but significant spatial learning impairment during initial acquisition, and a more severe impairment during reversal training. Tg+ did not exhibit impaired swim speed or visible platform performance relative to Tg- mice, indicating the absence of gross sensorimotor deficits. Fear conditioning to either context or cue was not impaired in Tg+ mice. Behavioral deficits could not be attributed to differences in hippocampal PKC isozyme (alpha beta(II), gamma, epsilon, zeta) or calmodulin expression, or alterations in hippocampal cytoarchitecture or infrapyramidal mossy fiber limb length. Collectively, these results indicate that elevations in MARCKS expression are detrimental to specific aspects of hippocampal function. SN - 1050-9631 UR - https://www.unboundmedicine.com/medline/citation/15889447/Effect_of_myristoylated_alanine_rich_C_kinase_substrate__MARCKS__overexpression_on_hippocampus_dependent_learning_and_hippocampal_synaptic_plasticity_in_MARCKS_transgenic_mice_ L2 - https://doi.org/10.1002/hipo.20089 DB - PRIME DP - Unbound Medicine ER -