Inhibition of Hippocampal Matrix Metalloproteinase-3 and -9 Disrupts Spatial Memory

Wright, John W.; Brown, Travis E.; Harding, Joseph W.

doi:https://doi.org/10.1155/2007/73813

Neural Plasticity

On this page

Abstract References Copyright Related Articles

Research Article | Open Access

Volume 2007 | Article ID 073813 | https://doi.org/10.1155/2007/73813

Inhibition of Hippocampal Matrix Metalloproteinase-3 and -9 Disrupts Spatial Memory

John W. Wright,^1,2,3Travis E. Brown,^2,3and Joseph W. Harding^1,2,3

Academic Editor: Carmen Sandi

Received06 Jul 2006

Revised21 Sept 2006

Accepted26 Sept 2006

Published13 Dec 2006

Abstract

Memory consolidation requires synaptic reconfiguration dependent upon extracellular matrix (ECM) molecules interacting with cell adhesion molecules. Matrix metalloproteinase (MMP) activity is responsible for transient alterations in the ECM that may be prerequisite to hippocampal-dependent learning. In support of this hypothesis we have measured increases in MMP-3 and MMP-9 levels within the hippocampus and prefrontal cortex during Morris water maze training. The present investigation extends these findings by determining that infusion of an MMP inhibitor (FN-439) into the dorsal hippocampus disrupted acquisition of this task. In vitro fluorescence enzyme assays to determine the specificity of FN-439 against the catalytic domains of MMP-3 and MMP-9 indicated mean ± SEM IC50s of 16.2 ± 7.8 and 210.5 ± 37.8 μM, respectively, while in situ zymography using hippocampal sections treated with FN-439 indicated significant reductions in MMP gelatinase activity. These results suggest that compromising the ability of the dorsal hippocampus to reconfigure ECM molecules by inhibiting MMP activity interferes with appropriate spatial memory acquisition, and support a role for hippocampal MMPs in the phenomena of spatial memory acquisition and storage.

References

J. Dzwonek, M. Rylski, and L. Kaczmarek, “Matrix metalloproteinases and their endogenous inhibitors in neuronal physiology of the adult brain,” FEBS Letters, vol. 567, no. 1, pp. 129–135, 2004.
View at: Publisher Site | Google Scholar
L. Kaczmarek, J. Lapinska-Dzwonek, and S. Szymczak, “Matrix metalloproteinases in the adult brain physiology: a link between c-Fos, AP-1 and remodeling of neuronal connections?” The EMBO Journal, vol. 21, no. 24, pp. 6643–6648, 2002.
View at: Publisher Site | Google Scholar
V. Nagy, O. Bozdagi, and A. Matynia, “Matrix metalloproteinase-9 is required for hippocampal late-phase long-term potentiation and memory,” The Journal of Neuroscience, vol. 26, no. 7, pp. 1923–1934, 2006.
View at: Publisher Site | Google Scholar
F. T. Bosman and I. Stamenkovic, “Functional structure and composition of the extracellular matrix,” The Journal of Pathology, vol. 200, no. 4, pp. 423–428, 2003.
View at: Publisher Site | Google Scholar
J. W. Wright and J. W. Harding, “The brain angiotensin system and extracellular matrix molecules in neural plasticity, learning, and memory,” Progress in Neurobiology, vol. 72, no. 4, pp. 263–293, 2004.
View at: Publisher Site | Google Scholar
A. Dityatev and M. Schachner, “Extracellular matrix molecules and synaptic plasticity,” Nature Reviews Neuroscience, vol. 4, no. 6, pp. 456–468, 2003.
View at: Publisher Site | Google Scholar
P. W. Frankland and B. Bontempi, “The organization of recent and remote memories,” Nature Reviews Neuroscience, vol. 6, no. 2, pp. 119–130, 2005.
View at: Publisher Site | Google Scholar
H. Birkedal-Hansen, “Proteolytic remodeling of extracellular matrix,” Current Opinion in Cell Biology, vol. 7, no. 5, pp. 728–735, 1995.
View at: Publisher Site | Google Scholar
V. M. Kahari and U. Saarialho-Kere, “Matrix metalloproteinases in skin,” Experimental Dermatology, vol. 6, no. 5, pp. 199–213, 1997.
View at: Publisher Site | Google Scholar
I. Stamenkovic, “Extracellular matrix remodelling: the role of matrix metalloproteinases,” The Journal of Pathology, vol. 200, no. 4, pp. 448–464, 2003.
View at: Publisher Site | Google Scholar
R. B. Nelson, D. J. Linden, C. Hyman, K. H. Pfenninger, and A. Routtenberg, “The two major phosphoproteins in growth cones are probably identical to two protein kinase C substrates correlated with persistence of long-term potentiation,” The Journal of Neuroscience, vol. 9, no. 2, pp. 381–389, 1989.
View at: Google Scholar
J. B. Sheffield, V. Krasnopolsky, and E. Dehlinger, “Inhibition of retinal growth cone activity by specific metalloproteinase inhibitors in vitro,” Developmental Dynamics, vol. 200, no. 1, pp. 79–88, 1994.
View at: Google Scholar
J. H. Uhm, N. P. Dooley, L. Y. Oh, and V. W. Yong, “Oligodendrocytes utilize a matrix metalloproteinase, MMP-9, to extend processes along an astrocyte extracellular matrix,” Glia, vol. 22, no. 1, pp. 53–63, 1998.
View at: Publisher Site | Google Scholar
C. Vaillant, M. Didier-Bazes, A. Hutter, M. F. Belin, and N. Thomasset, “Spatiotemporal expression patterns of metalloproteinases and their inhibitors in the postnatal developing rat cerebellum,” The Journal of Neuroscience, vol. 19, no. 12, pp. 4994–5004, 1999.
View at: Google Scholar
J. W. Skiles, N. C. Gonnella, and A. Y. Jeng, “The design, structure, and therapeutic application of matrix metalloproteinase inhibitors,” Current Medicinal Chemistry, vol. 8, no. 4, pp. 425–474, 2001.
View at: Google Scholar
R. Visse and H. Nagase, “Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry,” Circulation Research, vol. 92, no. 8, pp. 827–839, 2003.
View at: Publisher Site | Google Scholar
A. Szklarczyk, J. Lapinska, M. Rylski, R. D. McKay, and L. Kaczmarek, “Matrix metalloproteinase-9 undergoes expression and activation during dendritic remodeling in adult hippocampus,” The Journal of Neuroscience, vol. 22, no. 3, pp. 920–930, 2002.
View at: Google Scholar
J. W. Zhang, S. Deb, and P. E. Gottschall, “Regional and differential expression of gelatinases in rat brain after systemic kainic acid or bicuculline administration,” European Journal of Neuroscience, vol. 10, no. 11, pp. 3358–3368, 1998.
View at: Publisher Site | Google Scholar
T. M. Reeves, M. L. Prins, J. Zhu, J. T. Povlishock, and L. L. Phillips, “Matrix metalloproteinase inhibition alters functional and structural correlates of deafferentation-induced sprouting in the dentate gyrus,” The Journal of Neuroscience, vol. 23, no. 32, pp. 10182–10189, 2003.
View at: Google Scholar
G. Lynch, “Memory and the brain: unexpected chemistries and a new pharmacology,” Neurobiology of Learning and Memory, vol. 70, no. 1-2, pp. 82–100, 1998.
View at: Publisher Site | Google Scholar
Y. Nakagami, K. Abe, N. Nishiyama, and N. Matsuki, “Laminin degradation by plasmin regulates long-term potentiation,” The Journal of Neuroscience, vol. 20, no. 5, pp. 2003–2010, 2000.
View at: Google Scholar
J. K. Pinkstaff, J. Detterich, G. Lynch, and C. Gall, “Integrin subunit gene expression is regionally differentiated in adult brain,” The Journal of Neuroscience, vol. 19, no. 5, pp. 1541–1556, 1999.
View at: Google Scholar
L. C. Ronn, V. Berezin, and E. Bock, “The neural cell adhesion molecule in synaptic plasticity and ageing,” International Journal of Developmental Neuroscience, vol. 18, no. 2-3, pp. 193–199, 2000.
View at: Publisher Site | Google Scholar
T. Strekalova, M. Sun, M. Sibbe et al., “Fibronectin domains of extracellular matrix molecule tenascin-C modulate hippocampal learning and synaptic plasticity,” Molecular and Cellular Neuroscience, vol. 21, no. 1, pp. 173–187, 2002.
View at: Publisher Site | Google Scholar
J. W. Wright, E. A. Kramár, S. E. Meighan, and J. W. Harding, “Extracellular matrix molecules, long-term potentiation, memory consolidation and the brain angiotensin system,” Peptides, vol. 23, no. 1, pp. 221–246, 2002.
View at: Publisher Site | Google Scholar
J. W. Wright, E. S. Murphy, I. E. Elijah et al., “Influence of hippocampectomy on habituation, exploratory behavior, and spatial memory in rats,” Brain Research, vol. 1023, no. 1, pp. 1–14, 2004.
View at: Publisher Site | Google Scholar
S. E. Meighan, P. C. Meighan, P. Choudhury et al., “Effects of extracellular matrix-degrading proteases matrix metalloproteinases 3 and 9 on spatial learning and synaptic plasticity,” Journal of Neurochemistry, vol. 96, no. 5, pp. 1227–1241, 2006.
View at: Publisher Site | Google Scholar
J. Bures, A. A. Fenton, Yu. Kaminsky, and L. Zinyuk, “Place cells and place navigation,” Proceedings of the National Academy of Sciences of the United States of America, vol. 94, no. 1, pp. 343–350, 1997.
View at: Publisher Site | Google Scholar
B. L. McNaughton, C. A. Barnes, J. Meltzer, and R. J. Sutherland, “Hippocampal granule cells are necessary for normal spatial learning but not for spatially-selective pyramidal cell discharge,” Experimental Brain Research, vol. 76, no. 3, pp. 485–496, 1989.
View at: Google Scholar
R. G. Morris, P. Garrud, J. N. P. Rawlins, and J. O'Keefe, “Place navigation impaired in rats with hippocampal lesions,” Nature, vol. 297, no. 5868, pp. 681–683, 1982.
View at: Publisher Site | Google Scholar
H. Nishijo, T. Ono, S. Eifuku, and R. Tamura, “The relationship between monkey hippocampus place-related neural activity and action in space,” Neuroscience Letters, vol. 226, no. 1, pp. 57–60, 1997.
View at: Publisher Site | Google Scholar
I. Q. Whishaw, “Hippocampal, granule cell and ${CA}_{3 - 4}$ lesions impair formation of a place learning-set in the rat and induce reflex epilepsy,” Behavioural Brain Research, vol. 24, no. 1, pp. 59–72, 1987.
View at: Publisher Site | Google Scholar
G. H. Chen, Y. J. Wang, S. Qin, Q. G. Yang, J. N. Zhou, and R. Y. Liu, “Age-related spatial cognitive impairment is correlated with increase of synaptotagmin 1 in dorsal hippocampus in SAMP8 mice,” Neurobiology of Aging. In press.
View at: Google Scholar
S. Gaskin and N. M. White, “Cooperation and competition between the dorsal hippocampus and lateral amygdala in spatial discrimination learning,” Hippocampus, vol. 16, no. 7, pp. 577–585, 2006.
View at: Publisher Site | Google Scholar
J. W. Wright, L. A.. Stubley, E. S. Pederson, E. A. Kramár, J. M. Hanesworth, and J. W. Harding, “Contributions of the brain angiotensin IV- ${AT}_{4}$ receptor subtype system to spatial learning,” The Journal of Neuroscience, vol. 19, no. 10, pp. 3952–3961, 1999.
View at: Google Scholar
G. Paxinos and C. Watson, The Rat Brain in Stereotaxic Coordinates, Academic Press, New York, NY, 2nd edition, 1986.
S. Odake, Y. Morita, T. Morikawa, N. Yoshida, H. Hori, and Y. Nagai, “Inhibition of matrix metalloproteinases by peptidyl hydroxamic acids,” Biochemical and Biophysical Research Communications, vol. 199, no. 3, pp. 1442–1446, 1994.
View at: Publisher Site | Google Scholar
K. A. Roberts, L. T. Krebs, E. A. Kramár, M. J. Shaffer, J. W. Harding, and J. W. Wright, “Autoradiographic identification of brain angiotensin IV binding sites and differential c-Fos expression following intracerebroventricular injection of angiotensin II and IV in rats,” Brain Research, vol. 682, no. 1-2, pp. 13–21, 1995.
View at: Publisher Site | Google Scholar
O. Bukalo, M. Schachner, and A. Dityatev, “Modification of extracellular matrix by enzymatic removal of chondroitin sulfate and by lack of tenascin-R differentially affects several forms of synaptic plasticity in the hippocampus,” Neuroscience, vol. 104, no. 2, pp. 359–369, 2001.
View at: Publisher Site | Google Scholar
K. B. Hoffman, “The relationship between adhesion molecules and neuronal plasticity,” Cellular and Molecular Neurobiology, vol. 18, no. 5, pp. 461–475, 1998.
View at: Publisher Site | Google Scholar
M. Kaksonen, I. Pavlov, V. Voikar et al., “Syndecan-3-deficient mice exhibit enhanced LTP and impaired hippocampus-dependent memory,” Molecular and Cellular Neuroscience, vol. 21, no. 1, pp. 158–172, 2002.
View at: Publisher Site | Google Scholar
I. Pavlov, V. Voikar, M. Kaksonen et al., “Role of heparin-binding growth-associated molecule (HB-GAM) in hippocampal LTP and spatial learning revealed by studies on overexpressing and knockout mice,” Molecular and Cellular Neuroscience, vol. 20, no. 2, pp. 330–342, 2002.
View at: Publisher Site | Google Scholar

Copyright

Copyright © 2007 John W. Wright et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

PDF Download Citation Order printed copies

Views

295

Downloads

892

Citations