Extracellular Matrix Regulation in Physiology and in Brain Disease

Soles, Alyssa; Selimovic, Adem; Sbrocco, Kaelin; Ghannoum, Ferris; Hamel, Katherine; Moncada, Emmanuel Labrada; Gilliat, Stephen; Cvetanovic, Marija

doi:10.3390/ijms24087049

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Extracellular Matrix Regulation in Physiology and in Brain Disease

by

Alyssa Soles

¹

,

Adem Selimovic

^1,†

,

Kaelin Sbrocco

^1,†,

Ferris Ghannoum

¹,

Katherine Hamel

¹

,

Emmanuel Labrada Moncada

¹

,

Stephen Gilliat

¹

and

Marija Cvetanovic

^1,2,*

¹

Department of Neuroscience, University of Minnesota, 321 Church St SE, Minneapolis, MN 55455, USA

²

Institute for Translational Neuroscience, University of Minnesota, 2101 6th Street SE, Minneapolis, MN 55455, USA

^*

Author to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Int. J. Mol. Sci. 2023, 24(8), 7049; https://doi.org/10.3390/ijms24087049

Submission received: 28 February 2023 / Revised: 31 March 2023 / Accepted: 7 April 2023 / Published: 11 April 2023

(This article belongs to the Special Issue Gene Regulation in Brain Development and Physiology)

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Abstract

The extracellular matrix (ECM) surrounds cells in the brain, providing structural and functional support. Emerging studies demonstrate that the ECM plays important roles during development, in the healthy adult brain, and in brain diseases. The aim of this review is to briefly discuss the physiological roles of the ECM and its contribution to the pathogenesis of brain disease, highlighting the gene expression changes, transcriptional factors involved, and a role for microglia in ECM regulation. Much of the research conducted thus far on disease states has focused on “omic” approaches that reveal differences in gene expression related to the ECM. Here, we review recent findings on alterations in the expression of ECM-associated genes in seizure, neuropathic pain, cerebellar ataxia, and age-related neurodegenerative disorders. Next, we discuss evidence implicating the transcription factor hypoxia-inducible factor 1 (HIF-1) in regulating the expression of ECM genes. HIF-1 is induced in response to hypoxia, and also targets genes involved in ECM remodeling, suggesting that hypoxia could contribute to ECM remodeling in disease conditions. We conclude by discussing the role microglia play in the regulation of the perineuronal nets (PNNs), a specialized form of ECM in the central nervous system. We show evidence that microglia can modulate PNNs in healthy and diseased brain states. Altogether, these findings suggest that ECM regulation is altered in brain disease, and highlight the role of HIF-1 and microglia in ECM remodeling.

Keywords: extracellular matrix; regulation; gene expression; microglia; neurons; HIF-1; perineuronal nets

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MDPI and ACS Style

Soles, A.; Selimovic, A.; Sbrocco, K.; Ghannoum, F.; Hamel, K.; Moncada, E.L.; Gilliat, S.; Cvetanovic, M. Extracellular Matrix Regulation in Physiology and in Brain Disease. Int. J. Mol. Sci. 2023, 24, 7049. https://doi.org/10.3390/ijms24087049

AMA Style

Soles A, Selimovic A, Sbrocco K, Ghannoum F, Hamel K, Moncada EL, Gilliat S, Cvetanovic M. Extracellular Matrix Regulation in Physiology and in Brain Disease. International Journal of Molecular Sciences. 2023; 24(8):7049. https://doi.org/10.3390/ijms24087049

Chicago/Turabian Style

Soles, Alyssa, Adem Selimovic, Kaelin Sbrocco, Ferris Ghannoum, Katherine Hamel, Emmanuel Labrada Moncada, Stephen Gilliat, and Marija Cvetanovic. 2023. "Extracellular Matrix Regulation in Physiology and in Brain Disease" International Journal of Molecular Sciences 24, no. 8: 7049. https://doi.org/10.3390/ijms24087049

APA Style

Soles, A., Selimovic, A., Sbrocco, K., Ghannoum, F., Hamel, K., Moncada, E. L., Gilliat, S., & Cvetanovic, M. (2023). Extracellular Matrix Regulation in Physiology and in Brain Disease. International Journal of Molecular Sciences, 24(8), 7049. https://doi.org/10.3390/ijms24087049

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Extracellular Matrix Regulation in Physiology and in Brain Disease

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