title: Extracellular matrix protein expression is brain region dependent.
abstract: In the brain, extracellular matrix (ECM) components form networks that contribute to structural and functional diversity. Maladaptive remodeling of ECM networks has been reported in neurodegenerative and psychiatric disorders, suggesting that the brain microenvironment is a dynamic structure. A lack of quantitative information about ECM distribution in the brain hinders an understanding of region-specific ECM functions and the role of ECM in health and disease. We hypothesized that each ECM protein as well as specific ECM structures, such as perineuronal nets (PNNs) and interstitial matrix, are differentially distributed throughout the brain, contributing to the unique structure and function in the various regions of the brain. To test our hypothesis, we quantitatively analyzed the distribution, colocalization, and protein expression of aggrecan, brevican, and tenascin-R throughout the rat brain utilizing immunohistochemistry and mass spectrometry analysis and assessed the effect of aggrecan, brevican, and/or tenascin-R on neurite outgrowth in vitro. We focused on aggrecan, brevican, and tenascin-R as they are especially expressed in the mature brain, and have established roles in brain development, plasticity, and neurite outgrowth. The results revealed a differentiated distribution of all three proteins throughout the brain and indicated that their presence significantly reduces neurite outgrowth in a 3D in vitro environment. These results underline the importance of a unique and complex ECM distribution for brain physiology and suggest that encoding the distribution of distinct ECM proteins throughout the brain will aid in understanding their function in physiology and in turn assist in identifying their role in disease. J. Comp. Neurol. 524:1309-1336, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Disease Biophysics Group, John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts, 02138.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Dauth
authors.affiliation: Disease Biophysics Group, John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts, 02138.
authors.forename: Thomas
authors.initials: T
authors.lastname: Grevesse
authors.affiliation: Translational Neuroscience Laboratory, McLean Hospital, Belmont, Massachusetts, 02478.|Department of Psychiatry, Harvard Medical School, Boston, Massachusetts, 02115.
authors.forename: Harry
authors.initials: H
authors.lastname: Pantazopoulos
authors.affiliation: Disease Biophysics Group, John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts, 02138.
authors.forename: Patrick H
authors.initials: PH
authors.lastname: Campbell
authors.affiliation: Disease Biophysics Group, John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts, 02138.
authors.forename: Ben M
authors.initials: BM
authors.lastname: Maoz
authors.affiliation: Translational Neuroscience Laboratory, McLean Hospital, Belmont, Massachusetts, 02478.|Department of Psychiatry, Harvard Medical School, Boston, Massachusetts, 02115.|Program in Neuroscience, Harvard Medical School, Boston, Massachusetts, 02115.
authors.forename: Sabina
authors.initials: S
authors.lastname: Berretta
authors.affiliation: Disease Biophysics Group, John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts, 02138.
authors.forename: Kevin Kit
authors.initials: KK
authors.lastname: Parker
mesh_terms: D053674:Aggrecans / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000033:anatomy & histology* / Q000378:metabolism*; D058581:Brevican / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D016326:Extracellular Matrix Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D021621:Imaging, Three-Dimensional; D013058:Mass Spectrometry; D009415:Nerve Net / Q000378:metabolism; D016501:Neurites / Q000378:metabolism; D059906:Neuroimaging; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D014404:Tubulin / Q000378:metabolism
chemical_list: D053674:Aggrecans; D058581:Brevican; D016326:Extracellular Matrix Proteins; C488416:Tubb3 protein, rat; D014404:Tubulin
keywords: RRID: AB_2207009; RRID: AB_398211; RRID: AB_90460; aggrecan; brain extracellular matrix; brevican; perineuronal nets; tenascin-R