Microglia Depletion-Induced Remodeling of Extracellular Matrix and Excitatory Synapses in the Hippocampus of Adult Mice

Strackeljan, Luisa; Baczynska, Ewa; Cangalaya, Carla; Baidoe-Ansah, David; Wlodarczyk, Jakub; Kaushik, Rahul; Dityatev, Alexander

doi:10.3390/cells10081862

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Microglia Depletion-Induced Remodeling of Extracellular Matrix and Excitatory Synapses in the Hippocampus of Adult Mice

¹,

^1,3,4,

²,

^1,* and

^1,5,6,*

Molecular Neuroplasticity, German Center for Neurodegenerative Diseases (DZNE), 39120 Magdeburg, Germany

Nencki Institute of Experimental Biology, Polish Academy of Sciences, Pasteura 3, 02-093 Warsaw, Poland

Institut für Biochemie und Zellbiologie, Medical Faculty, Otto-von-Guericke-University, 39120 Magdeburg, Germany

⁴

ESF International Graduate School on Analysis, Imaging and Modelling of Neuronal and Inflammatory Processes, 39120 Magdeburg, Germany

⁵

Center for Behavioral Brain Sciences (CBBS), 39106 Magdeburg, Germany

⁶

Medical Faculty, Otto-von-Guericke University, 39120 Magdeburg, Germany

Authors to whom correspondence should be addressed.

Academic Editors: Alexander E. Kalyuzhny and Marta Fumagalli

Cells 2021, 10(8), 1862; https://doi.org/10.3390/cells10081862

Received: 31 May 2021 / Revised: 15 July 2021 / Accepted: 20 July 2021 / Published: 22 July 2021

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Abstract

The extracellular matrix (ECM) plays a key role in synaptogenesis and the regulation of synaptic functions in the central nervous system. Recent studies revealed that in addition to dopaminergic and serotoninergic neuromodulatory systems, microglia also contribute to the regulation of ECM remodeling. In the present work, we investigated the physiological role of microglia in the remodeling of perineuronal nets (PNNs), predominantly associated with parvalbumin-immunopositive (PV+) interneurons, and the perisynaptic ECM around pyramidal neurons in the hippocampus. Adult mice were treated with PLX3397 (pexidartinib), as the inhibitor of colony-stimulating factor 1 receptor (CSF1-R), to deplete microglia. Then, confocal analysis of the ECM and synapses was performed. Although the elimination of microglia did not alter the overall number or intensity of PNNs in the CA1 region of the hippocampus, it decreased the size of PNN holes and elevated the expression of the surrounding ECM. In the neuropil area in the CA1 str. radiatum, the depletion of microglia increased the expression of perisynaptic ECM proteoglycan brevican, which was accompanied by the elevated expression of presynaptic marker vGluT1 and the increased density of dendritic spines. Thus, microglia regulate the homeostasis of pre- and postsynaptic excitatory terminals and the surrounding perisynaptic ECM as well as the fine structure of PNNs enveloping perisomatic—predominantly GABAergic—synapses. View Full-Text

Keywords: extracellular matrix; synapses; parvalbumin; brevican; microglia; perineuronal nets; perisynaptic ECM

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MDPI and ACS Style

Strackeljan, L.; Baczynska, E.; Cangalaya, C.; Baidoe-Ansah, D.; Wlodarczyk, J.; Kaushik, R.; Dityatev, A. Microglia Depletion-Induced Remodeling of Extracellular Matrix and Excitatory Synapses in the Hippocampus of Adult Mice. Cells 2021, 10, 1862. https://doi.org/10.3390/cells10081862

AMA Style

Strackeljan L, Baczynska E, Cangalaya C, Baidoe-Ansah D, Wlodarczyk J, Kaushik R, Dityatev A. Microglia Depletion-Induced Remodeling of Extracellular Matrix and Excitatory Synapses in the Hippocampus of Adult Mice. Cells. 2021; 10(8):1862. https://doi.org/10.3390/cells10081862

Chicago/Turabian Style

Strackeljan, Luisa, Ewa Baczynska, Carla Cangalaya, David Baidoe-Ansah, Jakub Wlodarczyk, Rahul Kaushik, and Alexander Dityatev. 2021. "Microglia Depletion-Induced Remodeling of Extracellular Matrix and Excitatory Synapses in the Hippocampus of Adult Mice" Cells 10, no. 8: 1862. https://doi.org/10.3390/cells10081862

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Microglia Depletion-Induced Remodeling of Extracellular Matrix and Excitatory Synapses in the Hippocampus of Adult Mice

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