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Glutamate Receptors Mediate Changes to Dendritic Mitochondria in Neurons Grown on Stiff Substrates

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Abstract

The stiffness of brain tissue changes during development and disease. These changes can affect neuronal morphology, specifically dendritic arborization. We previously reported that N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors regulate dendrite number and branching in a manner that is dependent on substrate stiffness. Since mitochondria affect the shape of dendrites, in this study, we determined whether the stiffness of substrates on which rat hippocampal neurons are grown affects mitochondrial characteristics and if glutamate receptors mediate the effects of substrate stiffness. Dendritic mitochondria are small, short, simple, and scarce in neurons cultured on substrates of 0.5 kPa stiffness. In contrast, dendritic mitochondria are large, long, complex, and low in number in neurons grown on substrates of 4 kPa stiffness. Dendritic mitochondria of neurons cultured on glass are high in number and small with complex shapes. Treatment of neurons grown on the stiffer gels or glass with the NMDA and AMPA receptor antagonists, 2-amino-5-phosphonopentanoic acid and 6-cyano-7-nitroquinoxaline-2,3-dione, respectively, results in mitochondrial characteristics of neurons grown on the softer substrate. These results suggest that glutamate receptors play important roles in regulating both mitochondrial morphology and dendritic arborization in response to substrate stiffness.

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Acknowledgments

This work was supported by New Jersey Commission Brain Injury Research grants # CBIR14PIL005 (to N.N.B.) and CBIR14IRG019 (to B.L.F.), a Rutgers Division of Life Sciences Summer Undergraduate Research Fellowship (to S.K.), and a Rutgers Aresty Undergraduate Research Fellowship (to A.J.K.). A.O. was supported by New Jersey Commission Brain Injury Research fellowship # CBIR19FEL018 and National Institutes of Health Biotechnology Training Grant T32 GM008339-20.

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Author notes

  1. Siddhant Kumarapuram and Ansley J. Kunnath have contributed equally to this work.

Authors and Affiliations

  1. Department of Cell Biology and Neuroscience, Rutgers University, 604 Allison Road, Piscataway, NJ, 08854-8082, USA

    Siddhant Kumarapuram, Ansley J. Kunnath, Anton Omelchenko & Bonnie L. Firestein

  2. Neurosciences Graduate Program, Rutgers, The State University of New Jersey, Piscataway, NJ, USA

    Anton Omelchenko

  3. Department of Biomedical Engineering, Rutgers, The State University of New Jersey, Piscataway, NJ, USA

    Nada N. Boustany

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  1. Siddhant Kumarapuram
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Contributions

SK: Data curation; Formal analysis; Methodology; Visualization; Writing—original draft. AJK: Data curation; Formal analysis; Investigation; Methodology; Visualization; Writing—review & editing; AO: Investigation; Methodology; NNB: Conceptualization; Funding acquisition; Methodology; Project administration; Resources; Supervision; Visualization; Writing—review & editing. BLF: Conceptualization; Funding acquisition; Methodology; Project administration; Resources; Supervision; Visualization; Writing—original draft; Writing—review & editing.

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Correspondence to Bonnie L. Firestein.

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Kumarapuram, S., Kunnath, A.J., Omelchenko, A. et al. Glutamate Receptors Mediate Changes to Dendritic Mitochondria in Neurons Grown on Stiff Substrates. Ann Biomed Eng 50, 1116–1133 (2022). https://doi.org/10.1007/s10439-022-02987-0

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