Mariko Saito, PhD

Research Associate Professor, Department of Psychiatry

Summary

My research focuses on elucidating the mechanisms behind alcohol-induced acute damage in the developing brain, which leads to fetal alcohol spectrum disorder, a primary cause of intellectual disability. I also investigate the consequent long-lasting biochemical, anatomical, and electrophysiological changes that cause abnormal behavior in adult mice.

Our work in mouse models has led to several novel findings:

  • Alcohol alters lipid metabolism in the developing brain. These changes include elevations in ceramide, which is implicated in alcohol-induced apoptosis, and in GM2 gangliosides, which are implicated in alcohol-induced glial cell activation.
  • Alcohol inhibits AKT, AMP-activated protein kinase (AMPK), and activated glycogen synthase kinase 3 beta (GSK3B) in the developing brain, resulting in increased phosphorylation of tau.
  • Alcohol exposure in neonatal mice induces acute neurodegeneration and glial cell activation, as well as long-lasting anatomical, electrophysiological, and behavioral changes. Co-treatment with lithium, a GSK3B inhibitor, reverses these short- and long-term effects of alcohol exposure during development.
  • The major long-term cellular change induced by alcohol exposure during development is a specific decrease in parvalbumin interneurons, which is also observed in other developmental disorders.
  • Fragmented sleep, one of the long-lasting behavioral changes caused by alcohol exposure during development, may contribute to cognitive dysfunction.
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PhD from University of Tokyo

Zhang, Xiuli; Subbanna, Shivakumar; Williams, Colin R O; Canals-Baker, Stefanie; Hashim, Audrey; Wilson, Donald A; Weiss, Louis M; Shukla, Srushti; Chokkalingam, Parthiban; Das, Sasmita; Das, Bhaskar C; Saito, Mariko

Molecules : a journal of synthetic chemistry & natural product chemistry. 2025 Jan 31; 30(3):

Wilson, Donald A; Sullivan, Regina M; Smiley, John F; Saito, Mariko; Raineki, Charlis

Neuroscience & biobehavioral reviews. 2024 Feb 01; 105567

Zhang, Xiuli; Subbanna, Shivakumar; Williams, Colin R O; Canals-Baker, Stefanie; Smiley, John F; Wilson, Donald A; Das, Bhaskar C; Saito, Mariko

Neurochemical research. 2023 Jun; 48(6):1958-1970

Smiley, John F.; Bleiwas, Cynthia; Marino, Brandon M.; Vaddi, Prerana; Canals-Baker, Stefanie; Wilson, Donald A.; Saito, Mariko

Frontiers in neuroscience. 2023 Jan 01; 17:?-?

Wilson, Donald A.; Fleming, G.; Williams, C. R.O.; Teixeira, C. M.; Smiley, J. F.; Saito, Mariko

Frontiers in neuroscience. 2023 Jan 01; 17:?-?

D'Acunzo, Pasquale; Ungania, Jonathan M; Kim, Yohan; Barreto, Bryana R; DeRosa, Steven; Pawlik, Monika; Canals-Baker, Stefanie; Erdjument-Bromage, Hediye; Hashim, Audrey; Goulbourne, Chris N; Neubert, Thomas A; Saito, Mariko; Sershen, Henry; Levy, Efrat

Journal of extracellular vesicles. 2023 Jan; 12(1):e12301

Shah, Prachi; Kaneria, Aayush; Fleming, Gloria; Williams, Colin R O; Sullivan, Regina M; Lemon, Christian H; Smiley, John; Saito, Mariko; Wilson, Donald A

Frontiers in neuroscience. 2023 Nov; 17:1267542

Saito, Mariko; Subbanna, Shivakumar; Zhang, Xiuli; Canals-Baker, Stefanie; Smiley, John F; Wilson, Donald A; Das, Bhaskar C

Frontiers in neuroscience. 2023 Mar; 17:1170259