The paper identifies brain-peripheral DNA methylation sites (BrESS) that consistently predict brain methylation across tissues, showing they are not linked to disease heritability.

bioRxiv · Oct 24, 2026 · PreprintNeuroscience

Zuranolone mitigates delirium-like bispectral EEG changes, behavioral deficits, and neuroinflammation across surgical and inflammatory mouse models and age groups

Bun Aoyama, Shota Nishitani, Kyosuke Yamanishi, Hieu Dinh Nguyen, Rika Sakuma, Takaya Ishii, Yukiko Ikeda, Tsuyoshi Nishiguchi, Ilgin Genc, Nathan James Phuong, Nipun Gorantla, Tomoteru Seki, Akiyoshi Shimura, Takashi Kawano, Gen Shinozaki

bioRxiv · May 21, 2026 · PreprintNeuroscience

Non-linear Age-related Change in Human Interleukin-11 and the receptor subunit alpha DNA Methylation

Akiyoshi Shimura, Varun Bhamidipati Dwaraka, Kyosuke Yamanishi, Tomoteru Seki, Tsuyoshi Nishiguchi, Bun Aoyama, Takaya Ishii, Nathan James Phuong, Nipun Gorantla, Hieu Dinh Nguyen, Therese Anne Santiago, Shota Nishitani, Ryan C. Smith, Gen Shinozaki

The paper examines age-related DNA methylation changes in IL-11 and IL-11RA genes, finding inverse U-shaped patterns that suggest non-linear regulation of IL-11 expression and sensitivity across life stages.

Biochemistry and Biophysics Reports · Mar 19, 2026Peer-reviewedGenetics

Epigenetic markers of middle-age: non-linear DNA methylation changes with aging in humans

Akiyoshi Shimura, Kyosuke Yamanishi, Takaya Ishii, Tomoteru Seki, Tsuyoshi Nishiguchi, Bun Aoyama, Therese Santiago, Varun Bhamidipati Dwaraka, Ryan C. Smith, Gen Shinozaki

The paper identifies non-linear DNA methylation patterns with aging, showing peaks or troughs in middle age and linking them to disease onset.

bioRxiv · Aug 14, 2025 · PreprintGenomics

The age-related susceptibility to postoperative delirium quantified by bispectral electroencephalography (BSEEG) correlates with postoperative delirium-like behavior in mice

Tsuyoshi Nishiguchi, Kyosuke Yamanishi, Akiyoshi Shimura, Tomoteru Seki, Takaya Ishii, Bun Aoyama, Nipun Gorantla, Hieu Dinh Nguyen, Nathan James Phuong, Takehiko Yamanashi, Masaaki Iwata, Gen Shinozaki

This study correlates BSEEG scores with delirium-like behavior in mice, showing age-related differences in the relationship between BSEEG and behavioral outcomes.

Psychiatry and Clinical Neurosciences Reports · Jul 6, 2025Peer-reviewedAnimal Behavior & Cognition

Glial Contribution to the Pathogenesis of Post-Operative Delirium Revealed by Multi-omic Analysis of Brain Tissue from Neurosurgery Patients

Takaya Ishii, Tao Wang, Kazuki Shibata, Shota Nishitani, Takehiko Yamanashi, Nadia E. Wahba, Tomoteru Seki, Kaitlyn J. Thompson, Kyosuke Yamanishi, Tsuyoshi Nishiguchi, Akiyoshi Shimura, Bun Aoyama, Nipun Gorantla, Nathan James Phuong, Hieu Dinh Nguyen, , Gen Shinozaki

This study uses multi-omic analysis of brain tissue from POD patients to show glial cell contributions to pathogenesis, identifying epigenetic and transcriptomic changes in microglia and astrocytes.

bioRxiv · Mar 13, 2025 · PreprintNeuroscience

LPS-induced delirium-like behavior and microglial activation in mice correlate with bispectral electroencephalography (BSEEG)

Tsuyoshi Nishiguchi, Kyosuke Yamanishi, Nipun Gorantla, Akiyoshi Shimura, Tomoteru Seki, Takaya Ishii, Bun Aoyama, Johnny R. Malicoat, Nathan James Phuong, Nicole Jade Dye, Takehiko Yamanashi, Masaaki Iwata, Gen Shinozaki

This study validates the use of BSEEG in an LPS-induced mouse model of delirium, showing its correlation with behavioral changes and microglial activation.

The Journals of Gerontology Series A · Nov 2, 2024Peer-reviewedNeuroscience