Biology subjects

Hama, H.

Publications and source records attributed to Hama, H..

3 recordsLinked to original sources

bioRxiv2026

OxyBLI: A Genetics-Based Approach for In Vivo Real-Time Visualization of Tissue Oxygenation Dynamics

Accurate measurement of cellular oxygen levels is essential for understanding the balance between oxygen demand and supply in tissues. However, conventional methods only yield compromised results. We harnessed the oxygen dependence of bioluminescence to develop OxyBLI--a noninvasive optical method that directly monitors oxygen levels in specific cell populations of intact experimental animals. We characterized OxyBLI signals across various critical situations associated with common interventions. Hypoxic breathing and subsequent systemic tissue hypoxia caused blood to be redistributed in a way that prioritized brain oxygenation. In contrast, hyperoxic breathing sharply increased tissue oxygenation, which promptly returned to the target level owing to a vasoconstrictor response. These findings are expected to help resolve the long-standing clinical issue regarding the risks and benefits of administering supplemental oxygen to acutely ill patients. Our multifaceted approach, which presents multiple challenges to individual animals over time, will advance our understanding of the delicate interaction between hypoxia and hyperoxia.

physiology↗

bioRxiv2024

Single MAPT knock-in mouse models of frontotemporal dementia for sharing with the neurodegenerative research community

We recently reported development of human MAPT knock-in mice that carry single or double pathogenic mutations of frontotemporal dementia. However, it takes more than 14 months for the line with the most aggressive phenotypes to exhibit tau pathology without forming high-order tau oligomers, along with concomitant abnormal behavior. We thus generated MAPT knock-in mice carrying triple mutations, among which the MAPTP301S;Int10+3;S320F line exhibited robust pathology starting earlier than 6 months. Tau accumulation took place mainly in the thalamus, hypothalamus, amygdala and entorhinal cortex, but less so in the hippocampus, leading to synaptic loss, atrophy and behavioral abnormalities. Crossbreeding MAPTP301S;Int10+3;S320F with App knock-in mice AppNL-G-F resulted in the manifestation of tau pathology in the hippocampus and cortex. These mutant mice will be valuable tools for understanding the mechanisms of frontotemporal dementia, Alzheimers disease and other tauopathies.

neuroscience↗

bioRxiv2024

Plaque-associated endogenous IgG and its impact on immunohistochemical detection of mouse monoclonal IgG antibodies in mouse models of Alzheimer's disease

Experimental studies for Alzheimers disease (AD) have largely depended on transgenic mice with {beta}-amyloidosis. Here, we report plaque-associated endogenous immunoglobulin G (PA-IgG) and its impact on indirect immunohistochemical detection of mouse monoclonal IgG antibodies (Ms monoclonal IgG Abs) in the brain of AD mouse models. Immunostaining for Ms IgG in AD mouse models demonstrated endogenous IgG in the brain parenchyma accumulated on microglia associated with amyloid {beta} (A{beta}) plaques and/or A{beta} plaques themselves. This PA-IgG caused robust off-target binding of secondary Abs against Ms IgG (H+L) in indirect immunohistochemistry using Ms monoclonal IgG Abs. Blocking with Fab fragments of anti-Ms IgG (H+L) Ab was not effective against off-target binding. Unexpectedly, we found that secondary Abs that specifically recognize Ms IgG1, 2a, 2b, and 3 did not cause off-target binding on frozen brain sections of AppNL-G-F/NL-G-Fmice, and enabled specific labeling of Ms monoclonal IgG Abs in the AD mouse model brains. We further demonstrated that indirect detection with a conventional secondary Ab against Ms IgG (H+L) Ab could lead to erroneous conclusions regarding A{beta} plaque burden and phosphorylated tau accumulation in AppNL-G-F/NL-G-Fmice, and the use of Ms IgG subclass specific secondary Abs allowed to avoid the inevitable impediment caused by the endogenous IgG accumulation. Specific indirect detection of Ms monoclonal IgG Abs in AD mouse models by the use of secondary Abs against Ms IgG subclass would accelerate AD research by expanding the choice of Abs available for histochemical analysis in AD studies.

neuroscience↗