Biology subjects

Badachhape, A.

Publications and source records attributed to Badachhape, A..

4 recordsLinked to original sources

bioRxiv2026

Microglia-Specific Molecular Magnetic Resonance Imaging Probe Enables Noninvasive Separation of Parkinsonian Mice from Controls

AbstractNeuroinflammation mediated by reactive microgliosis is a central driver of Parkinsons disease (PD) pathogenesis. This inflammatory process unfolds years before clinical symptoms, creating an opportunity for early intervention. In vivo imaging technologies that could detect and quantify microglial reactivity are therefore essential for early diagnosis, patient stratification, and evaluating emerging immunomodulatory therapies that target this fundamental driver of PD progression. Yet no standardized, sensitive, and specific technology currently achieves this goal. Molecular magnetic resonance imaging (mMRI) is uniquely suitable to address this problem because it integrates inherent high spatial resolution and soft-tissue contrast of conventional MRI with molecularly targeted contrast agents, enabling simultaneous acquisition of anatomical detail and functional/biological information at submillimeter isotropic resolution. Here we present a novel mMRI probe designed to specifically target colony stimulating factor-1 receptor, expressed primarily on microglia in the brain. In silico data show that the targeting ligand binds the extracellular Ig domain of the receptor. In vitro cell uptake studies with both murine and human microglia cell lines show that the probe binds the receptor triggering active cell uptake and in vivo MRI enabled effective separation of the A53T mouse model of Parkinsons disease from control mice using radiomics-assisted MR image analysis. Ex-vivo immunohistochemical analysis showed signal from the probe largely in the cytosolic compartment of IBA-1 reactive cells, confirming that the observed in vivo MRI signal is due primarily to retention of the agent by microglia. This novel technology has the potential to interrogate the rgional presentation of microglial activation in PD. One Sentence SummaryA microglia targeted MRI probe generates disease-specific contrast after injection, clearly distinguishing A53T Parkinsonian mice from controls.

neuroscience↗

bioRxiv2023

A dual target molecular MRI probe for noninvasive profiling of pathologic alpha-synuclein and microgliosis in a mouse model of Parkinson's disease

Parkinsons disease is characterized progressive deposition of pathologic alpha-synuclein (-syn) aggregates, neuroinflammation, and death of dopaminergic neurons in the substantia nigra projecting to the striatum. Noninvasive in vivo profiling of -syn aggregate accumulation and microgliosis by molecular imaging can provide insights on the underlying mechanisms of disease progression, facilitating the development of effective treatment. However, no classical imaging methods have been successful, despite several attempts. We demonstrate a novel method to noninvasive in vivo profiling of pathologic -syn in combination with microgliosis using molecular magnetic resonance imaging (MRI), by targeting oligomeric -syn in cerebrospinal fluid with nano scavengers (T) bearing a T1-relaxive Gd(III) payload. In this proof-of-concept report we demonstrate, in vitro, that microglia and neuroblastoma cell lines internalize cross-linked T/oligomeric -syn agglomerates. Delayed in vivo T1-weighted MRI scans following intravenous administration in the M83 -syn transgenic mouse line show statistically significant T1 signal enhancement in test mice versus controls. The in vivo data was validated by ex-vivo immunohistochemical analysis which showed a strong correlation between in vivo MRI signal enhancement, Lewy pathology distribution, and microglia activity in the treated brain tissue. Furthermore, neuronal, and microglial cells in brain tissue from treated mice displayed strong cytosolic signal originating from T, confirming in vivo cell uptake of the nano scavengers.

neuroscience↗

bioRxiv2021

HepT1-derived murine models of high-risk hepatoblastoma display vascular invasion, metastasis, and circulating tumor cells

Hepatoblastoma (HB) is the most common pediatric primary liver malignancy, and survival for high-risk disease approaches 50%. Mouse models of HB fail to recapitulate hallmarks of high-risk disease. The aim of this work was to generate murine models that show high-risk features including multifocal tumors, vascular invasion, metastasis, and circulating tumor cells (CTCs). HepT1 cells were injected into the livers or tail veins of mice, and tumor growth was monitored with magnetic resonance and bioluminescent imaging. Blood was analyzed with fluorescence activated cell sorting to identify CTCs. Intra- and extra-hepatic tumor samples were harvested for immunohistochemistry and RNA and DNA sequencing. Cell lines were grown from tumor samples and profiled with RNA sequencing. With intrahepatic injection of HepT1 cells, 100% of animals grew liver tumors and showed vascular invasion, metastasis, and CTCs. Mutation profiling revealed genetic alterations in seven cancer-related genes, while transcriptomic analyses showed changes in gene expression with cells that invade vessels. Tail vein injection of HepT1 cells resulted in multifocal, metastatic disease. These unique models will facilitate further meaningful studies of high-risk HB. Summary StatementIn this work, we developed and thoroughly characterized several unique models of hepatoblastoma derived from the HepT1 cell line that show high-risk features.

cancer biology↗

bioRxiv2021

Early Detection of Tau Pathology

While a definitive Alzheimers disease (AD) diagnosis remains a post-mortem exercise, the ATN Research Framework proposed by the National Institute on Aging and the Alzheimers Association utilizes a score representing the presence of amyloid deposits (A), tau deposits (T) and neuronal degeneration markers (N), with A+T+ necessary for a positive diagnosis. Current detection of tau pathology lags amyloid detection by years and by the time both markers are detected the disease is fairly advanced. We describe the development of a new generation of molecular imaging probes for in vivo detection of cells undergoing abnormal phosphorylation representing the initial stages of pTau pathology, potentially enabling a very early stage diagnosis of AD. We describe a novel nanoparticle formulation that binds such abnormally phosphorylating cells in a mouse model of tau pathology, enabling in vivo visualization of the hyperphosphorylative state by magnetic resonance imaging. Our results demonstrate the potential of this novel platform to identify a correlative marker signifying the development of future tau pathology, and has implications for early-stage diagnosis of Alzheimers disease.

neuroscience↗