Biology subjects

Ainslie, A. P.

Publications and source records attributed to Ainslie, A. P..

3 recordsLinked to original sources

bioRxiv2023

Radiotherapy induces persistent innate immune reprogramming of microglia into a primed state

More than half of all brain tumour survivors experience debilitating and often progressive cognitive decline after treatment with radiotherapy. Microglia, the resident macrophages in the brain, have been implicated in this decline. In response to various insults microglia can develop innate immune memory (IIM), which can either enhance (priming) or repress (tolerance) the response to subsequent inflammatory challenges. Here, we investigated whether radiation affects the IIM of microglia by irradiating the brains of rats and later exposing them to a secondary inflammatory stimulus. Comparative transcriptomic profiling and protein validation of microglia isolated from irradiated rats showed a stronger immune response to a secondary inflammatory insult demonstrating that radiation can lead to long-lasting molecular reprogramming of microglia. Transcriptomic analysis of post-mortem normal-appearing non-tumour brain tissue of glioblastoma patients indicates that radiation-induced microglial priming is conserved in humans. Targeting microglial priming after radiotherapy or avoiding further inflammatory insults could decrease radiotherapy-induced neurotoxicity.

neuroscience↗

bioRxiv2022

Glioblastoma is associated with extensive accelerated brain ageing

Progressive neurocognitive dysfunction is the leading cause of a reduced quality of life in patients with primary brain tumours. Understanding the mechanisms underlying cognitive impairments that occur in response to a brain tumour and its treatment is essential to improve patients quality of life. Here, we show that normal-appearing non-tumour brain regions of patients with glioblastoma display hallmarks of accelerated ageing and share multiple features with Alzheimers disease patients. Integrated transcriptomic and tissue analysis shows that normal-appearing brain tissue from glioblastoma patients has a significant overlap with brain tissue from Alzheimers disease patients, revealing shared mitochondrial and neuronal dysfunction, and proteostasis deregulation. Overall, the brain of glioblastoma patients undergoes Alzheimers disease-like accelerated ageing, providing novel or repurposed therapeutic targets for managing brain cancer-related side effects.

neuroscience↗

bioRxiv2020

ECM remodeling and spatial cell cycle coordination determine tissue growth kinetics

During development, multicellular organisms undergo stereotypical patterns of tissue growth to yield organs of highly reproducible sizes and shapes. How this process is orchestrated remains unclear. Analysis of the temporal dynamics of tissue growth in the Drosophila abdomen reveals that cell cycle times are spatially correlated and that growth termination occurs through the rapid emergence of a population of arrested cells rather than a gradual slowing down of cell cycle time. Reduction in apical tension associated with tissue crowding has been proposed as a developmental growth termination mechanism. Surprisingly, we find that growth arrest in the abdomen occurs while apical tension increases, showing that in this tissue a reduction in tension does not underlie the mechanism of growth arrest. However, remodeling of the extracellular matrix is necessary for tissue expansion. Thus, changes in the tissue microenvironment, and a rapid exit from proliferation, control the formation of the adult Drosophila abdomen.

developmental biology↗