Untangling the connections between inflammation, aging and Parkinson’s disease
Inflammation is a process that occurs in the body as a response to a threat (e.g., an injury or a wound). However, the body’s ability to wind down the response after the threat has passed decreases as the body ages. This results in a consistent low-level, age-related inflammation known as “inflammaging” that is thought to weaken cells and tissues, including the brain. As aging is the greatest risk factor for Parkinson’s disease (PD), many have hypothesized that inflammaging plays a role in the development and progression of the disease. The details and mechanisms behind such a connection have remained a mystery, but Sarah Talley, PhD, recipient of a Parkinson’s Foundation Postdoctoral Fellowship for Basic Scientists, is hoping to shed some light on the subject.
Dr. Talley, working in the lab of Dr. Edward Campbell at the Loyola University Medical Center in Chicago, IL, seeks to understand how inflammaging may exacerbate the spread of alpha-synuclein clumps in the brain. These tangled-up alpha-synuclein proteins have been directly associated with PD, causing progressive neurodegeneration as they spread from cell to cell. It has also been shown that mice experience inflammaging like humans, making them the model of choice for Dr. Talley’s research.
What is inflammaging? Inflammaging refers to consistent inflammation that
increases as a person ages. It can weaken cells and tissues, including the brain, and may play a role in PD progression.
The key to these experiments is a genetically modified mouse line, previously generated by Dr. Talley and her fellow researchers, in which key cell types in the brain light up when experiencing inflammation. This light – bioluminescence, more specifically – can be measured and quantified under a high-powered microscope, allowing Dr. Talley to quantify inflammation in different brain cell types over time. With sophisticated cranial window imaging techniques, she will be able to make these measurements while the mice are still alive, providing valuable data over time.
Dr. Talley will inject alpha-synuclein tangles into the brains of these mice and monitor how those tangles spread and cause damage in the brain over time, but also how that spread affects brain-wide inflammation. By conducting these experiments in both young (6-week-old) and old (18-month-old) mice, Dr. Talley will be able to compare inflammation changes and alpha-synuclein spread between the age groups.
Dr. Talley, excited for the chance to start this research with the support of the Parkinson’s Foundation, spoke to the significance of this project: “We finally have the tools in place to measure when and where inflammation occurs in the [brain] during Parkinson's disease development in mouse models of the disease… These experiments will provide foundational knowledge that can inform on when and where anti-inflammatory therapeutics could be used to remedy disease in PD patients."
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