Parkinson’s Disease and cell type by new and advance technique

A progressive condition that affects nerve cells in the brain responsible for body movement is Parkinson's disease (PD). Symptoms such as tremors, slowness, stiffness, and balance problems arise when dopamine-producing neurons die.

A new method for isolating a type of brain cell associated with the symptoms of Parkinson's disease has been developed by researchers at Carnegie Mellon University (CMU), allowing them to study that cell type in depth.

This paper publish in " in the journal JNeurosci under titled, “Cell type-specific oxidative stress genomic signatures in the globus pallidus of dopamine depleted mice.” 

                               

Despite the distinct roles these cell types perform in the neural network, due to the complexity of isolating unusual subtypes of neurons, the molecular correlates remain unclear. We developed a new purification strategy for viral affinity, Cre-Specific Nuclear Anchored Independent Labeling (cSNAIL), to isolate Cre recombinase-expressing (Cre+) nuclei from the adult mouse brain, the researchers wrote, to address this issue.

Andreas Pfenning, an assistant professor in the computational biology department of CMU, explained, "Even a tiny chunk of brain tissue may have hundreds of different cell types." "In the action of an animal and even in illness, each of these cell types has different functions." Thus, distinguishing cells of a certain type from their neighbours is a crucial first step for researchers who want to study them.

The researchers focused on neurons that are parvalbumin-expressing (PV+) and have been involved in Parkinson's disease.

A virus commonly used by researchers to deliver DNA to brain cells is used in the new method. Cre induces the tag to fluoresce when the virus enters PV+ cells. To detect the tag and pull the PV+ nuclei away from the others, the antibodies were then used.

Alyssa Lawler, PhD candidate at CMU, added, "The technique proved to be really specific, really effective," and noted that it can be adapted to other mouse models that use the Cre protein.

In other earlier aspects of Parkinson's disease, oxygen-sensing pathways have been involved, but not in PV+ cells before," Lawler said." Both protecting and killing cells during neurodegeneration are involved in these pathways.

They discovered evidence for upregulation of the oxygen homeostasis maintaining pathway involving Hif2a by applying this technology to GPe PV+ neurons in a mouse model of Parkinson's disease. These findings provide new insight into how neuron subtypes outside the substantia nigra pars compacta (SNpc) can compensate, according to the researchers, at the molecular level for differences in the neural circuit of motor production during the progression of Parkinson's disease.

The team noted that their study's datasets are part of a larger effort to build machine learning models that will help researchers interpret disease mechanisms by looking at how specific DNA sequences react across cell types to different conditions. Lawler said that they are learning how to speak with cells, to speak their language.

Part of the Parkinson's disease process develops as cells, particularly the crescent-shaped cell mass known as the substantia nigra, are destroyed in certain parts of the brain stem. In substantia nigra, nerve cells send fibres out to tissue located on both sides of the brain. There, essential neurotransmitters are released by the cells that help control movement and coordination. These findings provide new insight into how neuron subtypes outside of the substantia nigra can compensate for differences in the neural circuit of motor production during the progression of Parkinson's disease at the molecular level.