July 24, 2024

New Study Sheds Light on the Progression of Neurodegenerative Disorders

A new study published in Aging Volume 15, Issue 21, “Longitudinal characterization of behavioral, morphological, and transcriptomic changes in a tauopathy mouse model,” delves into the mechanisms driving the progression of neurodegenerative disorders such as Alzheimer’s disease (AD).

Researchers from the State University of New York at Buffalo’s Jacobs School of Medicine and Biomedical Sciences, including Qing Cao, Manasa Kumar, Allea Frazier, Jamal B. Williams, Shengkai Zhao, and Zhen Yan, aimed to understand how brain dysfunction advances in neurodegenerative disorders.

To achieve this, they conducted a longitudinal study involving a tauopathy mouse model, specifically the P301S transgenic mice. The researchers examined behavioral, morphological, and transcriptomic changes over time.

The findings showed that P301S mice exhibited cognitive deficits as early as 3 months old. By 5-6 months, they also displayed deficits in social preference and social cognition. The study further revealed a significant decrease in arborization in the basal dendrites of hippocampal pyramidal neurons from 3 months, as well as apical dendrites of prefrontal cortex (PFC) pyramidal neurons at 9 months.

Transcriptomic analysis of genome-wide changes showed an enrichment of upregulated synaptic genes at 3 months. However, in the PFC and hippocampus of P301S mice at 9 months, most of these synaptic genes were downregulated. The time-dependent changes in gene expression could potentially lead to progressive alterations in neuronal structure and function, ultimately resulting in the manifestation of behavioral symptoms in tauopathies.

The longitudinal characterization of these behavioral, morphological, and transcriptomic changes in a tauopathy mouse model provides valuable insights into the mechanisms underlying the progression of AD and related neurodegenerative disorders. By manipulating key molecular players and conducting electrophysiological measurements of neuronal functions in future studies, researchers hope to identify early intervention strategies for these debilitating diseases.

Neurodegenerative disorders, including AD, have long been known to involve a gradual onset of neurobiological changes that precede clinical diagnosis by several decades. This study expands our understanding of the progression of such disorders and could open up avenues for developing targeted interventions in the early stages.

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