# Damage to the Locus Coeruleus Alters the Expression of Key Proteins in Limbic Neurodegeneration

## TL;DR

This study shows that damage to the locus coeruleus disrupts key proteins in brain regions linked to Alzheimer's and Parkinson's diseases.

## Contribution

The study demonstrates how locus coeruleus damage alters alpha-synuclein and Tau proteins in limbic regions, linking it to neurodegeneration.

## Key findings

- Damage to LC-NE axons increases alpha-synuclein and phospho-Tau in the hippocampus and piriform cortex.
- LC-NE damage decreases HSP70 and p62 expression in these regions.
- Findings suggest LC-NE loss may contribute to limbic neurodegeneration in AD and PD.

## Abstract

The present investigation was designed based on the evidence that, in neurodegenerative disorders, such as Alzheimer’s dementia (AD) and Parkinson’s disease (PD), damage to the locus coeruleus (LC) arising norepinephrine (NE) axons (LC-NE) is documented and hypothesized to foster the onset and progression of neurodegeneration within target regions. Specifically, the present experiments were designed to assess whether selective damage to LC-NE axons may alter key proteins involved in neurodegeneration within specific limbic regions, such as the hippocampus and piriform cortex, compared with the dorsal striatum. To achieve this, a loss of LC-NE axons was induced by the neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4) in C57 Black mice, as assessed by a loss of NE and dopamine-beta-hydroxylase within target regions. In these experimental conditions, the amount of alpha-synuclein (alpha-syn) protein levels were increased along with alpha-syn expressing neurons within the hippocampus and piriform cortex. Similar findings were obtained concerning phospho-Tau immunoblotting. In contrast, a decrease in inducible HSP70-expressing neurons and a loss of sequestosome (p62)-expressing cells, along with a loss of these proteins at immunoblotting, were reported. The present data provide further evidence to understand why a loss of LC-NE axons may foster limbic neurodegeneration in AD and limbic engagement during PD.