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

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

International journal of molecular sciences (2024-03-28)
Francesca Biagioni, Michela Ferrucci, Gloria Lazzeri, Mariarosaria Scioli, Alessandro Frati, Stefano Puglisi-Allegra, Francesco Fornai
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Dopamine β Hydroxylase Antibody, clone 4F10.2, ascites fluid, clone 4F10.2, Chemicon®
Sigma-Aldrich
Anti-Synuclein antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Anti-β-Actin antibody, Mouse monoclonal, clone AC-15, purified from hybridoma cell culture