Hyper-Homocysteinemia Alters Amyloid Peptide-Clusterin Interactions and Neuroglial Network Morphology and Function in the Caudate After Intrastriatal Injection of Amyloid Peptides

Author(s): Giuseppina Leo , Susanna Genedani , Monica Filaferro , Chiara Carone , Norma Andreoli , Serenella Astancolle , Pierpaolo Davalli , Kjell Fuxe , Luigi F. Agnati .

Journal Name: Current Alzheimer Research

Volume 4 , Issue 3 , 2007

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Abstract:

Amyloid peptides (Aβ) are fragments of the Amyloid Precursor Protein (APP), an integral membrane protein. Aβ peptides are continuously generated by neurons and non-neuronal cells via sequential cleavage of APP by secretases. In particular, Aβ1-42 is the main component of the senile plaques associated with Alzheimers disease (AD). Glial cells participate in the uptake of soluble extra-cellular Aβ and in the clearance of this material at localized sites where the Aβ are concentrated. It has been shown that clusterin (Apo J) and apolipoprotein E (ApoE) exert important additive effects in reducing Aβ deposition. In agreement with the fact that homocysteine (Hcy) potentiates Aβ peptide neurotoxicity, and Hcy brain levels increase with age, it has been demonstrated that high plasma levels of Hcy are a risk factor for AD. In the present paper, we used animals subjected to chronic intake of methionine (1 g/kg/day) in the drinking water, since this treatment can increase plasma Hcy levels by 30%. By means of this animal model, interactions between the Aβ β- sheet rich fibrils and clusterin, have been evaluated in striata of animals after Aβ injection. Furthermore, it has been demonstrated that Aβ peptides are not only signals capable of activating astrocytes but also capable of reducing tyrosinehydroxylase immunoreactivity in the basal ganglia probably leading to a reduction of volume transmission. These alterations in the neuroglial network morphology and function can, at least in part, explain the enhanced pain threshold observed in the Aβ intra-striatally injected animals.

Keywords: Homocysteine, clusterin, β-amyloid, pain, neuroglial network, TH, GFAP, rat

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Article Details

VOLUME: 4
ISSUE: 3
Year: 2007
Page: [305 - 313]
Pages: 9
DOI: 10.2174/156720507781077223
Price: $58

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