Amyloid beta peptide-induced cholinergic fibres loss in the cerebral cortex of the rat is modified by diet high in lipids and by age.
The influence of diet and age on the effects of intracerebral injection of beta-amyloid peptide (Abeta1-40) in vehicle phosphate-buffered saline (PBS) and on the effects of vehicle alone on cholinergic fibres of the cerebral cortex was studied in rats. The experiments were carried in two groups of animals: one group of young adult rats and a second group of aged rats. Each group of animals, depending on the diet received, was divided into high-cholesterol, high-fat, and a control diet group. In order to evaluate the interaction of Abeta/PBS-cholesterol and of Abeta/PBS-fat, animals without dietary manipulation receiving Abeta and PBS injection were used as controls. High-cholesterol fed animals showed a statistically significant reduction of 49.62% in the number of cholinergic fibres at the Abeta injection site as compared with that at PBS injection site, while the high-fat and control animals showed a significant reduction of 28.13 and 26.81%, respectively. In all diet groups, the loss of cholinergic fibres caused by Abeta as compared to that caused by PBS injection was significantly greater in aged rats in comparison with that observed in the young animals. Furthermore, the results of a multivariate linear regression model revealed that the greatest reduction in cholinergic fibres was in the high-cholesterol fed animals (35 fibres/mm) as compared with that seen in the high-fat and control animals. A significantly greater reduction was also observed at Abeta injection site (28 fibres/mm) as compared with that caused by PBS injection, and a reduction of 16 cholinergic fibres per mm was found in aged animals as compared to that seen in young adult rats. These results show that high-cholesterol diet enhances the toxicity of Abeta peptide and that this is also age-dependent. Therefore, this study increases the evidences of the role of cholesterol in the pathology of Alzheimer's disease (AD).
Gonzalo-Ruiz
A
A
Laboratory of Neuroanatomy, Institute of Neuroscience of Castilla and León, Valladolid University, C/Nicolas Rabal Street, 17, 42003 Soria, Spain. agruiz@ah.uva.es
Sanz
J M
JM
Arévalo
J
J
Geula
C
C
Gonzalo
P
P
D000375:Aging / Q000187:drug effects* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000008:administration & dosage*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000473:pathology; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D002799:Cholinergic Fibers / Q000187:drug effects* / Q000473:pathology; D004041:Dietary Fats / Q000008:administration & dosage*; D010446:Peptide Fragments / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar
D016229:Amyloid beta-Peptides; D002791:Cholesterol, Dietary; D004041:Dietary Fats; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40)