Effects of lipids and aging on the neurotoxicity and neuronal loss caused by intracerebral injections of the amyloid-beta peptide in the rat.
The influence of diet and age on the area of lesion and on the neuronal density in the cerebral cortex was studied in rats following local injections of the amyloid-beta peptide (Abeta1-40) in PBS vehicle into the left frontal and cingulate cortices and compared with effects of injections of PBS alone into the corresponding regions of the right hemisphere The experiments were carried out 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 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. The results showed that the greatest area of lesion was at Abeta injection sites in the high-cholesterol fed group of aged animals. The results also revealed a significant variance in the neuronal density by group and by injection type. Thus, high-cholesterol fed animals showed a greater reduction in neuronal density at Abeta and PBS-injected sites than that seen in the high-fat or control groups. The results also indicate that the loss of neurons at the Abeta injection site exceeds that seen in the PBS-injected area. The greatest reduction in the neuronal density was found at Abeta-injected site in the high-cholesterol fed group of aged animals. In conclusion, our findings indicate an interaction between lipids, age, and Abeta neurotoxicity, and might provide insights into the basic mechanisms involved in a short-term (acute-to-subchronic) response to Abeta peptide.
Gonzalo-Ruiz
A
A
Laboratory of Neuroanatomy, Institute of Neuroscience of Castilla and León, Valladolid University, Nicolas Rabal Street, 17, 42003-Soria, Spain. agruiz@ah.uva.es
Pérez
J L
JL
Sanz
J M
JM
Geula
C
C
Arévalo
J
J
D000375:Aging / Q000502:physiology*; D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D001921:Brain; D002540:Cerebral Cortex / Q000473:pathology; D002791:Cholesterol, Dietary / Q000633:toxicity; D004032:Diet; D004041:Dietary Fats / Q000633:toxicity; D006651:Histocytochemistry; D007267:Injections; D008055:Lipids / Q000097:blood / Q000502:physiology*; D009454:Neurofibrils / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000473:pathology*; D020258:Neurotoxicity Syndromes / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D012307:Risk Factors; D016707:Tissue Fixation
D016229:Amyloid beta-Peptides; D002791:Cholesterol, Dietary; D004041:Dietary Fats; D008055:Lipids