Effects of lipids and aging on the neurotoxicity and neuronal loss caused by intracerebral injections of the amyloid-β 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-β peptide (Aβ1-40) 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 Aβ/PBS-cholesterol and of Aβ/PBS-fat, animals without dietary manipulation receiving Aβ and PBS injection were used as controls. The results showed that the greatest area of lesion was at Aβ 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 Aβ 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 Aβ injection site exceeds that seen in the PBS-injected area. The greatest reduction in the neuronal density was found at Aβ-injected site in the high-cholesterol fed group of aged animals. In conclusion, our findings indicate an interaction between lipids, age, and Aβ neurotoxicity, and might provide insights into the basic mechanisms involved in a short-term (acute-to-subchronic) response to Aβ peptide.