Bilateral Injections of Amyloid-β 25-35 into the Amygdala of Young Fischer Rats: Behavioral, Neurochemical, and Time Dependent Histopathological Effects

To examine the time course of the histopathological effects of bilateral injections of amyloid-β 25-35 (Aβ) and to determine if these effects are associated with a reduction in choline acetyltransferase activity and behavioral impairments, we injected Aβ (5.0 nmol) into the amygdala of young male Fischer rats. Control rats received vehicle infusions. For histological analysis, animals were sacrificed at 8, 32, 64, 96, and 128 days postoperatively (n = 21–33 per timepoint). Aβ induced neuronal tau-2 staining in the right, but not the left amygdala and hippocampus. Aβ also induced reactive astrocytosis and neuronal shrinkage within the right hippocampus and amygdala, respectively. As with tau-2, these same brain regions within the left hemisphere in the Aβ-treated rats were significantly less affected. In addition, Aβ appeared to induce microglial and neuronal interleukin-1β staining. The histopathological effects of Aβ peaked at 32 days postoperatively but were not associated with a reduction in amygdaloid choline acetyltransferase activity. In a separate experiment, behavioral effects of bilateral intra-amygdaloid injections of Aβ were analyzed at 34–52 days postoperatively. In an open field test, the treatment groups differed only in the numbers of rears emitted (p = 0.016). There was no effect of Aβ in the Morris water maze or in the acquisition and retention of a one-way conditioned avoidance response. These data suggest a laterality in the histopathological effects of Aβ and that the effects of single injections are in part transient. These findings also suggest a direct association between plaque and tangle formation in Alzheimer’s disease, and support the use of this rat model to screen drugs that may alter the initial pathological events associated with Alzheimer’s disease, that occur before the manifestations of extensive behavioral impairments become evident.