Results of a new cognitive method in rats on the Morris water maze used in modeling experimental Alzheimer's disease

Background

In Alzheimer's disease (AD) the loss of neurons in the hippocampal CA3 regions is present. In rats treated by sodium azide (NaN3) via subcutaneously implanted osmotic minipumps number of CA3 cells were decreased [1]. We developed a new method to produce AD-like dementia using single intracerebrally (ic.) injected NaN3 in rats.

Materials and methods

The CA3 neurons were chemically lesioned by intracerebrally administration of NaN3 in doses of 8 and 16 mg/ml. To examine learning functions Morris maze was used. During acquisition trials animals had to find a black platform within 120 s. We measured the "escape latency"(msec). Detailed histopathology of brain was performed at the termination of the study. Learning function was measured after 7 days of ic. treatment.

Results

8 and 16 mg/ml doses of NaN3 significantly decreased escape time in ic. NaN3 treated rats compared to control animals. Neuronal necrosis, shrunk neurons, neurofibrillary tangle-like structures were seen in hippocampal area, also.

Conclusions

Decreased learning capability was induced by the ic. injection of 8 mg/ml and 16 mg/ml NaN3 dose in rats. We proved that with the new method, acut ic. injection of NaN3 produces comparable level of dementia caused by 31 days infusion of NaN3 using implanted osmotic minipumps [2], and it seems to be suitable to produce dementia in rats.