Evaluation of the effects of apocynine on spatial learning, balance and memory function in an experimental model of alzheimer disease

Scope: The aim of this study is the evaluation of the therapeutic effect of intraperitoneal apocynine application in an experimental model of Alzheimer disease. The model is realized by intracerebroventricular STZ injection and the treatment is evaluated by focusuing on spatial learning, balance and memory function. The reference investigations are water-maze, rota-rod, accelerod tests, MDA-GSH levels of neural tissue, routine blood biochemistry and histopathology by hematoxilen-eosin and transmission electron microscopy Material and Method: The study involved a total of 70 Wistar-Albino rats ( 35 males and 35 females ) weighing 200-275 gr each. 3 mg/kg STZ dissolved in 20 microliters of artificial CSF is applied to 50 rats via stereotactic route in a single session. Only artificial CSF of the same volume is injected to 20 rats stereotactically as control. 34 rats from the STZ group and 16 rats from the control group survived for twenty-one days after the first application. They are evaluated by water maze, rota-rod and accelerod tests. 15 rats with test results suitable for experimental Alzheimer disease made up the treatment and 14 rats the control group. Treatment and control groups were randomly divided into two groups. One of the subgroups from each received 10 mg/kg intraperitoneal apocynine injection while the other had isotonic saline injection with the same volume. After the interventional procedure, water maze, rota-rod and accelerod tests were repeated. Then rats were sacrificed and routine blood biochemistry parameters were studied. Brain is extracted with no extra damage and the two hemispheres were seperated. MDA-GSH analyses were performed from one hemisphere, while the other hemisphere was spared for histopathological investigation. Results: On pretreatment group, significant difference between the experimental Alzheimer disease and the control groups was remarked. Rota-rod tests with 5 rpm, 10 rpm, 20 rpm, 30 rpm, 40 rpm and 4 minute accelerod test revealed significant difference within these groups. There is also significant difference related to the Alzheimer disease group without apocynine administration in the tests with 30-40 rpm. For pretreatment, there is significant difference in the arrival period to the platform in favor of control group in water maze tests. No difference was detected between the groups in posttreatment. The routine biochemical analysis from blood and GSH analysis from brain parenchyma revealed no significance. MDA analysis in neural tissue was significant. Hematoxylin-eosin staining and TEM histopathological results disclosed significant results in favor of apocynine treatment group. Control groups lack these histopathological findings. Conclusion: This study proves that the experimental model involving stereotactic ICV STZ administration for Alzheimer disease is relevant and the oxidative stress performed by these means is applicable. Brain injury performed by this technique is effectively managed by apocynine administration. This is confirmed by water maze, rota-rod and accelerod tests, histopathological and biochemical investigation. It is probable that apocynine administration for Alzheimer disease may be an effective and feasible alternative therapy method if it is supported by further investigations.