P2.28. NEUROPROTECTIVE ROLE OF VOLUNTARY PHYSICAL ACTIVITY IN MICE C57BL/6 EXPOSED TO METHAMPHETAMINE
Magdalena Dębiec1,3, Marta Nowacka-Chmielewska1, Mateusz Smolarz1,4, Katarzyna Bogus2, Jarosław Barski3, Andrzej Małecki1, Michal Toborek1,5
1 Laboratory of Molecular Biology, Institute of Physiotherapy and Health Sciences, Academy of Physical Education, Katowice, Poland
2 Department of Histology, Faculty of Medical Sciences in Katowice, Medical University of Silesia, Katowice, Poland
3 Department of Physiology, Faculty of Medical Sciences in Katowice, Medical University of Silesia, Katowice, Poland
4 Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice, Poland
5 University of Miami Miller School of Medicine, Department of Biochemistry and Molecular Biology, Miami, FL, USA
INTRODUCTION: Methamphetamine (METH) is a potent psychoactive agent that affects the central nervous system, mainly by increasing neurotransmitter levels such as dopamine, norepinephrine and serotonin. Long-term use results in cognitive deficits and memory impairment.
AIM(S): The study aimed to test the hypothesis that voluntary exercise protects against METH-induced neurotoxicity and neurogenesis disruption in adult female and male mice.
METHOD(S): 10-week-old C57BL/6 mice, both male and female, were used in the experiment. Within each sex, mice were divided into two groups - METH and Saline (Veh). Mice received an injection three times a day, for five days, in 4-hour intervals. METH was administered according to an ascending dosage schedule (0.2 - 2.4 mg/kg), using increments of 0.2 mg/kg with each injection for 4 days. On the last day, mice were given METH in three doses of 4.0 mg/kg. Mice from the control group were injected with saline. After the injection procedure, mice were subjected to voluntary wheel running for 14 consecutive days, followed by behavioral tests measuring locomotor activity (Open Field Test), cognitive ability (New Object Recognition Test), and spatial learning (Morris Water Maze). Mouse brain slides were prepared from the hippocampal area and then analyzed by immunofluorescence.
RESULTS: METH induced impaired neurogenesis, and led to distruption of cognitive functions in mice, with a noticeable sex-related difference in the response to METH toxicity. Physically active mice showed less neuronal damage and better performance in cognitive tests than the sedentary ones. In running mice, increased neurogenesis was observed in the hippocampus, which was correlated with an improvement in memory and cognitive function.
CONCLUSIONS: METH primarily increases physical activity, nevertheless, in the long term leads to neuronal damage and cognitive deficits in mice. Our results indicate that humans addicted to METH may benefit from appropriate physical activity protocols.
FINANCIAL SUPPORT: Research funded by the National Science Center, Poland, grant no. 2019/33/B/NZ4/02721.