Mitochondrial Dysfunction Appears in the Hippocampal Neurons of 3-Month-Old Alpha-Synuclein Transgenic Mice

Author(s): Zegang Ma, Shang Liu

Alpha-synuclein A53T transgenic mouse (A53T) is an essential tool to investigate the onsets and the extents of Parkinson’s disease (PD) non-motor symptoms. Previous studies showed A53T mice exhibit a number of non-motor symptoms. However, the cause for these non-motor symptoms is still unknown. Our aim is to investigate the mitochondrial function in the hippocampal neurons of 3-month-old A53T mice. By enzyme-linked immunosorbent assay, we showed that the reactive oxidative species (ROS) level significantly increased in the hippocampus of A53T mice compared with that of the littermate controls. The cytochrome C content in the hippocampus of the A53T mice also increased. In addition, the ATP content decreased in the hippocampus of the A53T mice compared with the control. These results indicate that mitochondrial dysfunction appears in the hippocampal neurons of A53T mice, which may contribute to the cognitive disturbence in the young A53T mice.

Parkinson's disease, A53T, Non-Motor Symptoms, Mitochondrial Dysfunction

1. Arvanitakis, Z., Wilson Rs Fau - Bienias, J. L., Bienias Jl Fau - Bennett, D. A., Bennett, D. A., 2007. Diabetes and parkinsonian signs in older persons. Alzheimer Dis Assoc Disord 21, 144-149.
2. Bergamini, C., Moruzzi, N., Volta, F., Faccioli, L., Gerdes, J., Mondardini, M. C., Fato, R., 2016. Role of mitochondrial complex I and protective effect of CoQ10 supplementation in propofol induced cytotoxicity. J Bioenerg Biomembr 48, 413-423.
3. Charles, M., Ejskjaer N Fau - Witte, D. R., Witte Dr Fau - Borch-Johnsen, K., Borch-Johnsen K Fau - Lauritzen, T., Lauritzen T Fau - Sandbaek, A., Sandbaek, A., 2011. Prevalence of neuropathy and peripheral arterial disease and the impact of treatment in people with screen-detected type 2 diabetes: the ADDITION-Denmark study. Diabetes Care 34, 2244-2249.
4. Choi, W. S., Kim, H. W., Tronche, F., Palmiter, R. D., Storm, D. R., Xia, Z., 2017. Conditional deletion of Ndufs4 in dopaminergic neurons promotes Parkinson's disease-like non-motor symptoms without loss of dopamine neurons. Sci Rep 22.
5. Erro, R., Santangelo G Fau - Picillo, M., Picillo M Fau - Vitale, C., Vitale C Fau - Amboni, M., Amboni M Fau - Longo, K., Longo K Fau - Costagliola, A., Costagliola A Fau - Pellecchia, M. T., Pellecchia Mt Fau - Allocca, R., Allocca R Fau - De Rosa, A., De Rosa A Fau - De Michele, G., De Michele G Fau - Santoro, L., Santoro L Fau - Barone, P., Barone, P., 2012. Link between non-motor symptoms and cognitive dysfunctions in de novo, drug-naive PD patients. J Neurol 259, 1808-1803.
6. Grinberg, L. T., Rueb U Fau - Alho, A. T. d. L., Alho At Fau - Heinsen, H., Heinsen, H., 2010. Brainstem pathology and non-motor symptoms in PD. J Neurol Sci 289, 81-88.
7. Hely, M. A., Morris Jg Fau - Reid, W. G. J., Reid Wg Fau - Trafficante, R., Trafficante, R., 2005. Sydney Multicenter Study of Parkinson's disease: non-L-dopa-responsive problems dominate at 15 years. Mov Disord 20, 190-199.
8. Imai, Y., Lu, B., 2011. Mitochondrial dynamics and mitophagy in Parkinson's disease: disordered cellular power plant becomes a big deal in a major movement disorder. Curr Opin Neurobiol 21, 935-941.
9. Irvine, G. B., El-Agnaf Om Fau - Shankar, G. M., Shankar Gm Fau - Walsh, D. M., Walsh, D. M., 2008. Protein aggregation in the brain: the molecular basis for Alzheimer's and Parkinson's diseases. Mol Med 14, 451-464.
10. Jurado-Coronel, J. C., Cabezas, R., Avila Rodriguez, M. F., Echeverria, V., Garcia-Segura, L. M., Barreto, G. E., 2017. Sex differences in Parkinson's disease: Features on clinical symptoms, treatment outcome, sexual hormones and genetics. . Front Neuroendocrinol.
11. Kohl, Z., Winner B Fau - Ubhi, K., Ubhi K Fau - Rockenstein, E., Rockenstein E Fau - Mante, M., Mante M Fau - Munch, M., Munch M Fau - Barlow, C., Barlow C Fau - Carter, T., Carter T Fau - Masliah, E., Masliah E Fau - Winkler, J., Winkler, J., 2012. Fluoxetine rescues impaired hippocampal neurogenesis in a transgenic A53T synuclein mouse model. Eur J Neurosci 35, 10-19.
12. Marinus, J., van Hilten, J. J., 2015. The significance of motor (a)symmetry in Parkinson's disease. Mov Disord 30, 379-385.
13. Mehndiratta, M., Garg Rk Fau - Pandey, S., Pandey, S., 2011. Nonmotor symptom complex of Parkinson's disease--an under-recognized entity. J Assoc Physicians India 59, 302-308.
14. Muller, T., Buttner T Fau - Gholipour, A. F., Gholipour Af Fau - Kuhn, W., Kuhn, W., 2003. Coenzyme Q10 supplementation provides mild symptomatic benefit in patients with Parkinson's disease. Neurosci Lett 341, 201-204.
15. Ozansoy, M., Basak, A. N., 2013. The central theme of Parkinson's disease: alpha-synuclein. Mol Neurobiol 47, 460-465.
16. Ozdilek, B., Gunal, D. I., 2012. Motor and non-motor symptoms in Turkish patients with Parkinson's disease affecting family caregiver burden and quality of life. J Neuropsychiatry Clin Neurosci 24, 478-483.
17. Schaeffer, E., Berg, D., 2017. Dopaminergic Therapies for Non-motor Symptoms in Parkinson's Disease. CNS Drugs 31, 551-579.
18. Willison, L. D., Kudo T Fau - Loh, D. H., Loh Dh Fau - Kuljis, D., Kuljis D Fau - Colwell, C. S., Colwell, C. S., 2013. Circadian dysfunction may be a key component of the non-motor symptoms of Parkinson's disease: insights from a transgenic mouse model. Exp Neurol 243, 57-66.