MODIFICATION OF EXPERIMENTAL ROTENONE MODEL OF PARKINSON’S DISEASE
L.P. Voitenko, A.G. Nikonenko
O.O.Bogomoletz Institute of Physiology of National
Academy of Sciences of Ukraine, Kyiv
DOI: https://doi.org/10.15407/fz61.01.083
Abstract
A modification of experimental model of Parkinson’s disease
is proposed presuming the stereotaxic infusion of rotenone
solution using a special device into the cental part of substantia
nigra (SN) pars compacta of adult Wistar rats. It was shown
that 10 days after infusion of the neurotoxin the density
of dopaminergic (DA) neurons in the infusion area drops
nearly six-fold, to 20.2±3.2 neurons/mm2, with respect to
the corresponding value in non-affected controlateral SN,
119.0±3.3 neurons/mm2. Electron microscopy has shown
ultrastructural impairments in mitochondria of SN neurons in the
infusion area displayed mainly as a cristae disarray. The absence
of overall toxicity and selectivity of the brain tissue impairments
provide an evidence that the proposed rotenone model
modification is adequate and can be used to study the effects of
DA neuronal degeneration typical of Parkinson’s disease.
Keywords:
rotenone; in vivo model; Parkinson’s disease.
References
- Roeper J. Dissecting the diversity of midbrain dopamine neurons. Trends Neurosci. 2013; 36(6): 336-42.
CrossRef
PubMed
- Abeliovich A, Schmitz Y, Farinas I, Choi-Lundberg D, Ho WH, Castillo PE, Shinsky N, Verdugo JM, Armanini M, Ryan A, Hynes M, Phillips H, Sulzer D, Rosenthal A. Mice lacking alpha-synuclein display functional deficits in the nigrostriatal dopamine system. Neuron. 2000; 25(1): 239-52.
CrossRef
- Tkachenko MN, Zozulya IS, Shapoval MV, Sagach VF. Parkinsonism: current concepts of pathogenesis and the possible ways to correct. Ukr Med J. 2000; 3: 9-14.
- Ungerstedt U. Striatal dopamine release after amphetamine or nerve degeneration revealed by rotational behaviour. Acta Physiol Scand Suppl. 1971; 367: 49-68.
CrossRef
PubMed
- Bloem BR, Irwin I, Buruma OJ, Haan J, Roos RA, Tetrud JW, Langston JW. The MPTP model: versatile contributions to the treatment of idiopathic Parkinson's disease. J Neurol Sci. 1990; 97(2-3): 273-93.
- Bove J, Perier C. Neurotoxin-based models of Parkinson's disease. Neuroscience. 2012; 211: 51-76.
CrossRef
PubMed
- Alam M, Schmidt WJ. L-DOPA reverses the hypokinetic behaviour and rigidity in rotenone-treated rats. Behav Brain Res. 2004; 153(2): 439-46.
CrossRef
PubMed
- Cannon JR, Tapias V, Na HM, Honick AS, Drolet RE, Greenamyre JT. A highly reproducible rotenone model of Parkinson's disease. Neurobiol Dis. 2009; 34(2): 279-90.
CrossRef
PubMed PubMedCentral
- Dickman KG, Mandel LJ. Differential effects of respiratory inhibitors on glycolysis in proximal tubules. Am J Physiol. 1990; 258(6): 1608-15.
- Betarbet R, Sherer TB, MacKenzie G, Garcia-Osuna M, Panov AV, Greenamyre JT. Chronic systemic pesticide exposure reproduces features of Parkinson's disease. Nat Neurosci. 2000; 3(12): 1301-06.
CrossRef
PubMed
- Borland MK, Trimmer PA, Rubinstein JD, Keeney PM, Mohanakumar K, Liu L, Bennett JP Jr. Chronic, low-dose rotenone reproduces Lewy neurites found in early stages of Parkinson's disease, reduces mitochondrial movement and slowly kills differentiated SH-SY5Y neural cells. Mol Neurodegener. 2008; 3: 21.
CrossRef
PubMed PubMedCentral
- Keeney PM, Xie J, Capaldi RA, Bennett JP Jr. Parkinson's disease brain mitochondrial complex I has oxidatively damaged subunits and is functionally impaired and misassembled. J Neurosci. 2006; 26(19): 5256-64.
CrossRef
PubMed
- Ferrante RJ, Schulz JB, Kowall NW, Beal MF. Systemic administration of rotenone produces selective damage in the striatum and globus pallidus, but not in the substantia nigra. Brain Res. 1997; 753(1): 157-62.
CrossRef
- Xiong N, Huang J, Zhang Z, Zhang Z, Xiong J, Liu X, Jia M, Wang F, Chen C, Cao X, Liang Z, Sun S, Lin Z, Wang T. Stereotaxical infusion of rotenone: a reliable rodent model for Parkinson's disease. PLoS One. 2009; 4(11): e7878.
- Paxinos G, Watson Ch. The rat brain in stereotaxic coordinates. New York: Academic Press. 2006: 456 p.
- Itoh K, Nakamura K, Iijima M, Sesaki H. Mitochondrial dynamics in neurodegeneration. Trends Cell Biol. 2013; 23(2): 64-71.
CrossRef
PubMed PubMedCentral
- Goedert M, Jakes R, Crowther RA, Spillantini MG. Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy as α-synucleinopathies. Methods Mol Med. 2001; 62: 33-59.
CrossRef
|