Detection of behavioral impairments correlated to neurochemical deficits in mice treated with moderate doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.
Overt behavioral symptoms of Parkinson's disease (PD) do not occur until over 80% of the striatal dopamine content has been lost. Diagnosis of the disorder relies on identifying clinical symptoms including akinesia, resting tremor, and rigidity. In retrospect, behavioral deficits are observed several years prior to diagnosis. Behavioral manifestations in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD, such as changes in general locomotor activity and rotorod performance, require large doses of MPTP and are often transient. We hypothesized that, as in PD, subtle behavioral changes also occur in the MPTP model. In this paper, we demonstrate that mice treated with moderate doses of the dopaminergic toxin MPTP display deficits in behavioral parameters that are significantly correlated with the loss of striatal dopamine. In addition, these behavioral measures are correlated to dopamine transporter, vesicular monoamine transporter, and tyrosine hydroxylase expression and are improved following L-DOPA administration. Detection of dopamine-modulated behavioral changes in moderately depleted MPTP mice will allow for more efficacious use of this model in PD research.
Tillerson
Jennifer L
JL
Institute for Neuroscience, University of Texas at Austin, Austin, TX 78712, USA.
Caudle
W Michael
WM
Reverón
Maria E
ME
Miller
Gary W
GW
D015102:3,4-Dihydroxyphenylacetic Acid / Q000032:analysis; D000367:Age Factors; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology; D001522:Behavior, Animal; D003342:Corpus Striatum / Q000737:chemistry; D004195:Disease Models, Animal; D004298:Dopamine / Q000032:analysis; D050483:Dopamine Plasma Membrane Transport Proteins; D005552:Forelimb / Q000502:physiology; D006719:Homovanillic Acid / Q000032:analysis; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D026901:Membrane Transport Proteins / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D020734:Parkinsonian Disorders / Q000175:diagnosis* / Q000188:drug therapy / Q000503:physiopathology*; D004856:Postural Balance; D020127:Recovery of Function; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins; D016138:Walking
D000978:Antiparkinson Agents; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins; D015102:3,4-Dihydroxyphenylacetic Acid; D007980:Levodopa; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine; D006719:Homovanillic Acid