Persistent penetration of MPTP through the nasal route induces Parkinson's disease in mice.
The aetiology of idiopathic Parkinson's disease (PD) is poorly defined but environmental aggression may be relevant. Here, we report a new model of PD in mice, based on chronic inoculation with neurotoxins in the nasal cavity, which is a natural route of contact with the environment. C57BL/6 mice, submitted to daily intranasal inoculation with MPTP for 30 days, developed motor deficits that correlated with a progressive and severe depletion of striatal dopamine levels, and loss of tyrosine hydroxylase and dopamine transporter staining in substantia nigra and striatum. Moreover, mice intranasally inoculated with MPTP developed strong astrogliosis and microgliosis in substantia nigra and striatum. Consistent with these observations, a role for oxidant aggression was demonstrated by increased levels of Mn-superoxide dismutase. However, alpha-synuclein aggregation was not observed. This new animal model provides a new tool for studying PD symptoms that develop slowly over time, and it may be used to asses risk from environmental neurotoxins.
Rojo
Ana I
AI
Instituto de Investigaciones Biomédicas and Departamento de Bioquímica, Facultad de Medicina, Universidad Autónoma de Madrid, Arzobispo Morcillo 4, 28029 Madrid, Spain.
Montero
Celia
C
Salazar
María
M
Close
Ryan M
RM
Fernández-Ruiz
Javier
J
Sánchez-González
Miguel A
MA
de Sagarra
María Rosa
MR
Jackson-Lewis
Vernice
V
Cavada
Carmen
C
Cuadrado
Antonio
A
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000008:administration & dosage* / Q000378:metabolism; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000110:Acetylcholinesterase / Q000378:metabolism; D000281:Administration, Intranasal; D000818:Animals; D001522:Behavior, Animal; D015153:Blotting, Western / Q000379:methods; D001921:Brain / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009498:Neurotoxins / Q000008:administration & dosage* / Q000378:metabolism; D010300:Parkinson Disease / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D051843:Synucleins / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism
D009419:Nerve Tissue Proteins; D009498:Neurotoxins; D012333:RNA, Messenger; D051843:Synucleins; D015102:3,4-Dihydroxyphenylacetic Acid; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase; D000110:Acetylcholinesterase; D004298:Dopamine