Intrastriatal infusion of the Parkinsonian neurotoxin, MPP(+), induces damage of striatal cell nuclei in Sprague-Dawley rats.
The potent Parkinsonian neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine is known to destroy dopaminergic neurons of the basal ganglia. Its neurotoxically active metabolite, 1-methyl-4-phenyl pyridinium (MPP(+)), has been examined in the present study to verify whether administration of the neurotoxin that depletes about 70% of the striatal dopamine (DA) can cause damage to nuclear components of the cells at the terminal region, the striatum. Unilateral intrastriatal infusion of MPP(+) (100 and 200 nmol in 4 microl saline) caused a dose-dependent depletion of striatal DA (69 and 92%, respectively), as measured employing HPLC electrochemistry. It also resulted in the loss of tyrosine hydroxylase (TH) immunoreactivity in the striatum and in the perikarya at substantia nigra pars compacta (SNpc) and acetylcholinesterase histoenzymological staining in the striatum. Specific nuclear staining employing Hoechst 33342 and acridine orange revealed distorted and spindle shaped nuclei, and perinuclear positioning of nucleolus, respectively, for the former and latter dyes in several of the cell populations in the ipsilateral striatum compared to the contralateral side. Existence of a widened lateral ventricle at the side that received the neurotoxin, as well as denser cellular population, as compared to the contralateral side under transmission electron microscope evidenced general shrinkage of the striatum. Extensive damage of the nuclei was visible in the cell bodies in the treated side. These results demonstrate non-specific damage extending to the cellular groups including cholinergic neurons in addition to dopaminergic neurons in the striatum to intrastriatal administration of the Parkinsonian neurotoxin, MPP(+).
Banerjee
Rebecca
R
Division of Clinical and Experimental Neuroscience, Indian Institute of Chemical Biology, 4 Raja S.C. Mullick Road, Jadavpur, Kolkata 700032, West Bengal, India.
Sreetama
Sen
S
Saravanan
Karuppagounder S
KS
Chandra
Goutam
G
Nath De
Sailendra
S
Mohanakumar
Kochupurackal P
KP
D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001284:Atrophy / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D002467:Cell Nucleus / Q000187:drug effects* / Q000473:pathology; D002799:Cholinergic Fibers / Q000187:drug effects / Q000473:pathology; D004396:Coloring Agents; D003342:Corpus Striatum / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D006540:Herbicides / Q000633:toxicity; D008297:Male; D046529:Microscopy, Electron, Transmission; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D009498:Neurotoxins / Q000633:toxicity; D020734:Parkinsonian Disorders / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014446:Tyrosine 3-Monooxygenase / Q000187:drug effects / Q000378:metabolism
D004396:Coloring Agents; D006540:Herbicides; D009498:Neurotoxins; D014446:Tyrosine 3-Monooxygenase; D000109:Acetylcholine; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine