title: Differential effects of intrastriatal 6-hydroxydopamine on cell number and morphology in midbrain dopaminergic subregions of the rat.
abstract: The midbrain dopaminergic perikarya are differentially affected in Parkinson׳s disease (PD). This study compared the effects of a partial unilateral intrastriatal 6-hydroxydopamine (6-OHDA) lesion model of PD on the number, morphology, and nucleolar volume of dopaminergic cells in the substantia nigra pars compacta (SNpc), ventral tegmental area (VTA), and retrorubral field (RRF). Adult, male rats (n=10) underwent unilateral intrastriatal infusion of 6-OHDA (12.5μg). Lesions were verified by amphetamine-stimulated rotation 7 days post-infusion. Rats were euthanized 14 days after treatment with 6-OHDA and brains were stained with a tyrosine hydroxylase-silver nucleolar (TH-AgNOR) stain. Dopaminergic cell number and morphology in the lesioned and intact hemispheres were quantified using stereological methods. The magnitude of decrease in planimetric volume, neuronal number, cell density, and neuronal volume resulting from 6-OHDA lesion differed between regions, with the SNpc exhibiting the greatest loss of neurons (46%), but the smallest decrease in neuronal volume (13%). The lesion also resulted in a decrease in nucleolar volume that was similar in all three regions (22-26%). These findings indicate that intrastriatal 6-OHDA lesion differentially affects dopaminergic neurons in the SNpc, VTA, and RRF; however, the resulting changes in nucleolar morphology suggest a similar cellular response to the toxin in all three cell populations.
authors.affiliation: Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Mail Stop 1018, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA. Electronic address: mstoffel@kumc.edu.
authors.forename: Michelle
authors.initials: M
authors.lastname: Healy-Stoffel
authors.affiliation: Department of Occupational Therapy, Doisy College of Health Sciences, St. Louis University, 3401 Caroline Street, St. Louis, MO 63104, USA. Electronic address: sahmad13@slu.edu.
authors.forename: S
authors.initials: S
authors.lastname: Omar Ahmad
authors.affiliation: Department of Molecular and Integrative Physiology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA. Electronic address: jstanford@kumc.edu.
authors.forename: John A
authors.initials: JA
authors.lastname: Stanford
authors.affiliation: Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Mail Stop 1018, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA. Electronic address: blevant@kumc.edu.
authors.forename: Beth
authors.initials: B
authors.lastname: Levant
mesh_terms: D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D002452:Cell Count; D002466:Cell Nucleolus / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D048430:Cell Shape; D048429:Cell Size; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D059290:Dopaminergic Neurons / Q000473:pathology*; D007839:Functional Laterality; D008297:Male; D008636:Mesencephalon / Q000187:drug effects* / Q000473:pathology* / Q000503:physiopathology; D009043:Motor Activity / Q000187:drug effects; D016627:Oxidopamine / Q000633:toxicity*; D020734:Parkinsonian Disorders / Q000473:pathology* / Q000503:physiopathology; D065842:Pars Compacta / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D018030:Silver Compounds; D014446:Tyrosine 3-Monooxygenase; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology
chemical_list: D000697:Central Nervous System Stimulants; D018030:Silver Compounds; D016627:Oxidopamine; D000661:Amphetamine; D014446:Tyrosine 3-Monooxygenase
keywords: 6-hydroxydopamine; Dopamine; Retrorubral field; Stereology; Substantia nigra; Ventral tegmental area