title: On the altered expression of tyrosine hydroxylase and calbindin-D 28kD immunoreactivities and viability of neurons in the ventral tegmental area of Tsai following injections of 6-hydroxydopamine in the medial forebrain bundle in the rat.
abstract: Calbindin-D 28kD is a calcium binding protein reported to protect neurons from degeneration by buffering intracellular calcium. It is expressed in midbrain dopaminergic neurons reported to be relatively resistant to degeneration in Parkinson's disease and certain of its animal models. Lesions of the nigrostriatal pathway produced in rats following injection of 6-hydroxydopamine result in a neurochemical profile similar to that seen in patients with Parkinson's disease. In the present study, brains were processed to exhibit tyrosine hydroxylase- and calbindin-D 28kD immunoreactivities in sections through the ventral mesencephalon at 3, 7, 10, 14 and 21 days after 6-hydroxydopamine had been injected into the medial forebrain bundle. Numbers of ventral mesencephalic calbindin-D 28kD immunoreactive neurons were significantly reduced ipsilateral to the lesions at 3 days post-lesion and, following slight recovery, remained significantly depleted through post-lesion day 21. The densities of calbindin-D 28kD and tyrosine hydroxylase immunoreactive neurons were different only at the 3 day post-lesion time point, when the apparent loss of calbindin-D 28 kD immunoreactive profiles was significantly greater. A lesion-induced increase in the proportion of neurons exhibiting both calbindin-D 28kD and tyrosine hydroxylase immunoreactivities, expected if calbindin-D 28kD is neuroprotective, was observed in the substantia nigra, pars compacta, but not in the ventral tegmental area. It is concluded that, while the observed losses of tyrosine hydroxylase and calbindin-D 28kD immunoreactivities do not necessarily reflect neuronal degeneration, they are not consistent with CB confering a neuroprotective advantage in the ventral tegmental area following 6-OHDA lesions as administered in this study.
authors.affiliation: Department of Anatomy and Neurobiology, School of Medicine, Saint Louis University, 1402 S. Grand Blvd., Saint Louis, MO 63104, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Tan
authors.forename: E A
authors.initials: EA
authors.lastname: Williams
authors.forename: A J
authors.initials: AJ
authors.lastname: Lancia
authors.forename: D S
authors.initials: DS
authors.lastname: Zahm
mesh_terms: D000818:Animals; D064026:Calbindins; D002452:Cell Count; D004298:Dopamine / Q000378:metabolism; D008297:Male; D008474:Medial Forebrain Bundle / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009714:Nucleus Accumbens / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D064030:S100 Calcium Binding Protein G / Q000378:metabolism*; D013378:Substantia Nigra / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*; D017557:Ventral Tegmental Area / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology
chemical_list: D064026:Calbindins; D064030:S100 Calcium Binding Protein G; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine