Natural and lesion-induced apoptosis in the rat striatum during development.
We evaluated the pattern of apoptosis in the rat striatum during normal development and in two models of lesion-induced cell death. Lesions included i) unilateral ablations of the cerebral cortex at different postnatal ages, and ii) early postnatal lesions of the catecholaminergic afferent systems of the striatum with 6-hydroxydopamine (6-OHDA). Dying cells were identified as apoptotic using the TUNEL (terminal deoxynucleotidyl-transferase-mediated dUTP-biotin nick end labeling) method at the light and electron microscopic levels. Moreover, we used immunohistochemistry for the apoptotic markers active caspase-3 and fractin. TUNEL+ cells were present in the striatum during the first four postnatal weeks. Their frequency was high during the first postnatal week and peaked at postnatal day (P)5. Cortical lesions at birth, in contrast to those performed at later stages, induced a significant increase in the frequency of TUNEL+ cells in the ipsilateral striatum, which peaked at seven days postlesion. 6-OHDA lesions resulted in a similar and significant increase in the frequency of TUNEL+ cells in the striatum, which also peaked at P7. We also showed that cortical lesions at P0 and 6-OHDA lesions resulted in a reduction in the frequency, as well as in alterations of the morphology of gamma-aminobutyric acid (GABA)-immunoreactive (ir) neurons in the striatum. We suggest that: i) apoptosis in the striatum is temporally coordinated with maturation events in this area and ii) early developmental lesions of major afferent pathways to the striatum affect both the survival and phenotype of striatal neurons.
Mellios
K
K
Department of Anatomy Histology and Embryology, Faculty of Veterinary Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.
Zacharaki
T
T
Sophou
S
S
Latsari
M
M
Antonopoulos
J
J
Dinopoulos
A
A
Parnavelas
J G
JG
Dori
I
I
D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000601:surgery; D053148:Caspase 3 / Q000378:metabolism; D003342:Corpus Striatum / Q000166:cytology / Q000254:growth & development* / Q000502:physiology*; D003603:Cytotoxins / Q000494:pharmacology; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008854:Microscopy, Electron; D009474:Neurons / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D016627:Oxidopamine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D003603:Cytotoxins; D005680:gamma-Aminobutyric Acid; D016627:Oxidopamine; D053148:Caspase 3