Molecular mechanisms of neuronal death in the dorsal lateral geniculate nucleus following visual cortical lesions.
We investigated the molecular mechanisms of cell death in the dorsal lateral geniculate nucleus of the rat, following suction lesion of the visual cortex at birth or in the third postnatal week, using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) technique and immunohistochemistry for caspase-3, -7, -8, and cleaved poly(ADP-ribose) polymerase. Following lesion at birth, TUNEL-positive neurons were found in the dorsal lateral geniculate nucleus between 24 h and 3 days after lesion, with a peak on the second day. Shorter survival times (12-18 h) resulted in labeling of very few neurons in dorsal lateral geniculate nucleus and of several neurons in the perilesional cortex. Activated caspase-3 was expressed from the first to the third days after lesion, whereas cleaved poly(ADP-ribose) polymerase and activated caspase-8 were expressed on the second and third day. Activated caspase-7 was expressed mainly in pretectal nuclei. Caspase-3 activation coincided with the appearance of TUNEL-positive profiles, but decreased earlier than TUNEL. In the ipsi- and contralateral cerebral cortex, all parameters were unchanged. In animals lesioned in the third week, rare apoptotic thalamic neurons were detected as TUNEL- and activated caspase-3-positive profiles 2 days after cortical ablation, and were still present 1 week after lesion.Thus, early target ablation has dramatic effects on neonatal thalamic neurons, which die following activation of caspases 3 and 8. In contrast, cortical neurons are relatively unaffected by target deprivation. Compared with early lesions, late lesions induce a limited thalamic cell death, that persists over time.
Repici
M
M
Department of Anatomy, Pharmacology and Forensic Medicine, University of Torino Medical School, Corso M. d'Azeglio 52, 10126, Torino, Italy. mariaelena.repici@unito.it
Atzori
C
C
Migheli
A
A
Vercelli
A
A
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3; D053179:Caspase 7; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D002450:Cell Communication / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology*; D003714:Denervation; D007839:Functional Laterality / Q000502:physiology; D005829:Geniculate Bodies / Q000254:growth & development* / Q000378:metabolism / Q000503:physiopathology; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D019636:Neurodegenerative Diseases / Q000473:pathology / Q000503:physiopathology*; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000502:physiology; D014793:Visual Cortex / Q000254:growth & development* / Q000378:metabolism / Q000503:physiopathology; D014795:Visual Pathways / Q000254:growth & development* / Q000378:metabolism / Q000503:physiopathology
D011065:Poly(ADP-ribose) Polymerases; C505410:Casp3 protein, rat; C505528:Casp8 protein, rat; C506435:Casp9 protein, rat; D053148:Caspase 3; D053179:Caspase 7; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases