Apoptosis in the rat basal forebrain during development and following lesions of connections.
Evidence suggests that neurotrophins are essential for the survival and phenotypic maintenance of cholinergic basal forebrain (BF) neurons. We evaluated the pattern of programmed cell death in the BF of the rat during development and after ablations of the cerebral cortex, a major target area and source of neurotrophins for BF neurons. We identified dying cells using the TUNEL (terminal deoxynucleotidyl-transferase-mediated dUTP-biotin nick end labelling) method and confirmed their apoptotic morphology with electron microscopy. Moreover, we demonstrated the expression of the apoptotic marker active caspase-3 in cells with features of apoptosis. TUNEL(+) cells were present in the developing BF during the first two postnatal weeks. Their frequency peaked at postnatal day (P)1 and at P5. TUNEL used in conjunction with immunofluorescence for neuronal nuclear protein (NeuN) showed that, at both peak stages, the majority of apoptotic cells were neurons. Extensive lesions of the cerebral cortex at different ages (P0, P7 and P14) did not induce significant changes in the frequency of apoptotic BF neurons. However, they resulted in alterations in the morphological phenotype of choline acetyltransferase (ChAT)-immunoreactive neurons in the BF, and a reduction in their number which was inversely proportional to the age at which the lesions were performed. We suggest that: (i) apoptosis is temporally coordinated with the morphological and neurochemical differentiation of BF neurons and the establishment of connections with their target areas; and (ii) cortical ablations do not affect the survival of BF neurons, but they influence the phenotype of cholinergic BF neurons.
Sophou
Stavroula
S
Department of Anatomy and Histology, Faculty of Veterinary Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.
Dori
Ioanna
I
Antonopoulos
John
J
Parnavelas
John G
JG
Dinopoulos
Athanasios
A
D000109:Acetylcholine / Q000096:biosynthesis; D000375:Aging / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000502:physiology*; D020532:Basal Nucleus of Meynert / Q000196:embryology* / Q000254:growth & development* / Q000378:metabolism; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002540:Cerebral Cortex / Q000293:injuries / Q000378:metabolism / Q000503:physiopathology; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004268:DNA-Binding Proteins; D003714:Denervation; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D046529:Microscopy, Electron, Transmission; D009410:Nerve Degeneration / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009434:Neural Pathways / Q000293:injuries / Q000378:metabolism / Q000503:physiopathology*; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D009687:Nuclear Proteins / Q000378:metabolism; D010641:Phenotype; D051381:Rats; D017208:Rats, Wistar
D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; C492380:NeuN protein, mouse; D009687:Nuclear Proteins; D002795:Choline O-Acetyltransferase; C505409:Casp3 protein, mouse; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D000109:Acetylcholine