Apoptosis in experimental cerebral malaria: spatial profile of cleaved caspase-3 and ultrastructural alterations in different disease stages

Lackner, P; Burger, C; Pfaller, K; Heussler, Volker; Helbok, R; Morandell, M; Broessner, G; Tannich, E; Schmutzhard, E; Beer, R (2007). Apoptosis in experimental cerebral malaria: spatial profile of cleaved caspase-3 and ultrastructural alterations in different disease stages. Neuropathology and Applied Neurobiology, 33(5), pp. 560-571. Wiley 10.1111/j.1365-2990.2007.00833.x

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Cerebral malaria (CM) is associated with high mortality and morbidity as a certain percentage of survivors suffers from persistent neurological sequelae. The mechanisms leading to death and functional impairments are yet not fully understood. This study investigated biochemical and morphological markers of apoptosis in the brains of mice infected with Plasmodium berghei ANKA. Cleaved caspase-3 was detected in the brains of animals with clinical signs of CM and immunoreactivity directly correlated with the clinical severity of the disease. Caudal parts of the brain showed more intense immunoreactivity for cleaved caspase-3. Double-labelling experiments revealed processing of caspase-3 primarily in neurons and oligodendrocytes. These cells also exhibited apoptotic-like morphological profiles in ultrastructural analysis. Further, cleavage of caspase-3 was found in endothelial cells. In contrast to neurons and oligodendrocytes, apoptosis of endothelial cells already occurred in early stages of the disease. Our results are the first to demonstrate processing of caspase-3 in different central nervous system cells of animals with CM. Apoptosis of endothelial cells may represent a critical issue for the development of the disease in the mouse model. Neurological signs and symptoms might be attributable, at least in part, to apoptotic degeneration of neurons and glia in advanced stages of murine CM.

Item Type:

Journal Article (Original Article)

Division/Institute:

08 Faculty of Science > Department of Biology > Institute of Cell Biology > Malaria
08 Faculty of Science > Department of Biology > Institute of Cell Biology

UniBE Contributor:

Heussler, Volker

Subjects:

500 Science > 570 Life sciences; biology

ISSN:

1365-2990

Publisher:

Wiley

Language:

English

Submitter:

Volker Heussler

Date Deposited:

06 Jul 2016 11:44

Last Modified:

07 Jul 2016 04:35

Publisher DOI:

10.1111/j.1365-2990.2007.00833.x

PubMed ID:

17442059

BORIS DOI:

10.7892/boris.84080

URI:

https://boris.unibe.ch/id/eprint/84080

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