Chapter 37: PrPSc causes nerve cell death and stimulates astrocyte proliferation: a paradox

DeArmond, Stephen J.; Kristensson, Krister; Bowler, R.P.

doi:10.1016/s0079-6123(08)61771-9

Cited by 27 publications

(13 citation statements)

References 46 publications

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“…Recently, PrP peptide fragments deduced from human cDNA sequences were shown to demonstrate cleavage of nuclear DNA in internucleosomal regions in chronically exposed primary rat hip- pocampal cultures [9]. These results support the causitive relationship between PrP sc infection and neuronal cell death [5,22], and also add credibility to the hypothesis that scrapie infection-induced neuronal cell death is by apoptosis. The major histocompatibility complex (MHC) class I and class II genes have both been shown to have increased levels of expression after scrapie infection [7].…”

Section: Resultsmentioning

confidence: 56%

Detection of apoptosis induced DNA cleavage in scrapie-infected sheep brain

Fairbairn

1994

FEMS Microbiology Letters

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Abstract:The pathogenesis and molecular basis of nerve cell death which accompanies scrapie infections in sheep are not well understood. Degeneration of neurons in culture caused by prion protein fragments has recently been reported to be consistent with mechanisms of cell death by apoptosis or programmed cell death. Apoptosis activation during prion°related encephalopathies has not yet been established in vivo. We report here the detection of DNA damage consistent with apoptosis in the brain cells of sheep infected with scrapie using laser scanning microscopic analysis of the single cell gel assay. We suggest that this DNA fragmentation is the result of the activation of the mechanisms characteristic of apoptotic cell death.

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Section: Resultsmentioning

confidence: 56%

Detection of apoptosis induced DNA cleavage in scrapie-infected sheep brain

Fairbairn

1994

FEMS Microbiology Letters

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“…The attenuated intracellular Ca2+ response in ScN2a cells correlated temporally with the weak IP, response since increased [Ca2+Ii reached a peak about 20 to 30 seconds after Bk exposure and was near background levels at 40 seconds. The attenuated intracellular Ca2+ response in ScN2a cells correlated temporally with the weak IP, response since increased [Ca2+Ii reached a peak about 20 to 30 seconds after Bk exposure and was near background levels at 40 seconds.…”

Section: The Mean and Standard Deviation Of C6-nbd-cg-pc Mobility (mentioning

confidence: 79%

“…In one experiment, IP, concentration in ScN,a cells was measured 30 and 40 seconds after exposure to Bk and was found to be 0.8 pM at 30 seconds and 0.39 pM at 40 seconds, in contrast to the level in N,a cells at 40 seconds, which was 10.5 pM. In one experiment, IP, concentration in ScN,a cells was measured 30 and 40 seconds after exposure to Bk and was found to be 0.8 pM at 30 seconds and 0.39 pM at 40 seconds, in contrast to the level in N,a cells at 40 seconds, which was 10.5 pM.…”

Section: Measurement Of Ip3mentioning

confidence: 96%

Decreased receptor-mediated calcium response in prion-infected cells correlates with decreased membrane fluidity and IP sub 3 release

Wong¹,

Qiu²,

Hyun³

et al. 1996

Neurology

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The most characteristic neuropathologic features of prion diseases are accumulation of PrPSc in the brain and vacuolation of neurons. Neuronal vacuolation suggests plasma membrane dysfunction. In an earlier study, we found that bradykinin (Bk)-stimulated Ca2+ responses in scrapie-infected ScN2a cells were reduced by 30 to 50% compared with uninfected N2a cells. In this study, we investigated the cause. The IP3 second-messenger response to Bk stimulation was reduced 90%, indicating that a defect occurs in the plasma membrane. Receptor-binding assays showed a 3- to 4-fold increase in Bk receptor numbers on ScN2a cells; however, their binding affinity was reduced 5- to 13-fold, which may account for the decreased IP3 and Ca2+ responses. These results argue that scrapie causes a more fundamental change in the properties of the plasma membrane. We verified this by fluorescence recovery after photobleaching (FRAP) analysis with a lipid probe that measures lateral membrane fluidity. A 7-fold reduction of fluidity was found. These results support the hypothesis that the conversion of PrPc to PrPSc or the accumulation of PrPSc in scrapie-infected cells alters the composition of their plasma membranes that secondarily causes the abnormal receptor-mediated function.

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“…GPI-anchor the form of PrP27-3", Figure 1) has been shown in vitro to stimulate proliferation (but not hypertrophy) of astrocytes [30]. Several lines of evidence suggest P r F plays a role in the interplay of neurones and glial cells (reviewed in [30]), and the nerve damage caused by a reactive astrocytic gliosis stimulated by PrPS' may be aggravated by the…”

Section: 'mentioning

confidence: 99%

“…Several lines of evidence suggest P r F plays a role in the interplay of neurones and glial cells (reviewed in [30]), and the nerve damage caused by a reactive astrocytic gliosis stimulated by PrPS' may be aggravated by the…”

Section: 'mentioning

confidence: 99%