Abstract
We studied the neurotoxic effects of β25-35 amyloid fragment (β25-35) on cerebellar granule cells and the intracellular mechanisms involved. Treatment for 3 days with peptide greatly reduced the survival of 1 day in vitro (DIV) cultures kept in 5 mM KCl but slightly modified the survival of 25 mM KCl- cultured cerebellar granule cells. We also studied the effect of glutamate on survival of undifferentiated cerebellar granules. We report no neurotoxic effect of glutamate on 3-DIV-treated cultures; whereas in β25-35-pretreated cells, a significant glutamate toxicity was observed. Treatment of 6-DIV cells with β25-35, performed with 25 mM KCl, induced a late but significant neurotoxic effect after 5 days of exposure, and death occurred within 8 days. Differentiated cerebellar granule cells were also sensitive to glutamate- related neurotoxicity, and this effect was enhanced by β25-35 pretreatment. To study the molecular mechanisms underlying the neurotoxic effects of β25- 35, changes in calcium homeostasis after glutamate stimulation were evaluated in control and β25-35-treated cells. β25-35 did not affect basal [Ca2+](i) but modified glutamate-induced [Ca2+](i) increase, causing a sustained plateau phase that persisted even after the removal of the agonist. These results show that β25-35 induces neurotoxicity in cerebellar granule cells and that this effect is related to modifications in the control of calcium homeostasis.
| Original language | English |
|---|---|
| Pages (from-to) | 1995-2003 |
| Number of pages | 9 |
| Journal | Journal of Neurochemistry |
| Volume | 66 |
| Issue number | 5 |
| Publication status | Published - May 1996 |
Fingerprint
Keywords
- β-Amyloid
- Calcium
- Glutamate
- Neurodegeneration
- NMDA antagonists
ASJC Scopus subject areas
- Biochemistry
- Cellular and Molecular Neuroscience
Cite this
β25-35 alters calcium homeostasis and induces neurotoxicity in cerebellar granule cells. / Scorziello, Antonella; Meucci, Olimpia; Florio, Tullio; Fattore, Morena; Forloni, Gianluigi; Salmona, Mario; Schettini, Gennaro.
In: Journal of Neurochemistry, Vol. 66, No. 5, 05.1996, p. 1995-2003.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - β25-35 alters calcium homeostasis and induces neurotoxicity in cerebellar granule cells
AU - Scorziello, Antonella
AU - Meucci, Olimpia
AU - Florio, Tullio
AU - Fattore, Morena
AU - Forloni, Gianluigi
AU - Salmona, Mario
AU - Schettini, Gennaro
PY - 1996/5
Y1 - 1996/5
N2 - We studied the neurotoxic effects of β25-35 amyloid fragment (β25-35) on cerebellar granule cells and the intracellular mechanisms involved. Treatment for 3 days with peptide greatly reduced the survival of 1 day in vitro (DIV) cultures kept in 5 mM KCl but slightly modified the survival of 25 mM KCl- cultured cerebellar granule cells. We also studied the effect of glutamate on survival of undifferentiated cerebellar granules. We report no neurotoxic effect of glutamate on 3-DIV-treated cultures; whereas in β25-35-pretreated cells, a significant glutamate toxicity was observed. Treatment of 6-DIV cells with β25-35, performed with 25 mM KCl, induced a late but significant neurotoxic effect after 5 days of exposure, and death occurred within 8 days. Differentiated cerebellar granule cells were also sensitive to glutamate- related neurotoxicity, and this effect was enhanced by β25-35 pretreatment. To study the molecular mechanisms underlying the neurotoxic effects of β25- 35, changes in calcium homeostasis after glutamate stimulation were evaluated in control and β25-35-treated cells. β25-35 did not affect basal [Ca2+](i) but modified glutamate-induced [Ca2+](i) increase, causing a sustained plateau phase that persisted even after the removal of the agonist. These results show that β25-35 induces neurotoxicity in cerebellar granule cells and that this effect is related to modifications in the control of calcium homeostasis.
AB - We studied the neurotoxic effects of β25-35 amyloid fragment (β25-35) on cerebellar granule cells and the intracellular mechanisms involved. Treatment for 3 days with peptide greatly reduced the survival of 1 day in vitro (DIV) cultures kept in 5 mM KCl but slightly modified the survival of 25 mM KCl- cultured cerebellar granule cells. We also studied the effect of glutamate on survival of undifferentiated cerebellar granules. We report no neurotoxic effect of glutamate on 3-DIV-treated cultures; whereas in β25-35-pretreated cells, a significant glutamate toxicity was observed. Treatment of 6-DIV cells with β25-35, performed with 25 mM KCl, induced a late but significant neurotoxic effect after 5 days of exposure, and death occurred within 8 days. Differentiated cerebellar granule cells were also sensitive to glutamate- related neurotoxicity, and this effect was enhanced by β25-35 pretreatment. To study the molecular mechanisms underlying the neurotoxic effects of β25- 35, changes in calcium homeostasis after glutamate stimulation were evaluated in control and β25-35-treated cells. β25-35 did not affect basal [Ca2+](i) but modified glutamate-induced [Ca2+](i) increase, causing a sustained plateau phase that persisted even after the removal of the agonist. These results show that β25-35 induces neurotoxicity in cerebellar granule cells and that this effect is related to modifications in the control of calcium homeostasis.
KW - β-Amyloid
KW - Calcium
KW - Glutamate
KW - Neurodegeneration
KW - NMDA antagonists
UR - http://www.scopus.com/inward/record.url?scp=0029888017&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029888017&partnerID=8YFLogxK
M3 - Article
C2 - 8780028
AN - SCOPUS:0029888017
VL - 66
SP - 1995
EP - 2003
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
SN - 0022-3042
IS - 5
ER -