Limits...
Ginkgolides protect against amyloid-beta1-42-mediated synapse damage in vitro.

Bate C, Tayebi M, Williams A - Mol Neurodegener (2008)

Bottom Line: The early stages of Alzheimer's disease (AD) are closely associated with the production of the Abeta1-42 peptide, loss of synapses and gradual cognitive decline.This protective effect was achieved with nanomolar concentrations of ginkgolides.This effect of PAF was greatly reduced by pre-treatment with ginkgolide B.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pathology and Infectious Diseases, Royal Veterinary College, Hawkshead Lane, North Mymms, Herts, AL9 7TA, UK. cbate@rvc.ac.uk.

ABSTRACT

Background: The early stages of Alzheimer's disease (AD) are closely associated with the production of the Abeta1-42 peptide, loss of synapses and gradual cognitive decline. Since some epidemiological studies showed that EGb 761, an extract from the leaves of the Ginkgo biloba tree, had a beneficial effect on mild forms of AD, the effects of some of the major components of the EGb 761 extract (ginkgolides A and B, myricetin and quercetin) on synapse damage in response to Abeta1-42 were examined.

Results: The addition of Abeta1-42 to cortical or hippocampal neurons reduced the amounts of cell associated synaptophysin, a pre-synaptic membrane protein that is essential for neurotransmission, indicating synapse damage. The effects of Abeta1-42 on synapses were apparent at concentrations approximately 100 fold less than that required to kill neurons; the synaptophysin content of neuronal cultures was reduced by 50% by 50 nM Abeta1-42. Pre-treatment of cortical or hippocampal neuronal cultures with ginkgolides A or B, but not with myrecitin or quercetin, protected against Abeta1-42-induced loss of synaptophysin. This protective effect was achieved with nanomolar concentrations of ginkgolides. Previous studies indicated that the ginkgolides are platelet-activating factor (PAF) receptor antagonists and here we show that Abeta1-42-induced loss of synaptophysin from neuronal cultures was also reduced by pre-treatment with other PAF antagonists (Hexa-PAF and CV6209). PAF, but not lyso-PAF, mimicked the effects Abeta1-42 and caused a dose-dependent reduction in the synaptophysin content of neurons. This effect of PAF was greatly reduced by pre-treatment with ginkgolide B. In contrast, ginkgolide B did not affect the loss of synaptophysin in neurons incubated with prostaglandin E2.

Conclusion: Pre-treatment with ginkgolides A or B protects neurons against Abeta1-42-induced synapse damage. These ginkgolides also reduced the effects of PAF, but not those of prostaglandin E2, on the synaptophysin content of neuronal cultures, results consistent with prior reports that ginkgolides act as PAF receptor antagonists. Such observations suggest that the ginkgolides are active components of Ginkgo biloba preparations and may protect against the synapse damage and the cognitive loss seen during the early stages of AD.

No MeSH data available.


Related in: MedlinePlus

Ginkgolide B protects cortical neurons against Aβ1–42-induced loss of synaptophysin. Primary cortical neurons were pre-treated for 3 hours with control medium (solid circle) or with 1 μM ginkgolide B (hollow circle) and subsequently incubated for 24 hours with different concentrations of Aβ1–42 as shown. Each point represents the mean synaptophysin content ± SD from 9 observations.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2254622&req=5

Figure 3: Ginkgolide B protects cortical neurons against Aβ1–42-induced loss of synaptophysin. Primary cortical neurons were pre-treated for 3 hours with control medium (solid circle) or with 1 μM ginkgolide B (hollow circle) and subsequently incubated for 24 hours with different concentrations of Aβ1–42 as shown. Each point represents the mean synaptophysin content ± SD from 9 observations.

Mentions: The synaptoprotective effect of ginkgolide B was competitive; while the concentration of Aβ1–42 required to reduce the synaptophysin content of untreated neurons by 50% was 50 nM, 8 μM Aβ1–42 was required to have the same effect in neurons treated with 1 μM ginkgolide B (Figure 3). This effect of ginkgolide B required pre-treatment; there was no significant difference between the amount of synaptophysin in neuronal cultures incubated with 200 nM Aβ1–42 and neuronal cultures in which 1 μM ginkgolide B was added to neurons 30 minutes after the addition of 200 nM Aβ1–42 (27 units ± 5 v 30 ± 4, n = 6, P > 0.05).


Ginkgolides protect against amyloid-beta1-42-mediated synapse damage in vitro.

Bate C, Tayebi M, Williams A - Mol Neurodegener (2008)

Ginkgolide B protects cortical neurons against Aβ1–42-induced loss of synaptophysin. Primary cortical neurons were pre-treated for 3 hours with control medium (solid circle) or with 1 μM ginkgolide B (hollow circle) and subsequently incubated for 24 hours with different concentrations of Aβ1–42 as shown. Each point represents the mean synaptophysin content ± SD from 9 observations.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2254622&req=5

Figure 3: Ginkgolide B protects cortical neurons against Aβ1–42-induced loss of synaptophysin. Primary cortical neurons were pre-treated for 3 hours with control medium (solid circle) or with 1 μM ginkgolide B (hollow circle) and subsequently incubated for 24 hours with different concentrations of Aβ1–42 as shown. Each point represents the mean synaptophysin content ± SD from 9 observations.
Mentions: The synaptoprotective effect of ginkgolide B was competitive; while the concentration of Aβ1–42 required to reduce the synaptophysin content of untreated neurons by 50% was 50 nM, 8 μM Aβ1–42 was required to have the same effect in neurons treated with 1 μM ginkgolide B (Figure 3). This effect of ginkgolide B required pre-treatment; there was no significant difference between the amount of synaptophysin in neuronal cultures incubated with 200 nM Aβ1–42 and neuronal cultures in which 1 μM ginkgolide B was added to neurons 30 minutes after the addition of 200 nM Aβ1–42 (27 units ± 5 v 30 ± 4, n = 6, P > 0.05).

Bottom Line: The early stages of Alzheimer's disease (AD) are closely associated with the production of the Abeta1-42 peptide, loss of synapses and gradual cognitive decline.This protective effect was achieved with nanomolar concentrations of ginkgolides.This effect of PAF was greatly reduced by pre-treatment with ginkgolide B.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pathology and Infectious Diseases, Royal Veterinary College, Hawkshead Lane, North Mymms, Herts, AL9 7TA, UK. cbate@rvc.ac.uk.

ABSTRACT

Background: The early stages of Alzheimer's disease (AD) are closely associated with the production of the Abeta1-42 peptide, loss of synapses and gradual cognitive decline. Since some epidemiological studies showed that EGb 761, an extract from the leaves of the Ginkgo biloba tree, had a beneficial effect on mild forms of AD, the effects of some of the major components of the EGb 761 extract (ginkgolides A and B, myricetin and quercetin) on synapse damage in response to Abeta1-42 were examined.

Results: The addition of Abeta1-42 to cortical or hippocampal neurons reduced the amounts of cell associated synaptophysin, a pre-synaptic membrane protein that is essential for neurotransmission, indicating synapse damage. The effects of Abeta1-42 on synapses were apparent at concentrations approximately 100 fold less than that required to kill neurons; the synaptophysin content of neuronal cultures was reduced by 50% by 50 nM Abeta1-42. Pre-treatment of cortical or hippocampal neuronal cultures with ginkgolides A or B, but not with myrecitin or quercetin, protected against Abeta1-42-induced loss of synaptophysin. This protective effect was achieved with nanomolar concentrations of ginkgolides. Previous studies indicated that the ginkgolides are platelet-activating factor (PAF) receptor antagonists and here we show that Abeta1-42-induced loss of synaptophysin from neuronal cultures was also reduced by pre-treatment with other PAF antagonists (Hexa-PAF and CV6209). PAF, but not lyso-PAF, mimicked the effects Abeta1-42 and caused a dose-dependent reduction in the synaptophysin content of neurons. This effect of PAF was greatly reduced by pre-treatment with ginkgolide B. In contrast, ginkgolide B did not affect the loss of synaptophysin in neurons incubated with prostaglandin E2.

Conclusion: Pre-treatment with ginkgolides A or B protects neurons against Abeta1-42-induced synapse damage. These ginkgolides also reduced the effects of PAF, but not those of prostaglandin E2, on the synaptophysin content of neuronal cultures, results consistent with prior reports that ginkgolides act as PAF receptor antagonists. Such observations suggest that the ginkgolides are active components of Ginkgo biloba preparations and may protect against the synapse damage and the cognitive loss seen during the early stages of AD.

No MeSH data available.


Related in: MedlinePlus