Galanin attenuates β-amyloid (Aβ) toxicity in rat cholinergic basal forebrain neurons
In brains of Alzheimer's disease (AD) patients, expression of the neuropeptide galanin is significantly upregulated and galanin-immunoreactive fibers hypertrophy and hyperinnervate cholinergic neurons of the basal forebrain. However, the role of galanin in AD, whether it is detrimental or neuro...
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| Format: | Article |
| Language: | English |
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Elsevier
2006-02-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996105002275 |
| _version_ | 1818724669797171200 |
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| author | Xiling Ding David MacTavish Satyabrata Kar Jack H. Jhamandas |
| author_facet | Xiling Ding David MacTavish Satyabrata Kar Jack H. Jhamandas |
| author_sort | Xiling Ding |
| collection | DOAJ |
| description | In brains of Alzheimer's disease (AD) patients, expression of the neuropeptide galanin is significantly upregulated and galanin-immunoreactive fibers hypertrophy and hyperinnervate cholinergic neurons of the basal forebrain. However, the role of galanin in AD, whether it is detrimental or neuroprotective, remains controversial. In this study, using primary cultured neurons from the rat basal forebrain, we show that pretreatment with galanin protects cholinergic neurons against β-amyloid-induced apoptotic cell death as judged by visual observation, MTT assay, Live/dead cell assay, TUNEL and cleaved caspase-3 staining. These effects are mimicked by the galanin receptor 2 (GALR2) agonist, AR-M1896. Western blot analysis revealed Aβ-induced decrease in phospho-PKC and phospho-Akt levels was reversed by galanin. Galanin also attenuated cleavage of caspases-3 and -9 following exposure to Aβ. These findings support a neuroprotective role for galanin and may have implications for development of compounds based on this peptide to treat AD. |
| first_indexed | 2024-12-17T21:30:06Z |
| format | Article |
| id | doaj.art-47a673c8f781415da9bb5556c8cd704a |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-17T21:30:06Z |
| publishDate | 2006-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-47a673c8f781415da9bb5556c8cd704a2022-12-21T21:31:55ZengElsevierNeurobiology of Disease1095-953X2006-02-01212413420Galanin attenuates β-amyloid (Aβ) toxicity in rat cholinergic basal forebrain neuronsXiling Ding0David MacTavish1Satyabrata Kar2Jack H. Jhamandas3Division of Neurology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada T6G 2S2; Centre for Alzheimer and Neurodegenerative Research, University of Alberta, Edmonton, Alberta, Canada T6G 2S2Division of Neurology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada T6G 2S2; Centre for Alzheimer and Neurodegenerative Research, University of Alberta, Edmonton, Alberta, Canada T6G 2S2Division of Neurology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada T6G 2S2; Department of Psychiatry, University of Alberta, Edmonton, Alberta, Canada T6G 2S2; Centre for Alzheimer and Neurodegenerative Research, University of Alberta, Edmonton, Alberta, Canada T6G 2S2Division of Neurology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada T6G 2S2; Centre for Alzheimer and Neurodegenerative Research, University of Alberta, Edmonton, Alberta, Canada T6G 2S2; Corresponding author. Division of Neurology, 530 Heritage Medical Research Centre, University of Alberta, Edmonton, Alberta, Canada T6G 2S2. Fax: +1 780 407 3410.In brains of Alzheimer's disease (AD) patients, expression of the neuropeptide galanin is significantly upregulated and galanin-immunoreactive fibers hypertrophy and hyperinnervate cholinergic neurons of the basal forebrain. However, the role of galanin in AD, whether it is detrimental or neuroprotective, remains controversial. In this study, using primary cultured neurons from the rat basal forebrain, we show that pretreatment with galanin protects cholinergic neurons against β-amyloid-induced apoptotic cell death as judged by visual observation, MTT assay, Live/dead cell assay, TUNEL and cleaved caspase-3 staining. These effects are mimicked by the galanin receptor 2 (GALR2) agonist, AR-M1896. Western blot analysis revealed Aβ-induced decrease in phospho-PKC and phospho-Akt levels was reversed by galanin. Galanin also attenuated cleavage of caspases-3 and -9 following exposure to Aβ. These findings support a neuroprotective role for galanin and may have implications for development of compounds based on this peptide to treat AD.http://www.sciencedirect.com/science/article/pii/S0969996105002275Alzheimer's diseaseAR-M1896Diagonal band of BrocaNeuroprotectionNeurodegenerationApoptosis |
| spellingShingle | Xiling Ding David MacTavish Satyabrata Kar Jack H. Jhamandas Galanin attenuates β-amyloid (Aβ) toxicity in rat cholinergic basal forebrain neurons Neurobiology of Disease Alzheimer's disease AR-M1896 Diagonal band of Broca Neuroprotection Neurodegeneration Apoptosis |
| title | Galanin attenuates β-amyloid (Aβ) toxicity in rat cholinergic basal forebrain neurons |
| title_full | Galanin attenuates β-amyloid (Aβ) toxicity in rat cholinergic basal forebrain neurons |
| title_fullStr | Galanin attenuates β-amyloid (Aβ) toxicity in rat cholinergic basal forebrain neurons |
| title_full_unstemmed | Galanin attenuates β-amyloid (Aβ) toxicity in rat cholinergic basal forebrain neurons |
| title_short | Galanin attenuates β-amyloid (Aβ) toxicity in rat cholinergic basal forebrain neurons |
| title_sort | galanin attenuates β amyloid aβ toxicity in rat cholinergic basal forebrain neurons |
| topic | Alzheimer's disease AR-M1896 Diagonal band of Broca Neuroprotection Neurodegeneration Apoptosis |
| url | http://www.sciencedirect.com/science/article/pii/S0969996105002275 |
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