Enhanced Neuroplasticity by the Metabolic Enhancer Piracetam Associated with Improved Mitochondrial Dynamics and Altered Permeability Transition Pore Function
The mitochondrial cascade hypothesis of dementia assumes mitochondrial dysfunction leading to reduced energy supply, impaired neuroplasticity, and finally cell death as one major pathomechanism underlying the continuum from brain aging over mild cognitive impairment to initial and advanced late onse...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2016-01-01
|
| Series: | Neural Plasticity |
| Online Access: | http://dx.doi.org/10.1155/2016/8075903 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832556585665167360 |
|---|---|
| author | Carola Stockburger Davide Miano Thea Pallas Kristina Friedland Walter E. Müller |
| author_facet | Carola Stockburger Davide Miano Thea Pallas Kristina Friedland Walter E. Müller |
| author_sort | Carola Stockburger |
| collection | DOAJ |
| description | The mitochondrial cascade hypothesis of dementia assumes mitochondrial dysfunction leading to reduced energy supply, impaired neuroplasticity, and finally cell death as one major pathomechanism underlying the continuum from brain aging over mild cognitive impairment to initial and advanced late onset Alzheimer’s disease. Accordingly, improving mitochondrial function has become an important strategy to treat the early stages of this continuum. The metabolic enhancer piracetam has been proposed as possible prototype for those compounds by increasing impaired mitochondrial function and related aspects like mechanisms of neuroplasticity. We here report that piracetam at therapeutically relevant concentrations improves neuritogenesis in the human cell line SH-SY5Y over conditions mirroring the whole spectrum of age-associated cognitive decline. These effects go parallel with improvement of impaired mitochondrial dynamics shifting back fission and fusion balance to the energetically more favorable fusion site. Impaired fission and fusion balance can also be induced by a reduction of the mitochondrial permeability transition pore (mPTP) function as atractyloside which indicates the mPTP has similar effects on mitochondrial dynamics. These changes are also reduced by piracetam. These findings suggest the mPTP as an important target for the beneficial effects of piracetam on mitochondrial function. |
| format | Article |
| id | doaj-art-013feda074a54b42822f73e5a8f14459 |
| institution | Kabale University |
| issn | 2090-5904 1687-5443 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Neural Plasticity |
| spelling | doaj-art-013feda074a54b42822f73e5a8f144592025-02-03T05:44:52ZengWileyNeural Plasticity2090-59041687-54432016-01-01201610.1155/2016/80759038075903Enhanced Neuroplasticity by the Metabolic Enhancer Piracetam Associated with Improved Mitochondrial Dynamics and Altered Permeability Transition Pore FunctionCarola Stockburger0Davide Miano1Thea Pallas2Kristina Friedland3Walter E. Müller4Department of Pharmacology, University of Frankfurt and Biocenter, Goethe University, 60438 Frankfurt, GermanyDepartment of Pharmacology, University of Frankfurt and Biocenter, Goethe University, 60438 Frankfurt, GermanyDepartment of Pharmacology, University of Frankfurt and Biocenter, Goethe University, 60438 Frankfurt, GermanyMolecular and Clinical Pharmacy, Department of Chemistry and Pharmacy, Friedrich-Alexander-Universität Erlangen-Nuremberg, 91058 Erlangen, GermanyDepartment of Pharmacology, University of Frankfurt and Biocenter, Goethe University, 60438 Frankfurt, GermanyThe mitochondrial cascade hypothesis of dementia assumes mitochondrial dysfunction leading to reduced energy supply, impaired neuroplasticity, and finally cell death as one major pathomechanism underlying the continuum from brain aging over mild cognitive impairment to initial and advanced late onset Alzheimer’s disease. Accordingly, improving mitochondrial function has become an important strategy to treat the early stages of this continuum. The metabolic enhancer piracetam has been proposed as possible prototype for those compounds by increasing impaired mitochondrial function and related aspects like mechanisms of neuroplasticity. We here report that piracetam at therapeutically relevant concentrations improves neuritogenesis in the human cell line SH-SY5Y over conditions mirroring the whole spectrum of age-associated cognitive decline. These effects go parallel with improvement of impaired mitochondrial dynamics shifting back fission and fusion balance to the energetically more favorable fusion site. Impaired fission and fusion balance can also be induced by a reduction of the mitochondrial permeability transition pore (mPTP) function as atractyloside which indicates the mPTP has similar effects on mitochondrial dynamics. These changes are also reduced by piracetam. These findings suggest the mPTP as an important target for the beneficial effects of piracetam on mitochondrial function.http://dx.doi.org/10.1155/2016/8075903 |
| spellingShingle | Carola Stockburger Davide Miano Thea Pallas Kristina Friedland Walter E. Müller Enhanced Neuroplasticity by the Metabolic Enhancer Piracetam Associated with Improved Mitochondrial Dynamics and Altered Permeability Transition Pore Function Neural Plasticity |
| title | Enhanced Neuroplasticity by the Metabolic Enhancer Piracetam Associated with Improved Mitochondrial Dynamics and Altered Permeability Transition Pore Function |
| title_full | Enhanced Neuroplasticity by the Metabolic Enhancer Piracetam Associated with Improved Mitochondrial Dynamics and Altered Permeability Transition Pore Function |
| title_fullStr | Enhanced Neuroplasticity by the Metabolic Enhancer Piracetam Associated with Improved Mitochondrial Dynamics and Altered Permeability Transition Pore Function |
| title_full_unstemmed | Enhanced Neuroplasticity by the Metabolic Enhancer Piracetam Associated with Improved Mitochondrial Dynamics and Altered Permeability Transition Pore Function |
| title_short | Enhanced Neuroplasticity by the Metabolic Enhancer Piracetam Associated with Improved Mitochondrial Dynamics and Altered Permeability Transition Pore Function |
| title_sort | enhanced neuroplasticity by the metabolic enhancer piracetam associated with improved mitochondrial dynamics and altered permeability transition pore function |
| url | http://dx.doi.org/10.1155/2016/8075903 |
| work_keys_str_mv | AT carolastockburger enhancedneuroplasticitybythemetabolicenhancerpiracetamassociatedwithimprovedmitochondrialdynamicsandalteredpermeabilitytransitionporefunction AT davidemiano enhancedneuroplasticitybythemetabolicenhancerpiracetamassociatedwithimprovedmitochondrialdynamicsandalteredpermeabilitytransitionporefunction AT theapallas enhancedneuroplasticitybythemetabolicenhancerpiracetamassociatedwithimprovedmitochondrialdynamicsandalteredpermeabilitytransitionporefunction AT kristinafriedland enhancedneuroplasticitybythemetabolicenhancerpiracetamassociatedwithimprovedmitochondrialdynamicsandalteredpermeabilitytransitionporefunction AT walteremuller enhancedneuroplasticitybythemetabolicenhancerpiracetamassociatedwithimprovedmitochondrialdynamicsandalteredpermeabilitytransitionporefunction |