ORCID
0000-0002-7229-7136
Department
Biological Sciences
Year of Study
3
Full-time or Part-time Study
Full-time
Level
Postgraduate
Presentation Type
Poster
Supervisor
Caitriona Guinane
Supervisor
Gerard O'Keeffe
Supervisor
Louise Collins
Abstract
Title: Short chain fatty acid combination treatment protects against 6-OHDA induced decrease in neurite growth in an in vitro model of Parkinson’s disease.
Authors: Alex Morris1, Louise M. Collins1,2,3, Gerard W. O’Keeffe2, Caitriona M. Guinane1
1 Department of Biological Sciences, Munster Technological University (MTU), Cork, Ireland.
2 Department of Anatomy & Neuroscience, University College Cork, Cork, Ireland.
3 Department of Physiology, University College Cork, Cork, Ireland.
Background: Parkinson’s disease (PD) is a neurodegenerative disorder characterized by dopaminergic neuron degeneration. This leads to motor dysfunction which is accompanied by gastrointestinal comorbidities such as constipation and gastroparesis. This results in a decline of gut microbial diversity and microbially-derived short chain fatty acids (SCFA). Recent in vivo studies have shown SCFAs to be anti-inflammatory and neuroprotective in various disease states. This suggests that SCFAs may protect against dopaminergic degeneration.
Methods: To test this hypothesis, this study utilized human neuroblastoma SH-SY5Y cells as a model of human dopaminergic neurons, to examine the effects of SCFAs on neurite growth as a single cell readout of neuroprotective efficacy, in the presence and absence of the well-established dopaminergic neurotoxin, 6-hydroxydopamine (6-OHDA) as an in vitro model of PD. 6-OHDA is selectively neurotoxic for dopamine neurons and induces mitochondrial dysfunction and oxidative stress thereby mimicking the characteristic cellular pathology seen in PD.
Results: Treatment with 25-200μM sodium acetate (NaOAc) for 72h, promoted neurite outgrowth in a concentration dependent manner. However, treatment with 50μM NaOAc did not protect against neurite retraction induced by treatment with 10μM 6-OHDA for 72h. In contrast, a combination of SCFAs of 50μM NaOAc, 50μM Sodium Butyrate (NaBu) and 50µM Sodium Propionate (NaPro) did protect against 6-OHDA-induced decreases in neurite growth at 72h.
Conclusions: Our findings provide proof-of-principle that combinations of SCFAs may protect against degeneration induced by a neurotoxin in a human dopaminergic cell line in vitro. This rationalizes the further study of SCFAs as potential neuroprotective therapies for PD.
Keywords:
Short chain fatty acids, Parkinson's Disease, 6-OHDA
Start Date
June 2022
End Date
June 2022
Recommended Citation
Morris, Alex, "Short chain fatty acid combination treatment protects against 6-OHDA induced decrease in neurite growth in an in vitro model of Parkinson’s disease." (2022). ORBioM (Open Research BioSciences Meeting). 4.
https://sword.cit.ie/orbiom/2022/posters/4
Included in
Short chain fatty acid combination treatment protects against 6-OHDA induced decrease in neurite growth in an in vitro model of Parkinson’s disease.
Title: Short chain fatty acid combination treatment protects against 6-OHDA induced decrease in neurite growth in an in vitro model of Parkinson’s disease.
Authors: Alex Morris1, Louise M. Collins1,2,3, Gerard W. O’Keeffe2, Caitriona M. Guinane1
1 Department of Biological Sciences, Munster Technological University (MTU), Cork, Ireland.
2 Department of Anatomy & Neuroscience, University College Cork, Cork, Ireland.
3 Department of Physiology, University College Cork, Cork, Ireland.
Background: Parkinson’s disease (PD) is a neurodegenerative disorder characterized by dopaminergic neuron degeneration. This leads to motor dysfunction which is accompanied by gastrointestinal comorbidities such as constipation and gastroparesis. This results in a decline of gut microbial diversity and microbially-derived short chain fatty acids (SCFA). Recent in vivo studies have shown SCFAs to be anti-inflammatory and neuroprotective in various disease states. This suggests that SCFAs may protect against dopaminergic degeneration.
Methods: To test this hypothesis, this study utilized human neuroblastoma SH-SY5Y cells as a model of human dopaminergic neurons, to examine the effects of SCFAs on neurite growth as a single cell readout of neuroprotective efficacy, in the presence and absence of the well-established dopaminergic neurotoxin, 6-hydroxydopamine (6-OHDA) as an in vitro model of PD. 6-OHDA is selectively neurotoxic for dopamine neurons and induces mitochondrial dysfunction and oxidative stress thereby mimicking the characteristic cellular pathology seen in PD.
Results: Treatment with 25-200μM sodium acetate (NaOAc) for 72h, promoted neurite outgrowth in a concentration dependent manner. However, treatment with 50μM NaOAc did not protect against neurite retraction induced by treatment with 10μM 6-OHDA for 72h. In contrast, a combination of SCFAs of 50μM NaOAc, 50μM Sodium Butyrate (NaBu) and 50µM Sodium Propionate (NaPro) did protect against 6-OHDA-induced decreases in neurite growth at 72h.
Conclusions: Our findings provide proof-of-principle that combinations of SCFAs may protect against degeneration induced by a neurotoxin in a human dopaminergic cell line in vitro. This rationalizes the further study of SCFAs as potential neuroprotective therapies for PD.