ORCID
https://orcid.org/0000-0002-7229-7136
Department
Biological Sciences
Year of Study
3
Full-time or Part-time Study
Full-time
Level
Postgraduate
Presentation Type
Oral Presentation
Supervisor
Dr Caitriona Guinane
Supervisor
Prof Gerard O’Keeffe
Supervisor
Dr Louise Collins
Abstract
Background
Parkinson’s disease (PD) is a neurodegenerative disorder characterized by dopaminergic neuron degeneration. This degeneration is partly driven by over expression of α-synuclein (α-syn) and development of α-syn aggregates known as Lewy bodies throughout the substantia nigra. As well as motor dysfunction, PD presents with several chronic gastrointestinal comorbidities, which cause a decline of gut microbial diversity and microbially derived short chain fatty acids (SCFAs). Recent in vivo studies have shown SCFAs to be neuroprotective in various degenerative disease states, suggesting that SCFAs may protect against dopaminergic degeneration.
Methods
Human neuroblastoma SH-SY5Y cells were used 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 dopaminergic neurotoxin, 6-hydroxydopamine (6-OHDA) as an in vitro model of PD. Furthermore, we examined the effects of a SCFA combination treatment in SH-SY5Y cells transfected to overexpress wild type a-syn (WT α-syn) as a secondary model of PD related degeneration.
Results
Concurrent sodium acetate (NaOAc) treatment (25 µM – 200 uM) for 72 h, promoted neurite outgrowth in a concentration dependent manner. However, treatment with 50 μM NaOAc did not protect against neurite retraction induced by 10 μM 6-OHDA treatment for 72 h. Conversely, a SCFA combination of 50 μM NaOAc, 50 μM Sodium Butyrate and 50 µM Sodium Propionate did protect against 6-OHDA-induced decreases in neurite growth at 72 h. Similarly, the transfected model of SH-SY5Y cells showed that this concurrent SCFA combination treatment at 50 μM protected against WT α-syn associated neurite retraction at the 72 h timepoint.
Conclusions
These findings provide proof-of-principle that SCFAs may protect against degeneration induced by a neurotoxin and a-syn overexpression in the SH-SY5Y cell line in vitro. This rationalizes the further study of SCFAs and SCFA producing microbes as potential neuroprotective therapies for PD.
Keywords:
Short chain fatty acids(SCFAs), 6-OHDA, SHSY5Y cells, neurite length, Wild type alpha synuclein
Start Date
2-11-2023 12:00 PM
End Date
2-11-2023 12:15 PM
Recommended Citation
Morris, Alex, "Short chain fatty acid combination treatment protects against 6-OHDA and WT α-synuclein induced decreases in neurite growth in in vitro models of Parkinson’s disease." (2023). ORBioM (Open Research BioSciences Meeting). 4.
https://sword.cit.ie/orbiom/2023/oral2/4
Included in
Cell Biology Commons, Molecular and Cellular Neuroscience Commons, Organismal Biological Physiology Commons, Other Neuroscience and Neurobiology Commons
Short chain fatty acid combination treatment protects against 6-OHDA and WT α-synuclein induced decreases in neurite growth in in vitro models of Parkinson’s disease.
Background
Parkinson’s disease (PD) is a neurodegenerative disorder characterized by dopaminergic neuron degeneration. This degeneration is partly driven by over expression of α-synuclein (α-syn) and development of α-syn aggregates known as Lewy bodies throughout the substantia nigra. As well as motor dysfunction, PD presents with several chronic gastrointestinal comorbidities, which cause a decline of gut microbial diversity and microbially derived short chain fatty acids (SCFAs). Recent in vivo studies have shown SCFAs to be neuroprotective in various degenerative disease states, suggesting that SCFAs may protect against dopaminergic degeneration.
Methods
Human neuroblastoma SH-SY5Y cells were used 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 dopaminergic neurotoxin, 6-hydroxydopamine (6-OHDA) as an in vitro model of PD. Furthermore, we examined the effects of a SCFA combination treatment in SH-SY5Y cells transfected to overexpress wild type a-syn (WT α-syn) as a secondary model of PD related degeneration.
Results
Concurrent sodium acetate (NaOAc) treatment (25 µM – 200 uM) for 72 h, promoted neurite outgrowth in a concentration dependent manner. However, treatment with 50 μM NaOAc did not protect against neurite retraction induced by 10 μM 6-OHDA treatment for 72 h. Conversely, a SCFA combination of 50 μM NaOAc, 50 μM Sodium Butyrate and 50 µM Sodium Propionate did protect against 6-OHDA-induced decreases in neurite growth at 72 h. Similarly, the transfected model of SH-SY5Y cells showed that this concurrent SCFA combination treatment at 50 μM protected against WT α-syn associated neurite retraction at the 72 h timepoint.
Conclusions
These findings provide proof-of-principle that SCFAs may protect against degeneration induced by a neurotoxin and a-syn overexpression in the SH-SY5Y cell line in vitro. This rationalizes the further study of SCFAs and SCFA producing microbes as potential neuroprotective therapies for PD.