| Abstract No.: | C-C3076 |
| Country: | Canada |
| | |
| Title: | INTRAVENTRICULAR INFUSIONS OF THE ENTERIC SHORT CHAIN FATTY ACIDS, PROPIONIC AND BUTYRIC ACID, INDUCE BEHAVIOURAL, NEUROPATHOLOGICAL AND EPIGENETIC CHANGES IN RATS: POSSIBLE RELEVANCE TO AUTISM SPECTRUM DISORDERS |
| | |
| Authors/Affiliations: | 2 Derrick MacFabe*; 2 Lisa Tichenoff; 2 Roy Taylor; 2 Yalda Mohammad-Asef; 1 Edmund La Gamma; 1 Bistra Nankova;
1 New York Medical College, Valhalla, USA; 2 University of Western Ontario, London, ON, Canada
|
| | |
| Content: | Background: Diverse cell-cell interaction, neuroinflammatory and metabolic processes are implicated in the pathophysiology of autism spectrum disorders (ASDs). Environmental factors may activate these factors through epigenetic mechanisms. Propionic (PPA) or butyric acids (BA) are short chain fatty acids (SCFA) present in diet, and are also a product of enteric bacteria fermentation. SCFA have widespread effects on many of the above systems and a putative environmental trigger in ASD. We have shown that PPA can elicit consistent ASD related brain and behaviour changes in rats, while BA can induce genes implicated in catecholamine, enkephalin and CREB related processes in vitro.
Objective: To examine the effects of chronic intracerebroventricular infusions of SCFA on behaviour, neuropathology and gene expression in rats.
Materials and Method: Adult rats received infusions of pH 7.5 buffered PPA or BA (.26M) or PBS vehicle (0.1M) twice daily for 5 treatment days. Immediately following microinfusion, the animals were tested in a non novel automated open field (Versamax) and a variety of locomotor activity variables were assessed for 30 minutes.
After sacrifice brains were examined either neuropathologically for innate neuroinflammation, or via microarray analysis (Affymetrix Rat Genome GeneChip 230 2.0 microarrays/MetaCoreTM platform) for ASD related markers/genes.
Results: SCFA infusions increased locomotor activity. Both SCFA produced increased innate neuroinflammation (GFAP,IL-6) but only PPA produced activated microglia (CD68, IbA1). The alignment of gene content identified sets of genes unique for BA (274) and PPA (309). Comparison analyses of RNA identified a large number of genes (769) common for both groups, involved in canonical pathways/processes including cell development and differentiation, cytoskeleton organization and biogenesis, cell adhesion, inflammatory response, synaptic plasticity, cell-cell communication, neuroprotection and glutathione metabolism.
Conclusions: SCFA produce behavioural, neuropathological and epigenetic effects reminiscent of ASD when infused intraventricularly in rats, providing further evidence of a plausible dietary/gut/CNS link to this disorder
|
| | |
| Back |
|
