Master of Science
The enteric bacterial metabolite, propionic acid (PPA), elicits physiological and behavioural changes in rodents reminiscent of autism spectrum disorder (ASD). This includes abnormal sensory processing and social behaviour. ASD may contribute to social deficits through impaired habituation; therefore, the present study examined the effects of intraperitoneal PPA on the habituation to social and non-social odours. Adult male rats were injected daily with PPA or the vehicle control, and for 3 days, habituated to a conspecific odour or vanilla extract for 10 minutes. On day 4, rats were exposed to a novel conspecific odour or almond extract for 10 minutes to observe dishabituation. Behaviours were measured in the open-field and analyzed via an automated system and by the manual scoring of video-recordings. Results from both scoring methods strongly correlated with one another. PPA treatment significantly increased repetitive behaviours and hypoactivity. Drug and odour had no significant effects on odour habituation, although PPA non-social rats displayed reduced habituation for entries into the odour quadrant and sniffing. Group differences were insignificant. No dishabituation to the odour was observed in all groups. However, an insignificant, subtle reduction in dishabituation to the open-field was seen in PPA groups for total distance travelled. PPA may influence odour discrimination in rodents and contribute to sensory habituation deficits in ASD. Differences in body temperature and weight post-injection were measured to monitor a potential sickness response from the bacterial by-product. Results for PPA rats did not differ from controls, suggesting that PPA exerts its effects through other mechanisms.
Summary for Lay Audience
Disturbances involving enteric metabolites highlight the gut-brain axis, as they may play a role in the etiology of autism spectrum disorders (ASDs). The gut bacterial by-product, propionic acid (PPA), is of interest as an etiological factor in ASD, as it can cross the blood-brain barrier and affect central nervous system functioning. PPA can elicit ASD-like symptoms in rodents including abnormal social behaviour, repetitive movements, sensory processing deficits, and hypoactivity. ASD may contribute to social deficits through impaired habituation to sensory and social stimuli, therefore, the present study examined the effects of systemic PPA injections in adult male rats on habituation to social and non-social odors. Habituation is expressed when there is a diminished response to a stimulus after repeated exposure. For rats with properly functioning olfactory systems, habituation occurs when an odour stimulus is sniffed less often over time. Dishabituation occurs when a novel odour is introduced, and an increase in odour investigation is observed.
Rats were injected daily with PPA or the control, phosphate buffered saline. Behaviours were detected in the open-field via an automated system and by video-recordings. Results from both scoring methods strongly correlated with one another. Rats habituated to same social or non-social odour for 10 minutes for 3 consecutive days. On the 4th day, rats were exposed to a different social or non-social odour to observe dishabituation.
PPA was effective, as treatment groups displayed significantly more hypoactivity and repetitive behaviours compared to controls. Drug and odour had no significant effects on odour habituation, however PPA non-social rats habituated the least. Group differences were insignificant. No groups showed significant dishabituation to the novel odours, although only PPA treated rats showed a reduction in odour investigation. Group differences were also insignificant. Results suggest that PPA may have a general effect on odour discrimination in rodents, and that it may contribute to social deficits in ASD by impairing habituation to sensory cues.
Body temperature and weight were monitored throughout the experiment to see if the bacterial product induced sickness. Results from PPA treated rats did not differ from controls, suggesting PPA exerts its effects through other mechanisms.
Tyson, Cashmeira-Dove P., "The Effect of Propionic Acid on the Habituation to Social and Non-social Odour Cues in Adult Male Rats" (2022). Electronic Thesis and Dissertation Repository. 8875.
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