Physiology in Focus 2024, Newcastle Upon Tyne, İngiltere, 2 - 04 Temmuz 2024, ss.59
Autism Spectrum Disorders (ASD), are characterized with impairments in communication, lack of interest in social interactions and repetitive behaviours. Prenatal valproic acid (VPA) exposure, is used for modelling ASD like symptoms in rodents (1). Olfactory bonding with mother is crucial for a healthy social development and this is often tested with olfactory discrimination test (2). However, this test contains social cues only and therefore lacks the ability to distinguish whether observed differences occur due to social impairments or olfactory problems. This study aims to investigate olfactory response to social and non-social cues in prenatal VPA exposed rats.
Pregnant Wistar Albino rats received either 400mg/kg VPA (nMother: 3; nPup: 8) or saline (nMother: 3; nPup: 8) on embryonic day 12.5 intraperitoneally. Female pups were tested for olfactory discrimination (OD) on postnatal day 9 (P9), anxiety on P30 and olfaction without social cues on P40. OD test was performed for 3 minutes in plexiglass container with clean bedding on one side and bedding from mother cage on the other. Latency to reach either bedding was measured and rats were immediately returned to mothers. Anxiety was measured in open field. Total distance moved, velocity and frequency to entre border and centre zones were measured. Olfaction without social cues was tested for 5 minutes in a hole-board apparatus that consisted 16 holes with 2cm diameter. Rats were habituated to hole-board for 3 days prior testing to reduce stress. Food was removed from cages 8 hours prior testing. The test included a strawberry milk jar as a non-social olfactory cue under one of the centre holes. Latency of head digging into any holes was measured. Statistical analysis was performed with Student’s-t test on Sigma-Plot. The study was approved by Bursa UludaÄŸ University’s ethics committee (numbered: 2023-13/02).
Prenatal exposure to VPA impaired OD of mother/clean bedding. Latency to reach mother bedding was significantly increased in VPA group (p<0.022) whereas latency to reach any bedding showed no statistical difference between groups. In open field, VPA group showed decreased velocity (P<0.003) and frequency to entre both border (p<0.001) and centre zones (p=0.002). Control group had increased distance moved (p<0.001) and spent more time in centre areas compared to VPA group. In olfactory hole-board test, VPA group showed increased latency to dig their head into strawberry milk (p=0.003) whereas there was no significant difference between groups for latency of head digging into holes.
Olfaction is crucial in rodent survival. Inability to discriminate mother bedding from clean bedding suggests impairments in social communication. Results of open field test suggest increased anxiety in VPA group as expected from literature. For that reason, rats were habituated to hole-board. Insignificant difference in latency of head-digging shows that anxiety was eliminated. Within these results, this study suggests an impaired response to olfactory cues, whether social or non-social. This new set of information should be taken into account especially when sociability is assessed in models of ASD as inability to discriminate novel conspecific may occur merely as a result of a problem in olfaction.