Akademik Veri Yönetim Sistemi
Breakthroughs in Understanding Natural Behaviour and its Neural Underpinnings, Manchester, İngiltere, 10 - 11 Eylül 2024, ss.14
Autism Spectrum Disorders (ASD), are characterized with impairments in communication, lack of interest in social interactions and repetitive behaviours. Even though the 4–5:1 male-to-female ratio of diagnosis is reported, the inclusion of both sexes in research is important, especially for the risk of misdiagnosing females. Prenatal valproic acid (VPA) exposure is used to model ASD-like symptoms in rodents (1). The prevalence of ASD in children exposed to VPA during pregnancy is reported to be 1:1 male-to-female ratio (2). This study aims to investigate how both males and females exhibit ASD-like symptoms after prenatal VPA exposure.
Pregnant Wistar Albino rats received either 400mg/kg VPA (nMother:4; nFemale Pup:8, nMale Pup:8) or saline (nMother:4; nFemale Pup:8, nMale Pup:8) on embryonic day 12.5 intraperitoneally. Pups were tested for olfactory discrimination (OD) on postnatal day 9 (P9). Latency to reach mother bedding was measured. Three-Chamber Social Interaction test (TCSI) was used to assess sociability on P25. Time spent in a chamber containing a stranger rat was measured. Locomotion was assessed in Open Field (OF) on P30. Total distance moved and immobility was measured. Anxiety was measured in Elevated Plus Maze (EPM) on P32. The frequency to entre open/closed arms was measured. Hole-Board apparatus was used to assess exploratory behaviour on P35. The frequency of head-dipping was measured. Statistical analysis was performed with Two-Way ANOVA test on Sigma-Plot. The study was approved by Bursa UludaÄŸ University’s ethics committee (numbered:2024-01/08).
Pups that were prenatally exposed to VPA showed differences compared to the control group in both sexes. Latency to reach mother bedding was significantly increased in both females and males of the VPA group (p<0.001; p<0.001). There was not a significant interaction between sex and VPA exposure (F(1.31)=0.515, p=0.479). In the TCSI test, both females and males of the VPA group spent significantly less time in the chamber containing a stranger rat (p<0.001; p<0.001). Interaction between sex and VPA exposure was significant (F(1.31)=43.175, p<0.001). Both females and males of the VPA group travelled significantly less (p<0.001; p<0.001) and spent significantly more time immobile (p=0.011; p=0.026) in OF. There was not a significant interaction between sex and VPA exposure in distance moved (F(1.31)=0,189, p=0.667) and immobile time (F(1.31)=0.0734, p=0.788). In EPM, VPA females had a higher ratio of entry to open arms compared to control females (p<0.001), whereas VPA males had a lower ratio of entry to open arms compared to control males (p=0.002). Interaction between sex and VPA exposure was significant (F(1.31)=38.323, p<0.001). The frequency of head-dipping was significantly lower in both females and males of the VPA group (p<0.001; p<0.001). Interaction between sex and VPA exposure was significant (F(1.31)=34.300, p<0.001).
This study suggests that prenatal exposure to VPA induces ASD-like symptoms in both male and female rats. Notable differences between control and VPA groups were reported in performed behavioural tests, with some of these differences being sex-dependent. Expression of autism varies in females, which often causes underdiagnosis and leads to loss of effectiveness of treatment. Therefore, the inclusion of both sexes in research is crucial and should be emphasized.