Altered neuronal activity in the auditory brainstem following sound stimulation in thalidomide-induced autism model rats

概要

Introduction (尊論）
Autism is a neurodevelopmental disorder, characterized by difficulties in social interaction, communication, and restricted and repetitive behavior. Frequently, autistic individuals also can present sensory abnormalities. Among these, auditory hypersensitivity is commonly observed in autistic individuals. The auditory pat~way is organized by sound frequencies from the cochlea to the auditory cortex. In other words, specific neurons are known to respond to only specific frequencies. Thus, in auditory hypersensitivity, alterations in auditory brainstem has been suspected. However, the mechanisms of autism and auditory hypersensitivity are still known.

Background (背景）
We have generated an autism model rat by prenatal thalidomide exposure to pregnant rats, in which serotonin dysfunction and alterations in the auditory brainstem has been observed. This method is based in a study in which thalidomide intake by pregnant women on early embryonic days led to a high ratio of autistic newborns. Also, the period of ear formation in humans is between embryonic days 20 to 24, which correspond to embryonic days 9 and 10 in rats.

Objectives (目的）
To elucidate the molecular mechanisms of auditory hypersensitivity, we investigate whether abnormal response occurs in the brainstem following sound stimulus in autism model rats. By elucidating these mechanisms, the quality of life of autistic patients can be improved.

Methods (方法）
Pregnant rats were exposed to thalidomide on Embryonic days 9 and 10 to prepare the autism model rats. On postnatal day 49 to 51, the pups were placed in a sound attenuated box and remained there for 30 minutes to habituate. Then, they were exposed to 16-kHz sound stimulus for one hour. The brains were subjected to conventional immunohistochemical technique and the neuronal activity of these animals were observed using anti-c-Fos antibody.

Results (結果）
Following sound stimulation of 16 kHz, control :rats showed c-Fos-positive neurons in the specific area of the medial nucleus of the trapezoid body, which was consistent to the reported region in previous studies. On the other hand, in the thalidomide-exposed animals, c-Fospositive neurons were observed not restricted in that area, but was expanded beyond the 16 kHz-responsive area. Also, increased number of c-Fos-positive neurons was observed in the auditory brainstem of autism model rats compared to control rats. These results suggest that the area activated by 16 kHz sound stimulus seems to differ between control and autistic rats and also it changes the responsive area.

Consideration (考察）
Sound response system differed between control and thalidomide-exposed animals. This suggests that prenatal thalidomide might cause altered processing of auditory stimulus, contributing to auditory hypersensitivity in autism.

Conclusion (結論）
Investigating the molecular mechanisms of auditory hypersensitivity can help improve the quality of life of autistic individuals.