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

Abstract

Auditory hypersensitivity in autism is frequently observed in clinics. Dysfunction in the auditory brainstem has been suspected. We have established autism model rats using prenatal thalidomide exposure. Here we investigated whether abnormal response occurs in the brainstem following sound stimulus in autism model rats. Autism model rats were prepared by prenatal exposure to thalidomide on embryonic days 9 and 10 in pregnant rats. Then, the animals were exposed to 16‐kHz pure tone auditory stimulus and c‐Fos immunostaining was performed to examine the neuronal activity on postnatal day 49 to 51. Following sound stimulus, increased number of c‐Fos‐positive neurons was observed in the medial nucleus of the trapezoid body of autism model rats compared with the control rats. These results suggest that prenatal thalidomide might cause altered processing of auditory stimulus, leading to the characteristics of auditory hypersensitivity in autism.

A Systematic Review of Brainstem Contributions to Autism Spectrum Disorder

“…THAL-exposed rats had a decreased SOC immunoreactivity and smaller MNTB compared to control (Ida-Eto et al, 2017 ). Another study exposed rats to 16-kHz pure tone auditory stimulus and c-Fos immunostaining (Tsugiyama et al, 2020 ). THAL rats had an increased number of c-Fos-positive neurons in MNTB compared to the control (Tsugiyama et al, 2020 ).…”

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“…VPA-exposed animals have fewer and more dysmorphic VCN (Zimmerman et al, 2018) and SOC (Lukose et al, 2011;Zimmerman et al, 2018) neurons. SOC abnormalities are also seen in the Fmr1 KO model (Ruby et al, 2015;Garcia-Pino et al, 2017;Rotschafer and Cramer, 2017) and THAL-exposed rats (Ida-Eto et al, 2017;Tsugiyama et al, 2020). The morphometric malformation of SOC components in VPA-exposed rats (Lukose et al, 2011) were consistent with malformation in SOC of autistic brains (Kulesza et al, 2011).…”

“…Morphological and structural changes in brainstem size and shape of key brainstem nuclei are observed in both autistic humans (Gaffney et al, 1988;Hashimoto et al, 1989Hashimoto et al, , 1992aHashimoto et al, ,b, 1993aHashimoto et al, ,b, 1995Herbert et al, 2003;Craig et al, 2007;Kulesza and Mangunay, 2008;Jou et al, 2009;Toal et al, 2010;Kulesza et al, 2011;Fredo et al, 2014;Wegiel et al, 2014;Hanaie et al, 2016;Andersson et al, 2020) and in rodent models of autism (Lukose et al, 2011;Ruby et al, 2015;Garcia-Pino et al, 2017;Ida-Eto et al, 2017;Rotschafer and Cramer, 2017;Zimmerman et al, 2018Zimmerman et al, , 2020Tsugiyama et al, 2020). Moreover, functional abnormalities are also observed in autistic humans (Tanguay et al, 1982;Ming et al, 2005;Jou et al, 2009;Källstrand et al, 2010;Magliaro et al, 2010;Dabbous, 2012;Travers et al, 2015;Ververi et al, 2015;Hanaie et al, 2016;Claesdotter-Knutsson et al, 2019;Granovetter et al, 2019) and rodent models of autism (Strata et al, 2005;Rotschafer et al, 2015;Scott et al, 2018;Felix et al, 2019).…”

“…THAL-exposed rats had a decreased SOC immunoreactivity and smaller MNTB compared to control (Ida-Eto et al, 2017). Another study exposed rats to 16-kHz pure tone auditory stimulus and c-Fos immunostaining (Tsugiyama et al, 2020). THAL rats had an increased number of c-Fos-positive neurons in MNTB compared to the control (Tsugiyama et al, 2020).…”

“…Another study exposed rats to 16-kHz pure tone auditory stimulus and c-Fos immunostaining (Tsugiyama et al, 2020). THAL rats had an increased number of c-Fos-positive neurons in MNTB compared to the control (Tsugiyama et al, 2020).…”