In utero exposure to valproic acid disrupts ascending projections to the central nucleus of the inferior colliculus from the auditory brainstem.

Autor: Zimmerman R; Department of Anatomy, Lake Erie College of Osteopathic Medicine, 1858 West Grandview Blvd, Erie, PA, 16504, USA., Smith A; Department of Anatomy, Lake Erie College of Osteopathic Medicine, 1858 West Grandview Blvd, Erie, PA, 16504, USA., Fech T; Department of Anatomy, Lake Erie College of Osteopathic Medicine, 1858 West Grandview Blvd, Erie, PA, 16504, USA., Mansour Y; Department of Anatomy, Lake Erie College of Osteopathic Medicine, 1858 West Grandview Blvd, Erie, PA, 16504, USA., Kulesza RJ Jr; Department of Anatomy, Lake Erie College of Osteopathic Medicine, 1858 West Grandview Blvd, Erie, PA, 16504, USA. rkulesza@lecom.edu.
Jazyk: angličtina
Zdroj: Experimental brain research [Exp Brain Res] 2020 Mar; Vol. 238 (3), pp. 551-563. Date of Electronic Publication: 2020 Jan 25.
DOI: 10.1007/s00221-020-05729-7
Abstrakt: Prenatal exposure to the antiepileptic valproic acid (VPA) is associated with an increased risk of autism spectrum disorder (ASD) in humans. Accordingly, in utero exposure to VPA is a validated and biologically relevant animal model of ASD. The majority of individuals with ASD exhibit some degree of auditory dysfunction, ranging from deafness to hypersensitivity. Animals exposed to VPA in utero have abnormal tonotopic maps and responses in the cerebral cortex and hyperactivation, hypoplasia, abnormal neuronal morphology and reduced calcium binding protein expression throughout the auditory brainstem nuclei. Further, our previous work suggests that GABAergic neuronal populations may be more severely impacted by in utero VPA exposure. However, the axonal projection patterns of brainstem nuclei to the inferior colliculus (IC) have not been investigated in VPA-exposed animals. Herein, we use stereotaxic injections of the retrograde tracer Fast Blue into the central nucleus of the IC (CNIC) and examine the proportions of retrogradely labeled neurons in the nuclei of the lateral lemniscus, superior olivary complex and cochlear nuclei. Our results indicate that not only are there fewer neurons in the auditory brainstem after VPA exposure, but also that fewer neurons are retrogradely labeled from the CNIC. Together, our results indicate that in utero VPA exposure may result in altered patterns of input to the auditory midbrain.
Databáze: MEDLINE