Auditory Brainstem Response (ABR) Abnormalities Across the Life Span of Rats Prenatally Exposed to Alcohol

Abstract

Background Fetal Alcohol Syndrome is a leading cause of neurodevelopmental impairments (NDI) in developed countries. Sensory deficits can play a major role in NDI, yet few studies have investigated the effects of prenatal alcohol exposure on sensory function. In addition, there is a paucity of information on the life-long effects of prenatal alcohol exposure. Thus, we sought to investigate the effects of prenatal alcohol exposure on auditory function across the life span in an animal model. Based on prior findings with prenatal alcohol exposure and other forms of adverse prenatal environments, we hypothesized that animals prenatally exposed to alcohol would show an age-dependent pattern of (A) hearing and neurological abnormalities as post-weanling pups, (B) a substantial dissipation of such abnormalities in young adulthood, and (C) a resurgence of such abnormalities in middle-aged adulthood. Method Pregnant rats were randomly assigned to an untreated control (CON), a pair-fed control (PFC) or an alcohol treated group (ALC). The ALC dams were gavaged with 6 mg/kg alcohol daily from gestation day (GD) 6 to 21. The PFC dams were gavaged daily from GD6-21 with an isocaloric and isovolumetric water-based solution of Maltose-Dextrins and pair-fed to the ALC dams. The CON dams were the untreated group to which the ALC and CON groups were compared. Hearing and neurological functions in the offspring were assessed with the Auditory Brainstem Response (ABR) at the postnatal ages of 22, 220 and 520 days of age. Results & Conclusions In accord with our hypothesis, ABR abnormalities were first observed in the post-weanling pups, largely dissipated in young adulthood, and then resurged in middle-aged adulthood. This age-related pattern suggests that the ALC pups had a developmental delay that dissipated in young adulthood and an enhanced age-related deterioration that occurred in middle-aged adulthood. Such a pattern is consistent with the fetal programming hypothesis of adult-onset diseases (the Barker Hypothesis). Our findings have important clinical implications for the assessment and management of (A) childhood hearing disorders and their co-morbidities (i.e., speech-and-language, learning, and attention deficit disorders) and (B) enhanced age-related hearing and neurological degeneration in middle-aged adulthood that can result from prenatal alcohol exposure. We recommend hearing evaluation be a part of any long-term follow-up for FAS patients and patients exposed to any adverse prenatal environment.

‘Ecstasy’ enhances noise-induced hearing loss

“…Binaural ‘open field’ tone pips in the ascending order of 2, 4, 8, 16 and 32 kHz were delivered through either a headphone (TDH-39P, Telephonics Corporation, Farmingdale, NY) for the 2–8 kHz tone pips or a tweeter speaker (Super Tweeter, Tandy Corporation, Fort Worth, TX) for the 16 and 32 kHz tone pips that were placed in front of the animal (rise/fall time = 0.5 ms, plateau = 10 ms, polarity = alternating, repetition rate = 19/s). These tone pip frequencies cover the range of greatest hearing sensitivity for a rat and are comparable to the range tested in other recent rat ABR or mouse auditory neurophysiology studies, permitting an assessment of frequency-dependent effects (Chen & Henderson, 2009; Church et al, 2004; Church et al, 2012; Henry, 2003; Tanaka et al, 2003). …”

“…Presenting stimuli at fast repetition rates constitutes an auditory stressor test that can reveal neurological abnormalities (e.g., poor neural synchrony) that may not be present when stimuli are presented at a slow repetition rate (Church et al, 2012; Santos et al, 2004; Starr et al, 2001). Thus, Experiment #2 used this stressor test to see if MDMA treatment interacted with the stimulus repetition rate.…”

“…In comparison, the human ABR is labeled with Roman numerals with the major neurogenerators believed to be the distal auditory nerve (I), proximal auditory nerve (II), cochlear nucleus (III), superior olivary complex (IV), and the termination of the contralateral lateral lemniscus in the inferior colliculus (V) (Moller et al, 1995). The latency of each wave is measured from the stimulus onset to the peak of the wave, usually including an acoustic travel time between the speaker or earphone diaphragm and the animal’s ear (Church et al, 1984; Church et al, 2004; Church et al, 2012). In our lab, we measure the amplitudes as the height between the wave’s positive peak and the following negative trough (i.e., P1-N1, P2-N2, P3-N3, P4-N4 and P5-N5).…”

Alcohol-Induced Developmental Origins of Adult-Onset Diseases

“…This study exemplifies an important feature of alcohol exposure during pregnancy, that is in addition to impacting the mother and fetus, the fetal germline is vulnerable. Neurobiological : Rats were administered alcohol (6 mg/kg) and were assessed for auditory brain stem response at 22 days, 7 months, and 17 months after birth; in accordance with the Barker hypothesis, the authors reported developmental delay that dissipated at 7 months, and enhanced deficits at 17 months, thus recommending long-term follow up of prenatally alcohol-exposed kids (Church et al, 2012). Nutrient homeostasis : Alcohol-exposed rats were studied up to 14 months after birth, and male rats specifically demonstrated significantly higher fasting serum triglyceride levels.…”

Speech development delay in a child with foetal alcohol syndrome

“…Foetal alcohol syndrome is characterised by congenital malformations associated with impaired hearing. There are four types of auditory disorders found in FAS, namely: delay in the development of auditory maturation, sensory hearing loss -teratogenic effect of alcohol on the auditory system causes damage to the inner ear cells in the embryo [11], hearing loss caused by recurrent serious otitis of the middle ear, and central hearing loss [12].…”