scholarly journals Developmental PCB exposure disrupts synaptic transmission and connectivity in the rat auditory cortex, independent of its effects on peripheral hearing threshold

2020 ◽  
Author(s):  
Christopher M. Lee ◽  
Renee N. Sadowski ◽  
Susan L. Schantz ◽  
Daniel A. Llano

AbstractPolychlorinated biphenyls (PCBs) are enduring environmental toxicants and exposure is associated with neurodevelopmental deficits. The auditory system appears particularly sensitive, as previous work has shown that developmental PCB exposure causes both hearing loss and gross disruptions in the organization of the rat auditory cortex. However, the mechanisms underlying PCB-induced changes are not known, nor is it known if the central effects of PCBs are a consequence of peripheral hearing loss. Here, we study changes in both peripheral and central auditory function in rats with developmental PCB exposure using a combination of optical and electrophysiological approaches. Female rats were exposed to an environmental PCB mixture in utero and until weaning. At adulthood, auditory brainstem responses were measured, and synaptic currents were recorded in slices from auditory cortex layer 2/3 neurons. Spontaneous and miniature inhibitory postsynaptic currents (IPSCs) were more frequent in PCB-exposed rats compared to controls and the normal relationship between IPSC parameters and peripheral hearing was eliminated in PCB-exposed rats. No changes in spontaneous EPSCs were found. Conversely, when synaptic currents were evoked by laser photostimulation of caged-glutamate, PCB exposure did not affect evoked inhibitory transmission, but increased the total excitatory charge, the number and distance of sites that evoke a significant response. Together, these findings indicate that early developmental exposure to PCBs causes long-lasting changes in both inhibitory and excitatory neurotransmission in the auditory cortex that are independent of peripheral hearing changes, suggesting the effects are due to the direct impact of PCBs on the developing auditory cortex.Significance StatementThe mechanisms by which developmental exposure to polychlorinated biphenyls (PCBs) disrupt the central nervous system are not yet known. Here we show that developmental PCB exposure is associated with long-lasting dysregulation of both excitatory and inhibitory neurotransmission in the rodent brain. We further find that, unlike controls, synaptic parameters in the auditory cortex of PCB-exposed rats are independent of peripheral hearing changes. These data suggest that PCB-related changes in the auditory cortex are independent of their effects on the auditory periphery and that PCB exposure may disrupt the plastic mechanisms needed to restore normal processing in the auditory cortex after peripheral hearing loss.

Author(s):  
F. Matin ◽  
S. Haumann ◽  
W. Roßberg ◽  
D. Mitovska ◽  
T. Lenarz ◽  
...  

Abstract Purpose The objective of this study was to investigate the auditory pathway maturation monitored by auditory brainstem responses (ABR) in infants with hearing loss during the first year of life. ABR were used to estimate hearing thresholds and the effect of early intervention strategies using hearing aids (HA). Methods Click-evoked ABRs were measured in 102 infants aged from 0 to 12 months to determine their individual auditory threshold. Early therapy intervention was recommended before 12 months of age and analyzed. To evaluate the effect of hearing amplification on auditory maturation, different subgroups of infants with moderate hearing loss were analyzed and the auditory pathway maturation was determined based on IPL I–V shortening. Results Overall, 110 ears (54.0% of 204 ears) with mild to profound HL showed threshold changes of 10 dB up to 60 dB in the follow-up ABR testing. HA were prescribed at the age of 3.8 ± 3.9 months. Cochlear implantation (CI) was performed in cases of repeated profound HL at the age of 9.9 months ± 4.5 months. A significant shortening of IPL I–V in all subgroups of infants (with and without risk factors) who received HA was shown and assumed auditory pathway maturation. Conclusion An early intervention using optimally fitted HA influenced auditory pathway maturation and may lead to improvements of hearing thresholds during the first year of life in infants. This study underscores the importance of not only providing HAs to infants, but also controlling for hearing threshold changes ensuring that HAs provide the optimal level of intervention or CI is indicated.


2017 ◽  
Vol 7 (2) ◽  
Author(s):  
Belde Culhaoglu ◽  
Selim S. Erbek ◽  
Seyra Erbek ◽  
Evren Hizal

Acoustic trauma is a common reason for hearing loss. Different agents are used to prevent the harmful effect of acoustic trauma on hearing. The aim of this study was to evaluate the potential preventive effect of <em>Nigella sativa</em> (black cumin) oil in acoustic trauma. Our experimental study was conducted with 20 Sprague Downey female rats (mean age, 12 months; mean weight 250 g). All of the procedures were held under general anesthesia. Following otoscopic examinations, baseline-hearing thresholds were obtained using auditory brainstem responses (ABR). To create acoustic trauma, the rats were then exposed to white band noise of 4 kHz with an intensity level of 107 dB in a soundproof testing room. On Day 1 following acoustic trauma, hearing threshold measurements were repeated. The rats were divided into two groups as the study group (n: 10) and the controls (n: 10). 2 mL/kg/day of <em>Nigella sativa</em> oil was given to the rats in the study group orally. On Day 4 following acoustic trauma, ABR measurements were repeated again. There was no difference between the baseline hearing thresholds of the rats before acoustic trauma (P&gt;0.005). After the acoustic trauma, hearing thresholds were increased and there was no significant statistically difference between the hearing thresholds of the study and control groups (P=0.979). At the 4<sup>th</sup> day following acoustic trauma, hearing thresholds of the rats in control group were found to be higher than those in the study group (P=0.03). Our results suggest that <em>Nigella sativa</em> oil has a protective effect against acoustic trauma in early period. This finding should be supported with additional experimental and clinical studies, especially to determine the optimal dose, duration and frequency of potential <em>Nigella sativa</em> oil therapy.


eNeuro ◽  
2021 ◽  
Vol 8 (1) ◽  
pp. ENEURO.0321-20.2021
Author(s):  
Christopher M. Lee ◽  
Renee N. Sadowski ◽  
Susan L. Schantz ◽  
Daniel A. Llano

2021 ◽  
Vol 15 ◽  
Author(s):  
Kimberly P. Keil Stietz ◽  
Sunjay Sethi ◽  
Carolyn R. Klocke ◽  
Tryssa E. de Ruyter ◽  
Machelle D. Wilson ◽  
...  

While many neurodevelopmental disorders (NDDs) are thought to result from interactions between environmental and genetic risk factors, the identification of specific gene-environment interactions that influence NDD risk remains a critical data gap. We tested the hypothesis that polychlorinated biphenyls (PCBs) interact with human mutations that alter the fidelity of neuronal Ca2+ signaling to confer NDD risk. To test this, we used three transgenic mouse lines that expressed human mutations known to alter Ca2+ signals in neurons: (1) gain-of-function mutation in ryanodine receptor-1 (T4826I-RYR1); (2) CGG-repeat expansion in the 5′ non-coding portion of the fragile X mental retardation gene 1 (FMR1); and (3) a double mutant (DM) that expressed both mutations. Transgenic and wildtype (WT) mice were exposed throughout gestation and lactation to the MARBLES PCB mix at 0.1, 1, or 6 mg/kg in the maternal diet. The MARBLES mix simulates the relative proportions of the twelve most abundant PCB congeners found in serum from pregnant women at increased risk for having a child with an NDD. Using Golgi staining, the effect of developmental PCB exposure on dendritic arborization of pyramidal neurons in the CA1 hippocampus and somatosensory cortex of male and female WT mice was compared to pyramidal neurons from transgenic mice. A multilevel linear mixed-effects model identified a main effect of dose driven by increased dendritic arborization of cortical neurons in the 1 mg/kg PCB dose group. Subsequent analyses with genotypes indicated that the MARBLES PCB mixture had no effect on the dendritic arborization of hippocampal neurons in WT mice of either sex, but significantly increased dendritic arborization of cortical neurons of WT males in the 6 mg/kg PCB dose group. Transgene expression increased sensitivity to the impact of developmental PCB exposure on dendritic arborization in a sex-, and brain region-dependent manner. In conclusion, developmental exposure to PCBs present in the gestational environment of at-risk humans interfered with normal dendritic morphogenesis in the developing mouse brain in a sex-, genotype- and brain region-dependent manner. Overall, these observations provide proof-of-principle evidence that PCBs interact with heritable mutations to modulate a neurodevelopmental outcome of relevance to NDDs.


Author(s):  
Nam-Jeong Kim ◽  
Hyoung-Ouk Park ◽  
Chang-Sun Sim ◽  
Choong-Ryeol Lee ◽  
Young-Joo Kwon ◽  
...  

2002 ◽  
Vol 13 (05) ◽  
pp. 236-245 ◽  
Author(s):  
Gary Rance ◽  
Field Rickards

This retrospective study examines the relationship between auditory steady-state evoked potential (ASSEP) thresholds determined in infancy and subsequently obtained behavioral hearing levels in children with normal hearing or varying degrees of sensorineural hearing loss. Overall, the results from 211 subjects showed that the two test techniques were highly correlated, with Pearson r values exceeding .95 at each of the audiometric test frequencies between 500 and 4000 Hz. Analysis of the findings for babies with significant hearing loss (moderate to profound levels) showed similar threshold relationships to those obtained in previous studies involving adults and older children. The results for infants with normal or near-normal hearing did, however, differ from those reported for older subjects, with behavioral thresholds typically 10 to 15 dB better than would have been predicted from their ASSEP levels.


PEDIATRICS ◽  
2010 ◽  
Vol 127 (1) ◽  
pp. e39-e46 ◽  
Author(s):  
E. Henderson ◽  
M. A. Testa ◽  
C. Hartnick

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