Zinnamon, Fhatarah A;
Harrison, Freya G;
Wenas, Sandra S;
Liu, Qing;
Wang, Kuan Hong;
Linden, Jennifer F;
(2022)
Increased central auditory gain and decreased parvalbumin-positive cortical interneuron density in the Df1/+ mouse model of schizophrenia correlate with hearing impairment.
Biological Psychiatry Global Open Science
10.1016/j.bpsgos.2022.03.007.
(In press).
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Abstract
Background Hearing impairment is a risk factor for schizophrenia. Patients with 22q11.2 Deletion Syndrome (22q11.2DS) have a 25-30% risk of schizophrenia, and up to 60% also have varying degrees of hearing impairment, primarily from middle ear inflammation. The Df1/+ mouse model of 22q11.2DS recapitulates many features of the human syndrome, including schizophrenia-relevant brain abnormalities and high inter-individual variation in hearing ability. However, the relationship between brain abnormalities and hearing impairment in Df1/+ mice has not been examined. Methods We measured auditory brainstem responses (ABRs), cortical auditory evoked potentials, and/or cortical parvalbumin-positive (PV+) interneuron density in over 70 adult mice (32 Df1/+, 39 wild-type). We also performed longitudinal ABR measurements in an additional 20 animals (13 Df1/+, 7 wild-type) from 3 weeks of age. Results Electrophysiological markers of central auditory excitability were elevated in Df1/+ mice. PV+ interneurons, which are implicated in schizophrenia pathology, were reduced in density in auditory cortex but not secondary motor cortex. Both auditory brain abnormalities correlated with hearing impairment, which affected approximately 60% of adult Df1/+ mice and typically emerged before 6 weeks of age. Conclusions In the Df1/+ mouse model of 22q11.2DS, abnormalities in central auditory excitability and auditory cortical PV+ immunoreactivity correlate with hearing impairment. This is the first demonstration of cortical PV+ interneuron abnormalities correlating with hearing impairment in a mouse model of either schizophrenia or middle ear inflammation.
| Type: | Article |
|---|---|
| Title: | Increased central auditory gain and decreased parvalbumin-positive cortical interneuron density in the Df1/+ mouse model of schizophrenia correlate with hearing impairment |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.bpsgos.2022.03.007 |
| Publisher version: | https://doi.org/10.1016/j.bpsgos.2022.03.007 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third-party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | 22q11.2 Deletion Syndrome, diGeorge Syndrome, Velocardiofacial Syndrome, auditory cortex, parvalbumin-positive interneurons, auditory evoked potentials |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > The Ear Institute UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10145995 |
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