Interaction of Brain-Derived Neurotrophic Factor Val66Met genotype and history of stress in regulation of prepulse inhibition in mice

van den Buuse, Maarten, Lee, John Juan Wen, and Jaehne, Emily J. (2018) Interaction of Brain-Derived Neurotrophic Factor Val66Met genotype and history of stress in regulation of prepulse inhibition in mice. Schizophrenia Research, 198. pp. 60-67.

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Abstract

The Brain-Derived Neurotrophic Factor (BDNF) Val66Met polymorphism results in reduced activity-dependent BDNF release and has been implicated in schizophrenia. However, effects of the polymorphism on functional dopaminergic and N-methyl-D-aspartate (NMDA) receptor-associated activity remain unclear. We used prepulse inhibition, a measure of sensorimotor gating which is disrupted in schizophrenia, and assessed the effects of acute treatment with the dopamine receptor agonist, apomorphine (APO). and the NMDA receptor antagonist, MK-801. We used adult humanized hBDNF(Val66Met) 'knockin' mice which express either the Val/Val, Val/Met or Met/Met genotype. An interaction of BDNF with stress was modelled by chronic young-adult treatment with corticosterone (CORT). At 1 or 3 mg/kg, APO had no effect in ValNal mice but significantly reduced PPI at the 100 ms inter-stimulus interval (ISI) in Val/Met and Met/Met mice. However, after CORT pretreatment, APO significantly reduced PPI in all genotypes similarly. At 0.1 or 0.25 mg/kg, MK-801 significantly disrupted PPI at the 100 ms ISI independent of genotype or CORY pretreatment. There were differential effects of APO and MK-801 on PPI at the 30 ms ISI and startle between the genotypes, irrespective of CORT pretreatment. These results show that the BDNF Val66Met Val/Met and Met/Met genotypes are more sensitive than the Val/Val genotype to the effect of APO on PPI. A history of stress, here modelled by chronic CORT administration, increases effects of APO in Val/Val mice.

Item ID: 55309
Item Type: Article (Research - C1)
ISSN: 1573-2509
Keywords: Brain-Derived Neurotrophic Factor, Prepulse inhibition, Dopamine, NMDA receptors, Stress, Corticosterone
Copyright Information: © 2017 Elsevier B.V. All rights reserved.
Funders: National Health and Medical Research Council of Australia (NHMRC), La Trobe University (LTU)
Date Deposited: 05 Sep 2018 09:35
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1117 Public Health and Health Services > 111706 Epidemiology @ 100%
Downloads: Total: 2
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