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       Life-Course Contribution of Prenatal Stress in Regulating the Neural Modulation Network Underlying the Prepulse Inhibition of the Acoustic Startle Reflex in Male Alzheimer’s Disease Mice

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          Abstract

          The prepulse inhibition (PPI) of the acoustic startle reflex (ASR), as an index of sensorimotor gating, is one of the most extensively used paradigms in the field of neuropsychiatric disorders. Few studies have examined how prenatal stress (PS) regulates the sensorimotor gating during the lifespan and how PS modifies the development of amyloid-beta (Aβ) pathology in brain areas underlying the PPI formation. We followed alternations in corticosterone levels, learning and memory, and the PPI of the ASR measures in APP NL-G-F/NL-G-F offspring of dams exposed to gestational noise stress. In-depth quantifications of the Aβ plaque accumulation were also performed at 6 months. The results indicated an age-dependent deterioration of sensorimotor gating, long-lasting PS-induced abnormalities in PPI magnitudes, as well as deficits in spatial memory. The PS also resulted in a higher Aβ aggregation predominantly in brain areas associated with the PPI modulation network. The findings suggest the contribution of a PS-induced hypothalamic-pituitary-adrenal (HPA) axis hyperactivity in regulating the PPI modulation substrates leading to the abnormal development of the neural protection system in response to disruptive stimuli. The long-lasting HPA axis dysregulation appears to be the major underlying mechanism in precipitating the Aβ deposition, especially in brain areas contributed to the PPI modulation network.

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          Author and article information

          Journal
          Cereb Cortex
          Cereb. Cortex
          cercor
          Cerebral Cortex (New York, NY)
          Oxford University Press
          1047-3211
          1460-2199
          January 2020
          09 May 2019
          10 January 2021
          : 30
          : 1
          : 311-325
          Affiliations
          [1 ] Department of Neuroscience , Canadian Centre for Behavioural Neuroscience, University of Lethbridge, Lethbridge, Alberta, Canada
          [2 ] Department of Basic Sciences in Rehabilitation , School of Rehabilitation Sciences, Iran University of Medical Science, Tehran, Iran
          Author notes
          Address correspondence to Bryan E. Kolb and Majid H. Mohajerani, Department of Neuroscience, Canadian Centre for Behavioural Neuroscience, University of Lethbridge, Lethbridge, Alberta, T1K 3M4, Canada. Email: kolb@ 123456uleth.ca and mohajerani@ 123456uleth.ca .
          Article
          PMC7029700 PMC7029700 7029700 bhz089
          10.1093/cercor/bhz089
          7029700
          31070710
          f15d5038-8699-4d0b-bf4b-baf2645e071c
          © The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

          This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model ( https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

          History
          Page count
          Pages: 15
          Funding
          Funded by: Canadian Institute for Advanced Research 10.13039/100007631
          Award ID: 33033
          Funded by: Alzheimer Society of Canada 10.13039/501100000143
          Award ID: 43674
          Funded by: Alberta Alzheimer Research Program
          Award ID: PAZ17010
          Award ID: PAZ15010
          Funded by: Alberta Innovates 10.13039/501100009192
          Award ID: 43568
          Funded by: Natural Sciences and Engineering Research Council of Canada 10.13039/501100000038
          Award ID: 40352
          Funded by: Canadian Institutes of Health Research 10.13039/501100000024
          Award ID: 390930
          Categories
          Original Article

          sensorimotor gating,prepulse inhibition,corticosterone,noise,Alzheimer's disease,Acoustic startle reflex,HPA axis,prenatal stress,amyloid-beta plaque

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