Maternal Chronic Ultrasound Stress Provokes Immune Activation and Behavioral Deficits in the Offspring: A Mouse Model of Neurodevelopmental Pathology

Author:

Pavlov Dmitrii12ORCID,Gorlova Anna2,Haque Abrar1,Cavalcante Carlos3,Svirin Evgeniy2,Burova Alisa2ORCID,Grigorieva Elizaveta2,Sheveleva Elizaveta2,Malin Dmitry4,Efimochkina Sofia4,Proshin Andrey5ORCID,Umriukhin Aleksei4,Morozov Sergey2,Strekalova Tatyana2

Affiliation:

1. Hotchkiss Brain Institute, University of Calgary, Calgary, AB T2N 1N4, Canada

2. Laboratory of Cognitive Dysfunctions, Institute of General Pathology and Pathophysiology, Russian Academy of Medical Sciences, 125315 Moscow, Russia

3. Department of Human Health and Science, MacEwan University, Edmonton, AB T5J 4S2, Canada

4. Laboratory of Psychiatric Neurobiology, Department of Normal Physiology, Institute of Molecular Medicine, Sechenov First Moscow State Medical University, 119991 Moscow, Russia

5. P.K. Anokhin Research Institute of Normal Physiology, 125315 Moscow, Russia

Abstract

Neurodevelopmental disorders stemming from maternal immune activation can significantly affect a child’s life. A major limitation in pre-clinical studies is the scarcity of valid animal models that accurately mimic these challenges. Among the available models, administration of lipopolysaccharide (LPS) to pregnant females is a widely used paradigm. Previous studies have reported that a model of ‘emotional stress’, involving chronic exposure of rodents to ultrasonic frequencies, induces neuroinflammation, aberrant neuroplasticity, and behavioral deficits. In this study, we explored whether this model is a suitable paradigm for maternal stress and promotes neurodevelopmental abnormalities in the offspring of stressed females. Pregnant dams were exposed to ultrasound stress for 21 days. A separate group was injected with LPS on embryonic days E11.5 and E12.5 to mimic prenatal infection. The behavior of the dams and their female offspring was assessed using the sucrose test, open field test, and elevated plus maze. Additionally, the three-chamber sociability test and Barnes maze were used in the offspring groups. ELISA and qPCR were used to examine pro-inflammatory changes in the blood and hippocampus of adult females. Ultrasound-exposed adult females developed a depressive-like syndrome, hippocampal overexpression of GSK-3β, IL-1β, and IL-6 and increased serum concentrations of IL-1β, IL-6, IL-17, RANTES, and TNFα. The female offspring also displayed depressive-like behavior, as well as cognitive deficits. These abnormalities were comparable to the behavioral changes induced by LPS. The ultrasound stress model can be a promising animal paradigm of neurodevelopmental pathology associated with prenatal ‘emotional stress’.

Funder

Institute of General Pathology and Pathophysiology

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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