Universität zu Köln

Schmitz, Lisa, Kuglin, Rebecca, Bae-Gartz, Inga, Janoschek, Ruth, Appel, Sarah, Mesaros, Andrea, Jakovcevski, Igor, Vohlen, Christina, Handwerk, Marion, Ensenauer, Regina, Doetsch, Jorg and Hucklenbruch-Rother, Eva (2018). Hippocampal insulin resistance links maternal obesity with impaired neuronal plasticity in adult offspring. Psychoneuroendocrinology, 89. S. 46 - 53. OXFORD: PERGAMON-ELSEVIER SCIENCE LTD. ISSN 0306-4530

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Abstract

Objective: Maternal obesity and a disturbed metabolic environment during pregnancy and lactation have been shown to result in many long-term health consequences for the offspring. Among them, impairments in neurocognitive development and performance belong to the most dreaded ones. So far, very few mechanistic approaches have aimed to determine the responsible molecular events. Methods: In a mouse model of maternal diet-induced obesity and perinatal hyperinsulinemia, we assessed adult offspring's hippocampal insulin signaling as well as concurrent effects on markers of hippocampal neurogenesis, synaptic plasticity and function using western blotting and immunohistochemistry. In search for a potential link between neuronal insulin resistance and hippocampal plasticity, we additionally quantified protein expression of key molecules of synaptic plasticity in an in vitro model of acute neuronal insulin resistance. Results: Maternal obesity and perinatal hyperinsulinemia result in adult hippocampal insulin resistance with subsequently reduced hippocampal mTor signaling and altered expression of markers of neurogenesis (doublecortin), synaptic plasticity (FoxO1, pSynapsin) and function (vGlut, vGAT) in the offspring. The observed effects are independent of the offspring's adult metabolic phenotype and can be associated with multiple previously reported behavioral abnormalities. Additionally, we demonstrate that induction of insulin resistance in cultured hippocampal neurons reduces mTor signaling, doublecortin and vGAT protein expression. Conclusions: Hippocampal insulin resistance might play a key role in mediating the long-term effects of maternal obesity and perinatal hyperinsulinemia on hippocampal plasticity and the offspring's neurocognitive outcome.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Schmitz, Lisa UNSPECIFIED UNSPECIFIED UNSPECIFIED Kuglin, Rebecca UNSPECIFIED UNSPECIFIED UNSPECIFIED Bae-Gartz, Inga UNSPECIFIED UNSPECIFIED UNSPECIFIED Janoschek, Ruth UNSPECIFIED UNSPECIFIED UNSPECIFIED Appel, Sarah UNSPECIFIED UNSPECIFIED UNSPECIFIED Mesaros, Andrea UNSPECIFIED UNSPECIFIED UNSPECIFIED Jakovcevski, Igor UNSPECIFIED UNSPECIFIED UNSPECIFIED Vohlen, Christina UNSPECIFIED UNSPECIFIED UNSPECIFIED Handwerk, Marion UNSPECIFIED UNSPECIFIED UNSPECIFIED Ensenauer, Regina UNSPECIFIED UNSPECIFIED UNSPECIFIED Doetsch, Jorg UNSPECIFIED UNSPECIFIED UNSPECIFIED Hucklenbruch-Rother, Eva UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-194014
DOI:	10.1016/j.psyneuen.2017.12.023
Journal or Publication Title:	Psychoneuroendocrinology
Volume:	89
Page Range:	S. 46 - 53
Date:	2018
Publisher:	PERGAMON-ELSEVIER SCIENCE LTD
Place of Publication:	OXFORD
ISSN:	0306-4530
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language HIGH-FAT DIET; INFLAMMATION; PERFORMANCE; EXPOSURE; BEHAVIOR Multiple languages Endocrinology & Metabolism; Neurosciences; Psychiatry Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/19401