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  Hippocampal insulin resistance links maternal obesity with impaired neuronal plasticity in adult offspring

Schmitz, L., Kuglin, R., Bae-Gartz, I., Janoschek, R., Appel, S., Mesaros, A., et al. (2017). Hippocampal insulin resistance links maternal obesity with impaired neuronal plasticity in adult offspring. Psychoneuroendocrinology, 89, 46-52. doi:10.1016/j.psyneuen.2017.12.023.

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Item Permalink: https://hdl.handle.net/21.11116/0000-0001-592C-B Version Permalink: https://hdl.handle.net/21.11116/0000-0001-592D-A
Genre: Journal Article

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https://www.ncbi.nlm.nih.gov/pubmed/29324300 (Any fulltext)
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 Creators:
Schmitz, L.1, Author
Kuglin, R.1, Author
Bae-Gartz, I.1, Author
Janoschek, R.1, Author
Appel, S.1, Author
Mesaros, A.1, Author
Jakovcevski, I.1, Author
Vohlen, C.1, Author
Handwerk, M.1, Author
Ensenauer, R.1, Author
Dotsch, J.1, Author
Hucklenbruch-Rother, E.1, Author
Affiliations:
1Max Planck Institute for Biology of Ageing, Max Planck Society, Joseph-Stelzmann-Str. 9b, D-50931 Cologne, DE, ou_1942284              

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Free keywords: Hippocampus Insulin resistance Maternal obesity Synapse
 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.

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 Dates: 2017
 Publication Status: Issued
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 Identifiers: Other: 29324300
DOI: 10.1016/j.psyneuen.2017.12.023
ISSN: 1873-3360 (Electronic)0306-4530 (Linking)
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Title: Psychoneuroendocrinology
Source Genre: Journal
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Pages: - Volume / Issue: 89 Sequence Number: - Start / End Page: 46 - 52 Identifier: -