Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/128512
Citations
Scopus Web of Science® Altmetric
?
?
Type: Journal article
Title: Hypervulnerability of the adolescent prefrontal cortex to nutritional stress via reelin deficiency
Author: Labouesse, M.
Lassalle, O.
Richetto, J.
Iafrati, J.
Weber-Stadlbauer, U.
Notter, T.
Gschwind, T.
Pujadas, L.
Soriano, E.
Reichelt, A.
Labouesse, C.
Langhans, W.
Chavis, P.
Meyer, U.
Citation: Molecular Psychiatry, 2017; 22(7):961-971
Publisher: Nature
Issue Date: 2017
ISSN: 1359-4184
1476-5578
Statement of
Responsibility: 
MA Labouesse, O Lassalle, J Richetto, J Iafrati, U Weber-Stadlbauer, T Notter ... et al.
Abstract: Overconsumption of high-fat diets (HFDs) can critically affect synaptic and cognitive functions within telencephalic structures such as the medial prefrontal cortex (mPFC). The underlying mechanisms, however, remain largely unknown. Here we show that adolescence is a sensitive period for the emergence of prefrontal cognitive deficits in response to HFD. We establish that the synaptic modulator reelin (RELN) is a critical mediator of this vulnerability because (1) periadolescent HFD (pHFD) selectively downregulates prefrontal RELN+ cells and (2) augmenting mPFC RELN levels using transgenesis or prefrontal pharmacology prevents the pHFD-induced prefrontal cognitive deficits. We further identify N-methyl-d-aspartate-dependent long-term depression (NMDA-LTD) at prefrontal excitatory synapses as a synaptic signature of this association because pHFD abolishes NMDA-LTD, a function that is restored by RELN overexpression. We believe this study provides the first mechanistic insight into the vulnerability of the adolescent mPFC towards nutritional stress, such as HFDs. Our findings have primary relevance to obese individuals who are at an increased risk of developing neurological cognitive comorbidities, and may extend to multiple neuropsychiatric and neurological disorders in which RELN deficiency is a common feature.
Keywords: Prefrontal Cortex
Rights: © 2017 Macmillan Publishers Limited, part of Springer Nature.
RMID: 1000025746
DOI: 10.1038/mp.2016.193
Grant ID: http://purl.org/au-research/grants/arc/DE140101071
Appears in Collections:Animal and Veterinary Sciences publications

Files in This Item:
There are no files associated with this item.


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.