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Astrocyte pathology in the prefrontal cortex impairs the cognitive function of rats

Molecular Psychiatry volume 19, pages 834–841 (2014)Cite this article

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Abstract

Interest in astroglial cells is rising due to recent findings supporting dynamic neuron–astrocyte interactions. There is increasing evidence of astrocytic dysfunction in several brain disorders such as depression, schizophrenia or bipolar disorder; importantly these pathologies are characterized by the involvement of the prefrontal cortex and by significant cognitive impairments. Here, to model astrocyte pathology, we injected animals with the astrocyte specific toxin L-α-aminoadipate (L-AA) in the medial prefrontal cortex (mPFC); a behavioral and structural characterization two and six days after the injection was performed. Behavioral data shows that the astrocyte pathology in the mPFC affects the attentional set-shifting, the working memory and the reversal learning functions. Histological analysis of brain sections of the L-AA-injected animals revealed a pronounced loss of astrocytes in the targeted region. Interestingly, analysis of neurons in the lesion sites showed a progressive neuronal loss that was accompanied with dendritic atrophy in the surviving neurons. These results suggest that the L-AA-induced astrocytic loss in the mPFC triggers subsequent neuronal damage leading to cognitive impairment in tasks depending on the integrity of this brain region. These findings are of relevance to better understand the pathophysiological mechanisms underlying disorders that involve astrocytic loss/dysfunction in the PFC.

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Acknowledgements

This work was supported by the Marie Curie Fellowship FP7-PEOPLE-2010-IEF 273936, BIAL Foundation Grants 138/2008 and 61/2010, FEDER funds through Operational program for competitiveness factors—COMPETE –, ON2 Programa Operacional Regional do Norte (ON.2—O Novo Norte), QREN/FEDER, and by national funds through FCT—Foundation for Science and Technology—project (PTDC/SAU-NSC/118194/2010) and fellowships (SFRH/BPD/66151/2009 and SFRH/BD/89714/2012).

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  1. Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal

    A Lima, V M Sardinha, A F Oliveira, M Reis, C Mota, M A Silva, F Marques, J J Cerqueira, L Pinto, N Sousa & J F Oliveira

  2. ICVS/3B’s—PT Government Associate Laboratory, Braga/Guimarães, Portugal

    A Lima, V M Sardinha, A F Oliveira, M Reis, C Mota, M A Silva, F Marques, J J Cerqueira, L Pinto, N Sousa & J F Oliveira

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Lima, A., Sardinha, V., Oliveira, A. et al. Astrocyte pathology in the prefrontal cortex impairs the cognitive function of rats. Mol Psychiatry 19, 834–841 (2014). https://doi.org/10.1038/mp.2013.182

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