Research Perspectives: Neuroscience:

Acute stress enhances the expression of neuroprotection- and neurogenesis-associated genes in the hippocampus of a mouse restraint model

Giuseppina Sannino, Lorenza Pasqualini, Eugenia Ricciardelli, Patricia Montilla, Laura Soverchia, Barbara Ruggeri, Silvia Falcinelli, Alessandra Renzi, Colleen Ludka, Thomas Kirchner, Thomas G. P. Grünewald, Roberto Ciccocioppo, Massimo Ubaldi and Gary Hardiman _

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Oncotarget. 2016; 7:8455-8465. https://doi.org/10.18632/oncotarget.7225

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Giuseppina Sannino1,2,3,*, Lorenza Pasqualini1,2,4,*, Eugenia Ricciardelli1,2, Patricia Montilla1,5, Laura Soverchia6, Barbara Ruggeri7, Silvia Falcinelli1,2, Alessandra Renzi1,2, Colleen Ludka1, Thomas Kirchner8, Thomas G. P. Grünewald3, Roberto Ciccocioppo6, Massimo Ubaldi6 and Gary Hardiman1,9

1 Department of Medicine, School of Medicine, University of California, La Jolla, California, USA

2 Facoltà di Scienze, Università Politecnica delle Marche, Ancona, Italy

3 Laboratory for Pediatric Sarcoma Biology, Institute of Pathology of the LMU Munich, Munich, Germany

4 Department of Urology, Medical University of Innsbruck, Innsbruck, Austria

5 Centre de Recherches en Cancérologie de Toulouse – CRCT, Toulouse, France

6 School of Pharmacy, Pharmacology Unit, University of Camerino, Camerino, Italy

7 Medical Research Council – Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King’s College London, London, United Kingdom

8 Institute of Pathology of the LMU Munich, Munich, Germany

9 Departments of Medicine, Public Health and Center for Genomics Medicine, Medical University of South Carolina, Charleston, South Carolina, USA

* These authors are joint first authors

Correspondence to:

Gary Hardiman, email:

Keywords: acute, restraint stress, hippocampus, neurogenesis, neuroprotection

Received: December 19, 2015 Accepted: January 26, 2016 Published: February 06, 2016


Stress arises from an external demand placed on an organism that triggers physiological, cognitive and behavioural responses in order to cope with that request. It is thus an adaptive response useful for the survival of an organism. The objective of this study was to identify and characterize global changes in gene expression in the hippocampus in response to acute stress stimuli, by employing a mouse model of short-term restraint stress. In our experimental design mice were subjected to a one time exposure of restraint stress and the regulation of gene expression in the hippocampus was examined 3, 12 and 24 hours thereafter. Microarray analysis revealed that mice which had undergone acute restraint stress differed from non-stressed controls in global hippocampal transcriptional responses. An up-regulation of transcripts contributing directly or indirectly to neurogenesis and neuronal protection including, Ttr, Rab6, Gh, Prl, Ndufb9 and Ndufa6, was observed. Systems level analyses revealed a significant enrichment for neurogenesis, neuron morphogenesis- and cognitive functions-related biological process terms and pathways. This work further supports the hypothesis that acute stress mediates a positive action on the hippocampus favouring the formation and the preservation of neurons, which will be discussed in the context of current data from the literature.

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