Event Abstract

Back to Event

Does BDNF loss of function in the prefrontal cortex underlie cognitive deficits in the subchronic phencyclidine model of schizophrenia?

Sara R. Tanqueiro1, 2*, Francisco M. Mouro1, 2, Ana M. Sebastião1, 2, Frederico S. Do Couto1, 2, 3, Neil Dawson4 and Maria J. Diógenes1, 2
  • 1 Institute of Pharmacology and Neurosciences, Faculty of Medicine, University of Lisbon, Portugal
  • 2 Institute of Molecular Medicine, Faculty of Medicine, University of Lisbon, Portugal
  • 3 Serviço de Psiquiatria e Saúde Mental, Centro Hospitalar Lisboa Norte, Portugal
  • 4 Faculty of Health and Medicine, Lancaster University, United Kingdom

Patients with schizophrenia, despite positive and negative symptoms, suffer from untreated cognitive deficits that have an enormous impact on their daily lives [1]. Alterations in BDNF levels, which has a crucial role in synaptic function and plasticity through the activation of TrkB-full length (FL) receptor [2-4], may have a role in the molecular mechanisms underlying cognitive dysfunction in schizophrenia [5]. Thus, this work aimed to characterize BDNF signalling in the subchronic phencyclidine (PCP) mouse model of schizophrenia. After subchronic treatment with PCP·HCl (10 mg/kg, i.p.) or vehicle, male C57BL/6 mice (10-week-old) were subjected to behavioural tests to confirm cognitive dysfunction. After behaviour, animals were sacrificed and samples from different brain areas were collected for molecular analysis. We observed impaired recognition memory (p<0.001, n=6-7, student's t-test) and decreased spontaneous alternation behaviour (p<0.5, n=5-7, student’s t-test) in PCP-treated mice suggesting dysfunction in the prefrontal cortex (PFC) and hippocampus (HIP). Both regions have long been known to play a central role in cognitive functions and their dysfunction has been implicated in schizophrenia. Importantly, BDNF signalling is not affected in the HIP of PCP-treated mice. BDNF was able to maintain its action upon LTP magnitude (p<0.05, n=7-12) and no differences were found at a molecular level in its protein levels (p>0.05, n=9-10) or TrkB-FL receptors (p>0.05, n=12). However, we found decreased protein levels of TrkB-FL (p<0.01, n=12, student’s t-test) in the PFC of PCP-treated mice. Thus, we are now evaluating BDNF function upon synaptic plasticity, for the first time in this brain area, in physiological conditions and PCP-treated animals. Overall, data has been encouraging us to continue scrutinizing BDNF signalling to evaluate whether its modulation could be part of a promising strategy in schizophrenia treatment.

References

[1] Fett AK, Viechtbauer W, Dominguez MD, Penn DL, van Os J, Krabbendam L. The relationship between neurocognition and social cognition with functional outcomes in schizophrenia: a meta-analysis. Neurosci Biobehav Rev 2011;35:573-588. [2] Lowenstein DH, Arsenault L. The effects of growth factors on the survival and differentiation of cultured dentate gyrus neurons. J Neurosci. 1996; 16:1759–1769 [3] Arevalo JC, Wu SH. Neurotrophin signaling: many exciting surprises! Cellular and Molecular Life Sciences. 2006; 63:1523–1537. [4] Reichardt LF. Neurotrophin-regulated signalling pathways. Philos Trans R Soc Lond B Biol Sci. 2006, 361(1473):1545–1564. [5] Nieto R, Kukuljan M, Silva H. BDNF and Schizophrenia: From Neurodevelopment to Neuronal Plasticity, Learning, and Memory. Front Psychiatry. 2013; 4: 45.

Keywords: Schizophrenia, Phencyclidine (PCP), Prefrontal Cortex, Hippocampus, BDNF (brain derived neurotrophic factor)

Conference: XVI Meeting of the Portuguese Society for Neuroscience (SPN2019), Lisboa, Portugal, 30 May - 1 Jun, 2019.

Presentation Type: Poster presentation

Topic: Psychiatric Disorders / Addiction

Citation: Tanqueiro SR, Mouro FM, Sebastião AM, Do Couto FS, Dawson N and Diógenes MJ (2019). Does BDNF loss of function in the prefrontal cortex underlie cognitive deficits in the subchronic phencyclidine model of schizophrenia?. Front. Cell. Neurosci. Conference Abstract: XVI Meeting of the Portuguese Society for Neuroscience (SPN2019). doi: 10.3389/conf.fncel.2019.01.00017

Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters.

The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated.

Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed.

For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions.

Received: 16 Apr 2019; Published Online: 27 Sep 2019.

* Correspondence: Ms. Sara R Tanqueiro, Institute of Pharmacology and Neurosciences, Faculty of Medicine, University of Lisbon, Lisbon, 1649-028, Portugal, saratanqueiro@medicina.ulisboa.pt