Ricci, Serena (2017) PREP1 DEFICIENCY AFFECTS OLFACTORY SYSTEM INTEGRITY BY IMPAIRING TRKB-MEDIATED NEUROTROPHIC SIGNALLING. [Tesi di dottorato]

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Item Type: Tesi di dottorato
Lingua: English
Title: PREP1 DEFICIENCY AFFECTS OLFACTORY SYSTEM INTEGRITY BY IMPAIRING TRKB-MEDIATED NEUROTROPHIC SIGNALLING
Creators:
CreatorsEmail
Ricci, SerenaSERENA.RICCI@UNINA.IT
Date: 4 April 2017
Number of Pages: 65
Institution: Università degli Studi di Napoli Federico II
Department: Scienze Mediche Traslazionali
Scuola di dottorato: Medicina clinica e sperimentale
Dottorato: Medicina clinica e sperimentale
Ciclo di dottorato: 29
Coordinatore del Corso di dottorato:
nomeemail
Marone, Giannimarone@unina.it
Tutor:
nomeemail
Formisano, PietroUNSPECIFIED
Date: 4 April 2017
Number of Pages: 65
Uncontrolled Keywords: PREP1, OLFACTORY, BDNF
Settori scientifico-disciplinari del MIUR: Area 06 - Scienze mediche > MED/05 - Patologia clinica
Date Deposited: 28 Apr 2017 12:33
Last Modified: 13 Mar 2018 10:37
URI: http://www.fedoa.unina.it/id/eprint/11508
DOI: 10.6093/UNINA/FEDOA/11508

Abstract

Prep1 is a transcription factor belonging to the TALE proteins, which plays an important role in the embryonic development of the hindbrain. However, as reported on web-based atlas, morphological data revealed that Prep1 expression is kept also in adult mouse brain and, in particular, within the olfactory bulb (OB), even though its function is still unknown. In order to investigate the role of Prep1 in olfactory nuclei I used a prep1 hypomorphic mouse (prep1i/+), which express about 55-57% of protein. Brain morphological analysis revealed that prep1i/+ mice feature a significant reduction of OB area, a reduced number of periglomerular interneurons and an increased number of mitral cells within the main olfactory bulb, compared to WT mice. prep1i/+ mice OB cytochrome C oxidase staining showed also a reduced neuronal metabolism within the glomerular layer. Consistently, olfactory perception test highlighted that hypomorphic mice display a low ability to distinguish odor scents, accompanied to a significant locomotor hypoactivity. Molecular analysis, indeed, revealed that prep1i/+ mouse olfactory nuclei express reduced levels of TrkB, the downstream receptor of BDNF, the main neurotrophic factor involved in olfactory plasticity and functions. In parallel, also a decreased activation of molecular mediators involved in TrkB-mediated neurotrophic signalling (Akt, ERK) was observed. Congruously, mouse neuronal cells (N2A) overexpressing Prep1 showed increased cell growth, viability and metabolism, with high levels of TrkB expression and Akt/ERK phosphorylation, compared to control cells. Thus, our data suggest that Prep1 deficiency alters olfactory system morpho-functional integrity by affecting TrkB expression and signalling pathway, giving a rationale to further investigate Prep1 as potential marker in olfactory dysfunctions associated to impaired responsiveness to BDNF signalling.

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