Social withdrawal and anxiety-like behavior have an impact on zebrafish adult neurogenesis

Panagiotis Perdikaris; Paulina Prouska; Catherine R Dermon

doi:10.3389/fnbeh.2023.1244075

Social withdrawal and anxiety-like behavior have an impact on zebrafish adult neurogenesis

Front Behav Neurosci. 2023 Oct 16:17:1244075. doi: 10.3389/fnbeh.2023.1244075. eCollection 2023.

Authors

Panagiotis Perdikaris¹, Paulina Prouska¹, Catherine R Dermon¹

Affiliation

¹ Laboratory of Human and Animal Physiology, Department of Biology, University of Patras, Patras, Greece.

Abstract

Introduction: Accumulating evidence highlights the key role of adult neurogenesis events in environmental challenges, cognitive functions and mood regulation. Abnormal hippocampal neurogenesis has been implicated in anxiety-like behaviors and social impairments, but the possible mechanisms remain elusive.

Methods: The present study questioned the contribution of altered excitation/inhibition as well as excessive neuroinflammation in regulating the neurogenic processes within the Social Decision-Making (SDM) network, using an adult zebrafish model displaying NMDA receptor hypofunction after sub-chronic MK-801 administration. For this, the alterations in cell proliferation and newborn cell densities were evaluated using quantitative 5-Bromo-2'-Deoxyuridine (BrdU) methodology.

Results: In short-term survival experiments. MK-801-treated zebrafish displayed decreased cell proliferation pattern within distinct neurogenic zones of telencephalic and preoptic SDM nodes, in parallel to the social withdrawal and anxiety-like comorbidity. BrdU+ cells co-expressed the pro-inflammatory marker IL-1β solely in MK-801-treated zebrafish, indicating a role of inflammation. Following the cessation of drug treatment, significant increases in the BrdU+ cell densities were accompanied by the normalization of the social and anxiety-like phenotype. Importantly, most labeled cells in neurogenic zones showed a radial glial phenotype while a population of newborn cells expressed the early neuronal marker TOAD or mGLuR5, the latter suggesting the possible involvement of metabotropic glutamate receptor 5 in neurogenic events.

Discussion: Overall, our results indicate the role of radial glial cell proliferation in the overlapping pathologies of anxiety and social disorders, observed in many neuropsychiatric disorders and possibly represent potential novel targets for amelioration of these symptoms.

Keywords: MK-801; NMDAR hypofunction; cell proliferation; mGLuR5; neurogenesis; social deficits; zebrafish.

Grants and funding

Part of the work was supported by the H.F.R.I (Hellenic Foundation for Research and Innovation) scholarship to Perdikaris Panagiotis and by the European Union and Greek National Funds through the Operational Program Competitiveness, Entrepreneurship and Innovation, under the call RESEARCH—CREATE—INNOVATE (project code: T1EDK-04290).