Behavioral, Genomic and Neurochemical Deficits Evoked by Neurotrauma in Adult Zebrafish (<i>Danio rerio</i>)

Abstract

Traumatic brain injury (TBI) is a serious biomedical problem with high prevalence and mortality risks. Understanding TBI in traditional (e.g., rodent) animal models often presents challenges due to the complexity of their brain and its limited regenerative capabilities. Here, we present novel data obtained using the zebrafish TBI model based on a stab wound of telencephalon, aiming to investigate behavioral and molecular consequences of TBI in zebrafish. Four days following the injury, adult zebrafish displayed hypolocomotion in the novel seen tank test and impaired working memory in the Y-maze test, paralleling behavioral deficits in rodent models and human TBI patients. Molecular analyses of key genes involved in the inflammatory response and cell death pathways revealed a remarkable upregulation of the interferon-stimulated gene 15 (isg15) in the injured telencephalon, a general biomarker for neuronal damage. Furthermore, noradrenaline (but not dopamine or serotonin) levels in whole-brain tissue declined following TBI, likely contributing to the observed cognitive deficits and implicating neurotransmitter dysregulation in TBI pathogenesis.