Emotional behavior in aquatic organisms? Lessons from crayfish and zebrafish

Experimental animal models are a valuable tool to study the neurobiology of emotional behavior and mechanisms underlying human affective disorders. Mounting evidence suggests that various aquatic organisms, including both vertebrate (e.g., zebrafish) and invertebrate (e.g., crayfish) species, may be relevant to study animal emotional response and its deficits. Ideally, model organisms of disease should possess considerable genetic and physiological homology to mammals, display robust behavioral and physiological responses to stress, and should be sensitive to a wide range of drugs known to modulate stress and affective behaviors. Here, we summarize recent findings in the field of zebrafish- and crayfish-based tests of stress, anxiety, aggressiveness and social preference, and discuss further perspectives of using these novel model organisms in translational biological psychiatry. Outlining the remaining questions in this field, we also emphasize the need in further development and a wider use of crayfish and zebrafish models to study the pathogenesis of affective disorders. © 2019 Wiley Periodicals, Inc.MCS is currently supported by National Funds through FCT ‐ Foundation for Science and Technology. AVK is supported by the Russian Science Foundation grant 19‐15‐00053. KAD is supported by the Fellowship of the President of Russia and SPSU Rector Productivity Fellowship for PhD Students. CM is supported by CNPq/Brazil under Edital Universal 2016 (400726/2016‐5). PMA and FB are supported by the strategic plan of MARE ‐ Marine and Environmental Sciences Centre (UID/MAR/04292/2019)

Spatial Distribution of Neuropathology and Neuroinflammation Elucidate the Biomechanics of Fluid Percussion Injury

Diffuse brain injury is better described as multi-focal, where pathology can be found adjacent to seemingly uninjured neural tissue. In experimental diffuse brain injury, pathology and pathophysiology have been reported far more lateral than predicted by the impact site. We hypothesized that local thickening of the rodent skull at the temporal ridges serves to focus the intracranial mechanical forces experienced during brain injury and generate predictable pathology. We demonstrated local thickening of the skull at the temporal ridges using contour analysis on magnetic resonance imaging. After diffuse brain injury induced by midline fluid percussion injury (mFPI), pathological foci along the anterior-posterior length of cortex under the temporal ridges were evident acutely (1, 2, and 7 days) and chronically (28 days) post-injury by deposition of argyophilic reaction product. Area CA3 of the hippocampus and lateral nuclei of the thalamus showed pathological change, suggesting that mechanical forces to or from the temporal ridges shear subcortical regions. A proposed model of mFPI biomechanics suggests that injury force vectors reflect off the skull base and radiate toward the temporal ridge, thereby injuring ventral thalamus, dorsolateral hippocampus, and sensorimotor cortex. Surgically thinning the temporal ridge before injury reduced injury-induced inflammation in the sensorimotor cortex. These data build evidence for temporal ridges of the rodent skull to contribute to the observed pathology, whether by focusing extracranial forces to enter the cranium or intracranial forces to escape the cranium. Pre-clinical investigations can take advantage of the predicted pathology to explore injury mechanisms and treatment efficacy

Complex behavioral alterations after diffuse traumatic axonal injury in mice are normalized by post-injury neutralization of interleukin-1β

Abstract Wide-spread traumatic axonal injury (TAI), clinically known as diffuse axonal injury, results in brain network dysfunction which commonly leads to persisting cognitive and behavioral impairments following traumatic brain injury (TBI). TBI induces a complex neuroinflammatory response, frequently located at sites of axonal pathology. The role of the pro-inflammatory cytokine interleukin-1β (IL-1β) in TAI has not been established. An IL-1β-neutralizing or a control antibody was administered intraperitoneally at 30 min following central fluid percussion injury (cFPI) in mice, a model of wide-spread TAI. Animals subjected to moderate cFPI (n=41) were compared to sham-injured controls (n=20) and untreated, naive animals (n=9). The anti-IL-1β antibody reached the target brain regions in adequate therapeutic concentrations (up to ~30µg /g brain tissue) at 24h post-injury in both cFPI-injured (n=5) and sham-injured animals (n=3) whereas at 72 h post-injury (n=3 cFPI-injured), the antibody concentration was lower (up to ~18µg /g brain tissue). Functional outcome was analyzed using the multivariate concentric square field™ (MCSF) test at 2 and 9 days post-injury and the Morris water maze (MWM) at 14-21 days post-injury. Following TAI, the IL-1β-neutralizing antibody resulted in an improved behavioral outcome, including normalized behavioral profiles in the MCSF test, and improved performance in the MWM probe (memory) trial, although without influencing MWM learning. The IL1β neutralizing treatment did not influence cerebral ventricle size or the number of activated microglia at 21 days post- injury. These findings support the hypothesis that IL-1β is an important contributor to the processes causing complex cognitive and behavioral disturbances following TAI. Keywords: Interleukin 1β, central fluid percussion injury, mice, multivariate concentric square field test, Morris water maze, microglia, traumatic brain injury, traumatic axonal injury, diffuse axonal injury, behavioral outcom