Isolation-rearing differentially affect behavioural phenotype and the hippocampal cytoskeletal microtubular proteins and synaptic markers in Sprague Dawley and Flinders Sensitive Line rats.

Abstract

The Flinders Sensitive Line (FSL) rats obtained by selective breeding of Sprague-Dawley (SD) are considered a genetic model of depressive disorders. Growing evidence suggests that neuronal alterations at cytoskeletal microtubules and synaptic structure may be involved in the pathogenesis of depression. This study compared the effects of a 39 day isolation-rearing period (IR-1 to IR-39) that started during the fourth post-natal week in male SD and FSL rats. Animals were exposed to the elevated plus-maze (EPM) on IR-35 or the open-field on IR-36 and sacrificed on IR-39. The hippocampus was dissected for the western-blot analyses of tyrosinated/detyrosinated a-tubulin ratio (Tyr/Glu-Tub; microtubule dynamics index), synaptophysin (pre-synaptic marker), PSD-95 (post-synaptic marker) and spinophilin (dendritic-spines marker). Isolation-rearing increased anxiety in the EPM in SD rats, but decreased it in FSL. Locomotor activity in the open-field was lower in FSL compared with SD independently from the housing conditions. Additionally, isolated SD showed increased hippocampal Tyr/Glu-Tub and decreased PSD-95 and spinophilin compared to group-housed SD. Isolation-rearing did not change PSD-95 in FSL rats, but decreased Tyr/Glu-Tub and increased spinophilin,. Synaptophysin was unchanged by isolation-rearing in both strains. Isolation-rearing induced opposite response to the EPM in SD and FSL rats. Such behavioural phenotype was paralleled by hippocampal changes in microtubular proteins and synaptic markers suggesting that isolation-rearing differentially affects cytoskeletal and dendritic structure in SD and FSL. Particularly, isolation-rearing appeared to increase microtubule dynamics and to induce major dendritic impairments in SD, while isolated FSL showed decreased microtubule dynamics accompanied by specific remodelling of the dendritic-spines.