Neuronal cytoskeletal alterations in an experimental model of depression.

ABSTRACT

It has been proposed that depression is associated with hippocampal morphological changes. The apical dendrite atrophy of hippocampal CA3 pyramidal neurons has been described in experimental models of depression. The aim of the present study was to determine which cytoskeletal components are involved in the morphological changes previously described in the hippocampus of depressed animals. The expression of different neuronal cytoskeletal markers was analyzed by immunohistochemistry in rats exposed to a learned helplessness paradigm, an experimental model of depression. Rats were trained with 60 inescapable foot shocks (0.6 mA/15 s) and escape latencies and failures were tested 4 days after training. Animals in which learned helplessness behavior persisted for 21 days were included in the depressed group. No foot shocks were delivered to control rats. Microtubule-associated protein 2 (MAP-2) and light (NFL; 68 kDa), medium (NFM; 160 kDa) and heavy (NFH; 200 kDa) neurofilament subunit immunostainings were analyzed employing morphometric parameters. In the depressed group, NFL immunostaining decreased 55% (P<0.05) and 60% (P<0.001) in CA3 and dentate gyrus, respectively. In the same areas, MAP-2, NFM and NFH immunostainings did not differ between depressed and control animals. Since NFL is present in the core of mature neurofilament, it is proposed that hippocampal depression-associated plastic alterations may be due to changes in the dynamics of the neurofilament assembly.