Methyl jasmonate rescues structural alterations in cortico-limbic neurons produced by the unpredictable chronic mild stress model of depression

Abstract

The unpredictable chronic mild stress (UCMS) mouse model of depression causes a variety of neuronal structural alterations ranging from dendritic spines loss and dendrite arbor retraction to spine proliferation in brain regions involved in the control of mood. Based on data showing that the plant stress hormone methyl jasmonate (MJ: methyl acetate-2,2-d2) mimics the effect of imipramine in rescuing the UCMS-induced depressive behavioral phenotype, here we examine whether the UCMS protocol used to demonstrate the antidepressant action of the compound triggers structural alterations in basolateral amygdala, hippocampus and prefrontal cortex which can be rescued by MJ treatment. Male C57BL/6 mice were injected with MJ (50 mg/kg) or saline (SAL) before each of the two daily exposures to UCMS administered over a 10-day period. Home cage, daily manipulated, SAL-injected mice served as controls (CTRL). On day 11, mice were sacrificed for Golgi-staining. Results show that in comparison with CTRL mice, SAL+UCMS mice exhibit a massive reduction in spine density and dendritic arbor extension/complexity in the three regions examined. Remarkably, MJ+UCMS mice show an alleviation of neuronal structural alterations in the three regions, with a more complete recovery observed in the prefrontal cortex. Our data provide further validation of the antidepressant action of the compound by revealing its efficacy in globally preventing the collapse in synaptic density and neuronal connectivity identified as key nodes of the mood circuitry.