The stress impact on synaptic function and brain architecture: a key to mood and anxiety disorders

Stressful events represent main risk factors in the etiopathogen- esis of neuropsychiatric disorders. The stress response implies metabolic and plasticity changes, aimed to promote adaptation [1]. However, when the stressor is chronic, uncontrollable, or over- whelming, the response could be inadequate or overused, in turn leading to impaired function and increased risk to develop stress- related pathologies. Stress has been shown to deeply affect structural and func- tional plasticity, particularly within the prefrontal cortex (PFC), a brain area with critical roles in cognitive function [2]. We have shown that acute footshock (FS)-stress rapidly enhances excitatory (glutamatergic) transmission in PFC, together with an increase in the number of docked vesicles and of small excitatory synapses, and that chronic antidepressants attenuate these effects [3,4]. We have also shown that the increase of trafficking into the readily releasable pool of glutamate vesicles induced by acute stress in PFC is dependent on synaptic, non-genomic action of glucocorticoids [5]. We are now showing that acute FS-stress has biphasic effects on synaptic function and neuronal architecture in PFC. Indeed, FS- stress has early and rapid enhancing morphological, functional and behavioral effects followed, in the days and weeks after, by opposite changes. We are also studying chronic mild stress, which induces different modifications of structural-functional plasticity and cognitive behavior. Chronic antidepressants limit detrimental effects of both acute and chronic stress. A better knowledge of the molecular effectors involved in the effects of chronic and acute stress may be useful to understand the pathophysiology of stress-related disorders, and to identify new therapeutic targets.