Acute stress-induced impairment of spatial memory is associated with decreased expression of neural cell adhesion molecule in the hippocampus and prefrontal cortex.
ABSTRACT There is an extensive literature describing how stress disturbs cognitive processing and can exacerbate psychiatric disorders. There is, however, an insufficient understanding of the molecular mechanisms involved in stress effects on brain and behavior.
Rats were given spatial memory training in a hippocampus-dependent water maze task. We investigated how a fear-provoking experience (predator exposure) would affect their spatial memory and neural cell adhesion molecule (NCAM) levels in the hippocampus, prefrontal cortex (PFC), amygdala, and cerebellum.
Whereas the control (nonstress) group exhibited excellent memory for the hidden platform location in the water maze, the cat-exposed (stress) group exhibited a profound impairment of memory and a marked suppression of levels of the NCAM-180 isoform in the hippocampus. Predator stress produced a more global reduction of NCAM levels in the PFC but had no effect on NCAM levels in the amygdala and cerebellum.
This work provides a novel perspective into dynamic and structure-specific changes in the molecular events involved in learning, memory, and stress. The selective suppression of NCAM-180 in the hippocampus and the more general suppression of NCAM in the PFC provide insight into the mechanisms underlying the great sensitivity of these two structures to be disturbed by stress.
Article: Chronic stress-induced cellular changes in the medial prefrontal cortex and their potential clinical implications: does hemisphere location matter?[show abstract] [hide abstract]
ABSTRACT: The prefrontal cortex (PFC) is implicated in a number of higher cognitive functions as well as processing emotions and regulation of stress responses. Hemispheric specialization of the PFC in humans in emotional processing is well documented, and there is evidence that a similar functional lateralization is present in all mammals. Recent findings suggest the possibility of an intrinsic structural hemispheric asymmetry in the rat medial PFC (mPFC). Specifically, interhemispheric differences have been found in the architecture of pyramidal cell apical dendritic trees together with hemispheric asymmetry in cell proliferation including gliogenesis. It is now well established that chronic stress has a profound impact on neural plasticity in a number of corticolimbic structures and affects the etiology, pathophysiology, and therapeutic outcome of most psychiatric disorders. We summarize recent experimental data documenting pronounced dendritic remodeling of pyramidal cells and suppressed gliogenesis in the mPFC of rats subjected to chronic stress or to artificially elevated glucocorticoid levels. The stress affect on these structural elements seems to be hemispheric specific, often abolishing or even reversing natural asymmetries seen at the cellular level. We discuss these preclinical observations with respect to clinical findings that show impaired function, altered lateralization and histopathological changes in the PFC in psychiatric patients. We argue that it is important to define the kinds of structural changes that result from long-term stress exposure because this knowledge will improve the identification of cellular endophenotypes in various psychiatric disorders.Behavioural Brain Research 07/2008; 190(1):1-13. · 3.42 Impact Factor
Article: Beneficial Effects of Tianeptine on Hippocampus-Dependent Long-Term Memory and Stress-Induced Alterations of Brain Structure and Function[show abstract] [hide abstract]
ABSTRACT: Tianeptine is a well-described antidepressant which has been shown to prevent stress from producing deleterious effects on brain structure and function. Preclinical studies have shown that tianeptine blocks stress-induced alterations of neuronal morphology and synaptic plasticity. Moreover, tianeptine prevents stress from impairing learning and memory, and, importantly, demonstrates memory-enhancing properties in the absence of stress. Recent research has indicated that tianeptine works by normalizing glutamatergic neurotransmission, a mechanism of action that may underlie its effectiveness as an antidepressant. These findings emphasize the value in focusing on the mechanisms of action of tianeptine, and specifically, the glutamatergic system, in the development of novel pharmacotherapeutic strategies in the treatment of depression.Pharmaceuticals. 01/2010;