Structural plasticity and tianeptine:
cellular and molecular targets

by
McEwen BS, Magarinos AM, Reagan LP.
Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology,
The Rockefeller University,
New York, NY 10021, USA.
mcewen@rockvax.rockefeller.edu
Eur Psychiatry. 2002 Jul;17 Suppl 3:318-30.


ABSTRACT

The hippocampal formation, a structure involved in declarative, spatial and contextual memory, undergoes atrophy in depressive illness along with impairment in cognitive function. Animal model studies have shown that the hippocampus is a particularly sensitive and vulnerable brain region that responds to stress and stress hormones. Studies on models of stress and glucocorticoid actions reveal that the hippocampus shows a considerable degree of structural plasticity in the adult brain. Stress suppresses neurogenesis of dentate gyrus granule neurons, and repeated stress causes remodeling of dendrites in the CA3 region, a region that is particularly important in memory processing. Both forms of structural remodeling of the hippocampus are mediated by adrenal steroids working in concert with excitatory amino acids (EAA) and N-methyl-D-aspartate (NMDA) receptors. EAA and NMDA receptors are also involved in neuronal death that is caused in pyramidal neurons by seizures, head trauma, and ischemia, and alterations of calcium homeostasis that accompany age-related cognitive impairment. Tianeptine (tianeptine) is an effective antidepressant that prevents and even reverses the actions of stress and glucocorticoids on dendritic remodeling in an animal model of chronic stress. Multiple neurotransmitter systems contribute to dendritic remodeling, including EAA, serotonin, and gamma-aminobutyric acid (GABA), working synergistically with glucocorticoids. This review summarizes findings on neurochemical targets of adrenal steroid actions that may explain their role in the remodeling process. In studying these actions, we hope to better understand the molecular and cellular targets of action of tianeptine in relation to its role in influencing structural plasticity of the hippocampus.
PTSD
Neuroplasticity
Asthma prevention
Anxious depression
Tianeptine (Stablon)
Tianeptine: structure
Dopamine and neuroplasticity
Tianeptine and Panic Disorder
Ethanol withdrawal and tianeptine
Discriminative stimulus properties
Tree-shews, cortisol and the hippocampus
Neurobiology of mood, anxiety and emotion
Stress-induced hippocampal atrophy and dysfunction


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