Elsevier

Psychoneuroendocrinology

Volume 34, Supplement 1, December 2009, Pages S208-S216
Psychoneuroendocrinology

REVIEW
Neuronal plasticity: A link between stress and mood disorders

https://doi.org/10.1016/j.psyneuen.2009.05.014Get rights and content

Summary

Although stress represents the major environmental element of susceptibility for mood disorders, the relationship between stress and disease remains to be fully established. In the present article we review the evidence in support for a role of neuronal plasticity, and in particular of neurotrophic factors. Even though decreased levels of norepinephrine and serotonin may underlie depressive symptoms, compelling evidence now suggests that mood disorders are characterized by reduced neuronal plasticity, which can be brought about by exposure to stress at different stages of life. Indeed the expression of neurotrophic molecules, such as the neurotrophin BDNF, is reduced in depressed subjects as well as in experimental animals exposed to adverse experience at early stages of life or at adulthood. These changes show an anatomical specificity and might be sustained by epigenetic mechanisms.

Pharmacological intervention may normalize such defects and improve neuronal function through the modulation of the same factors that are defective in depression. Several studies have demonstrated that chronic, but not acute, antidepressant treatment increases the expression of BDNF and may enhance its localization at synaptic level. Antidepressant treatment can normalize deficits in neurotrophin expression produced by chronic stress paradigms, but may also alter the modulation of BDNF under acute stressful conditions. In summary, there is good agreement in considering neuronal plasticity, and the expression of key proteins such as the neurotrophin BDNF, as a central player for the effects of stress on brain function and its implication for psychopathology. Accordingly, effective treatments should not limit their effects to the control of neurotransmitter and hormonal dysfunctions, but should be able to normalize defective mechanisms that sustain the impairment of neuronal plasticity.

Section snippets

Neuronal plasticity and psychiatric illness

Neuronal plasticity refers to the ability of the nervous system to respond and adapt to environmental challenges and encompasses a series of functional and structural mechanisms that may lead to neuronal remodelling, formation of novel synapses and birth of new neurons. However, in a broader sense, neuronal plasticity is intimately linked to cellular responsiveness and may therefore be considered an index of the neuronal capability to adapt its function to a different demand. Failure of such

Stress and susceptibility to mood disorders

Stress represents the major precipitating factor in mood disorders. It may be inferred that affected subjects have a different threshold for stress susceptibility, which means that mechanisms that are required to cope with stress can be altered or less functional. The effects of stress on brain function depend on the timing and duration of the adverse experience. As already mentioned, adverse events early in life can be particularly relevant for later psychopathology since they will impact on

Neurotrophic factors as markers of plasticity

Network construction and reorganization, which are the main processes involved in neuroplasticity, are regulated by the level and pattern of synaptic activity generated in the nervous system. The discovery that excitatory neurotransmitters can stimulate new gene transcription by triggering an influx of calcium into postsynaptic suggested a mechanism by which stimulus-evoked neuronal activity might lead long-lasting changes in the structure and function of the nervous system. Specifically,

BDNF: a neurotrophin with multiple sites of regulation

BDNF is a member of the neurotrophin family that has an important role in development as well as in adult neuronal plasticity. A number of studies carried out in the last few years have demonstrated that BDNF has a sophisticated organization in terms of transcriptional, translational and posttranslational regulatory mechanisms.

With regard to BDNF transcription, its gene consists of nine 5′ untranslated exons (some of which are enriched in the CNS), each linked to individual promoter regions,

Neurotrophic factors in depression

Several papers have demonstrated, with different approaches, the relationship between neurotrophic factors and depression.

First of all, postmortem studies suggest that the expression of selected neurotrophic molecules is altered in the brain of depressed patients. Accordingly Evans and co-workers have shown a decreased expression of several genes associated with the fibroblast growth factor family (Evans et al., 2004). In particular the expression of FGF-1, FGF-2, and their receptors FGFR2 and

Modulation of BDNF expression by stress

A modulation of BDNF by stress was originally shown several years ago (Smith et al., 1995). Since than, evidence has been produced demonstrating the complex outcome of stress on the BDNF system. Because epidemiological studies have shown that stressful episodes in early life can increase the risk to develop depression (Heim et al., 2004), several authors have investigated the expression of BDNF in animal models that reproduce exposure to adverse life events.

These paradigms are based on the

Modulation of BDNF by antidepressant treatment

Since depression is characterized by a reduction of neuronal plasticity, which can be produced as a consequence of exposure to stress at different stages of life, it may be inferred that effective pharmacological treatments should be able to correct or normalize such deficits in order to achieve functional recovery. Indeed, speaking of depression, a key question has always been why therapeutic responses with antidepressants could only be achieved after at least 2–3 weeks of treatment, whereas

Antidepressant treatment modulate stress-induced changes of BDNF

Since stress is a major causative factor in depression, it is expected that antidepressant drugs could modulate stress responsiveness and susceptibility, which is altered in affected individuals.

First of all antidepressants can regulate the HPA axis, whose function is altered in stress and mood disorders. Indeed, it has been found that different stressors decrease glucocorticoid receptor (GR) levels in the hippocampus (Chen et al., 2008, Meyer et al., 2001), while antidepressant treatment can

Concluding remarks

In summary, the data herein reviewed suggest a close link between stress, neuronal plasticity and major depression. We believe that a putative mechanism through which stress can alter the susceptibility to mood disorders is the modulation of neuroplastic molecules, such as neurotrophins. Accordingly, antidepressant drugs are able to normalize defective mechanisms that sustain the impairment of neuronal plasticity and can increase neuronal resilience (Fig. 1). The understanding of these adaptive

Conflict of interest

None.

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