Leukocyte Telomere Length in Major Depression: Correlations with Chronicity, Inflammation and Oxidative Stress - Preliminary Findings

Depression is associated with an unusually high rate of aging-related illnesses and early mortality. One aspect of “accelerated aging” in depression may be shortened leukocyte telomeres. When telomeres critically shorten, as often occurs with repeated mitoses or in response to oxidation and inflammation, cells may die. Indeed, leukocyte telomere shortening predicts early mortality and medical illnesses in non-depressed populations. We sought to determine if leukocyte telomeres are shortened in Major Depressive Disorder (MDD), whether this is a function of lifetime depression exposure and whether this is related to putative mediators, oxidation and inflammation.Leukocyte telomere length was compared between 18 unmedicated MDD subjects and 17 controls and was correlated with lifetime depression chronicity and peripheral markers of oxidation (F2-isoprostane/Vitamin C ratio) and inflammation (IL-6). Analyses were controlled for age and sex.The depressed group, as a whole, did not differ from the controls in telomere length. However, telomere length was significantly inversely correlated with lifetime depression exposure, even after controlling for age (p<0.05). Average telomere length in the depressed subjects who were above the median of lifetime depression exposure (≥9.2 years' cumulative duration) was 281 base pairs shorter than that in controls (p<0.05), corresponding to approximately seven years of “accelerated cell aging.” Telomere length was inversely correlated with oxidative stress in the depressed subjects (p<0.01) and in the controls (p<0.05) and with inflammation in the depressed subjects (p<0.05).These preliminary data indicate that accelerated aging at the level of leukocyte telomeres is proportional to lifetime exposure to MDD. This might be related to cumulative exposure to oxidative stress and inflammation in MDD. This suggest that telomere shortening does not antedate depression and is not an intrinsic feature. Rather, telomere shortening may progress in proportion to lifetime depression exposure

Stress-inducible-stem cells: a new view on endocrine, metabolic and mental disease?

Contains fulltext : 202946.pdf (publisher's version ) (Open Access

Regulatory role of the cannabinoid CB 2

BACKGROUND AND PURPOSE: Stress exposure produces excitotoxicity and neuroinflammation, contributing to the cellular damage observed in stress-related neuropathologies. The endocannabinoids provide a homeostatic system, present in stress-responsive neural circuits. Here, we have assessed the possible regulatory role of cannabinoid CB(2) receptors in stress-induced excitotoxicity and neuroinflammation. EXPERIMENTAL APPROACH: We used wild type (WT), transgenic overexpressing CB(2) receptors (CB2xP) and CB(2) receptor knockout (CB2-KO) mice exposed to immobilization and acoustic stress (2 h·day(−1) for 4 days). The CB(2) receptor agonist JWH-133 was administered daily (2 mg·kg(−1), i.p.) to WT and CB2-KO animals. Glutamate uptake was measured in synaptosomes from frontal cortex; Western blots and RT-PCR were used to measure proinflammatory cytokines, enzymes and mediators in homogenates of frontal cortex. KEY RESULTS: Increased plasma corticosterone induced by stress was not modified by manipulating CB(2) receptors. JWH-133 treatment or overexpression of CB(2) receptors increased control levels of glutamate uptake, which were reduced by stress back to control levels. JWH-133 prevented the stress-induced increase in proinflammatory cytokines (TNF-α and CCL2), in NF-κB, and in NOS-2 and COX-2 and in the consequent cellular oxidative and nitrosative damage (lipid peroxidation). CB2xP mice exhibited anti-inflammatory or neuroprotective actions similar to those in JWH-133 pretreated animals. Conversely, lack of CB(2) receptors (CB2-KO mice) exacerbated stress-induced neuroinflammatory responses and confirmed that effects of JWH-133 were mediated through CB(2) receptors. CONCLUSIONS AND IMPLICATIONS: Pharmacological manipulation of CB(2) receptors is a potential therapeutic strategy for the treatment of stress-related pathologies with a neuroinflammatory component, such as depression

Stress-inducible-stem cells:a new view on endocrine, metabolic and mental disease?

In general terms we all use the word“stress”to describe ourdiscomfort in coping with challenges of daily life. This ismostly related to our subjective perceptions of workloadand/or other unexpected physical or mental efforts we areexposed to. The term is derived from the concept of stress asa reaction to internal and external stimuli requiring acute orchronic adaptations, as introduced by Hans Selye in thesecond half of the last century [1–3].Published versio