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Environmental enrichment (EE) that combines voluntary physical exercise, sensory and social stimuli, causes profound changes in rodent brain at molecular, anatomical and behavioral levels. Here, we show that EE efficiently reduces anxiety and depression-like behaviors in a mouse model of depression induced by long-term administration of corticosterone. Mechanisms underlying EE-related beneficial effects remain largely unexplored; however, our results point toward adiponectin, an adipocyte-secreted protein, as a main contributor. Indeed, adiponectin-deficient (adipo(-/-)) mice did not benefit from all the EE-induced anxiolytic and antidepressant-like effects as evidenced by their differential responses in a series of behavioral tests. Conversely, a single intravenous injection of exogenous adiponectin restored the sensitivity of adipo(-/-) mice to EE-induced behavioral benefits. Interestingly, adiponectin depletion did not prevent the hippocampal neurogenesis induced by EE. Therefore, antidepressant properties of adiponectin are likely to be related to changes in signaling in the hypothalamus rather than through hippocampal-neurogenesis mechanisms. Additionally, EE did not modify the plasma levels of adiponectin but may favor the passage of adiponectin from the blood to the cerebrospinal fluid. Our findings provide advances in the understanding of the anxiolytic and antidepressant-like effects of EE and highlight adiponectin as a pivotal mediator., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Despite several decades of research, current antidepressant (AD) treatments remain of a limited efficacy justifying the need to find new drugs. These drugs have to be more efficacious, more rapid and display lesser side effects. Using rodent models, we recently identified spadin as a new antidepressant molecule that acts more quickly than classical ADs, working within 4 days to get same effects obtained with other ADs after 21 days. Spadin blocks TREK-1 K(2P) potassium channels that are considered as new targets for ADs. Deletion of the TREK-1 channel is known to increase sensitivity to pain, seizures and ischemia. Thus blocking these channels could result in deleterious side effects. In this study we showed that spadin did not interfere with other TREK-1 controlled functions such as pain, epilepsy and ischemia. We also demonstrated that spadin was unable to inhibit currents generated by TREK-2, TRAAK, TASK and TRESK four other K2P channels. More importantly, spadin did not induce cardiac dysfunctions, did not block I(Kr) and I(Ks) and did not modify the systolic pressure or cardiac pulses. After a three week treatment spadin remained an efficacious AD and did not modify the infarct size in brain following focal ischemia. Finally, we showed that kainate induced seizures and glycemia were not modified by spadin treatments. These data, together with those previously published reinforce the idea that spadin represents a good candidate for a new generation of ADs. This article is part of a Special Issue entitled 'Anxiety and Depression'., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Omega-3 polyunsaturated fatty acids are known to have therapeutic potential in several neurological and psychiatric disorders. However, the molecular mechanisms of action underlying these effects are not well elucidated. We previously showed that alpha-linolenic acid (ALA) reduced ischemic brain damage after a single treatment. To follow-up this finding, we investigated whether subchronic ALA treatment promoted neuronal plasticity. Three sequential injections with a neuroprotective dose of ALA increased neurogenesis and expression of key proteins involved in synaptic functions, namely, synaptophysin-1, VAMP-2, and SNAP-25, as well as proteins supporting glutamatergic neurotransmission, namely, V-GLUT1 and V-GLUT2. These effects were correlated with an increase in brain-derived neurotrophic factor (BDNF) protein levels, both in vitro using neural stem cells and hippocampal cultures and in vivo, after subchronic ALA treatment. Given that BDNF has antidepressant activity, this led us to test whether subchronic ALA treatment could produce antidepressant-like behavior. ALA-treated mice had significantly reduced measures of depressive-like behavior compared with vehicle-treated animals, suggesting another aspect of ALA treatment that could stimulate functional stroke recovery by potentially combining acute neuroprotection with long-term repair/compensatory plasticity. Indeed, three sequential injections of ALA enhanced protection, either as a pretreatment, wherein it reduced post-ischemic infarct volume 24 h after a 1-hour occlusion of the middle cerebral artery or as post-treatment therapy, wherein it augmented animal survival rates by threefold 10 days after ischemia.

The temporal relationship between depression and cognitive decline has not been extensively investigated in prospective population-based studies, and most of these have only looked in one direction. We estimated the bidirectional temporal relationship between depressive symptoms and cognitive function in older subjects, excluding subjects with a clinical diagnosis of dementia or mild cognitive impairment (MCI). In a total of 2,963 individuals from the Italian Longitudinal Study on Aging, depressive symptoms, global cognitive function, and episodic memory were measured. Dementia, Alzheimer's disease, vascular dementia, and MCI were classified using current clinical criteria. Depressive symptoms at baseline were associated with an accelerated global cognitive function decline and an accelerated rate of episodic memory delayed recall decline in a 3.5-year follow-up. Finally, an accelerated increase with time of depressive symptoms during the same follow-up period was not associated with global cognitive function and episodic memory (immediate and delayed recall). In older subjects non-cognitively impaired, depressive symptoms at baseline predicted change over time of global cognitive decline and episodic memory delayed recall. Global cognitive function and episodic memory at baseline were not associated with the course of depressive symptoms during the follow-up.

Background: Mild cognitive impairment (MCI) is often a prodromal of dementia and depressive symptoms have been suggested as risk factor for dementing disorders. We evaluated the possible impact of depressive symptoms on the rate of progression to dementia in MCI patients after a 3.5-year follow-up; and the interaction between depressive symptoms and vascular risk factors for conversion to dementia., Methods: A total of 2,963 individuals from a sample of 5,632 65-84 year old subjects were evaluated at the first (1992-1993), and second survey (1995-1996) of the Italian Longitudinal Study on Aging (ILSA), a prospective cohort study. MCI and dementia were classified using current clinical criteria. Depressive symptoms were measured with the Geriatric Depression Scale., Results: Among the 2,963 participants, 139 prevalent MCI patients were diagnosed at the first survey. During the 3.5-year follow-up, 14 MCI patients progressed to dementia, and we did not find any significant relationship between depressive symptoms and rate of progression to dementia (RR 1.42, 95% CI, 0.48-4.23, chi2 0.40, p < 0.53). No socio-demographic variables or vascular risk factors modified the association between depressive symptoms and conversion to dementia., Conclusions: In our population, depressive symptoms were not associated with the rate of progression to dementia in MCI patients. Our findings did not support a role of socio-demographic variables or vascular risk factors in the association of depressive symptoms and conversion to dementia.

Aims: We estimated the prevalence and incidence rates of depressive symptoms and the role of vascular risk factors and sociodemographic variables on the occurrence of depressive symptoms in mild cognitive impairment (MCI)., Methods: In the Italian Longitudinal Study on Aging, 2,963 individuals from 5,632 65- to 84-year-old subjects were evaluated at the 1st and 2nd survey, with a 3.5-year follow-up. Dementia and MCI were classified using current criteria. Depressive symptoms were measured with the Geriatric Depression Scale., Results: Among the 2,963 participants, 139 prevalent MCI cases were diagnosed with a depressive symptoms prevalence rate of 63.3%. During the 3.5-year follow-up, we estimated an incidence rate of depressive symptoms of 29.6 per 100 person-years. No sociodemographic variables or vascular risk factors modified the incidence of depressive symptoms in cognitively stable MCI patients or in MCI patients who reverted to normal cognition., Conclusion: In our population, there was a high prevalence and incidence of depressive symptoms in MCI. Our findings do not provide support for a possible role of vascular risk factors in the development of depressive symptoms in MCI, although these findings were based on relatively few cases of MCI, limiting the capacity to draw definitive conclusions., (Copyright (c) 2007 S. Karger AG, Basel.)

Background. Depression is recognized as being associated with increased mortality. However, there has been little previous research on the impact of longitudinal changes in late-life depressive symptoms on mortality, and of their remission in particular. Method. As part of a prospective, population-based study on a random sample of 5632 subjects aged 65-84 years, with a 10-year follow-up of vital status, depressive symptoms were assessed by the 30-item Italian version of the Geriatric Depression Scale (GDS). The number of participants in the GDS measurements was 3214 at baseline and 2070 at the second survey, 3 years later. Longitudinal changes in depressive symptoms (stable, remitted, worsened) were examined in participants in both evaluations (n = 1941). Mortality hazard ratios (MHRs) according to severity of symptoms and their changes over time were obtained by means of Cox proportional hazards regression models, adjusting for age and other potentially confounding factors. Results. Severity is significantly associated with excess mortality in both genders. Compared to the stability of depressive symptoms, a worsened condition shows a higher 7-year mortality risk [MHR 1.46, 95% confidence interval (CI) 1.15-1.84], whereas remission reduces by about 40% the risk of mortality in both genders (women MHR 0.55, 95% CI 0.32-0.95; men MHR 0.59, 95% CI 0.37-0.93). Neither sociodemographic nor medical confounders significantly modified these associations. Conclusions. Consistent with previous reports, the severity and persistence of depression are associated with higher mortality risks. Our findings extend the magnitude of the association demonstrating that remission of symptoms is related to a significant reduction in mortality, highlighting the need to enhance case-finding and successful treatment of late-life depression. [ABSTRACT FROM AUTHOR]