Evidence for Sustained Elevation of IL-6 in the CNS as a Key Contributor of Depressive-Like Phenotypes.

Evidence for sustained elevation of IL-6 in the CNS as a key contributor of depressive-like phenotypes.

Filed under: Depression Treatment

Transl Psychiatry. 2012; 2: e199
Sukoff Rizzo SJ, Neal SJ, Hughes ZA, Beyna M, Rosenzweig-Lipson S, Moss SJ, Brandon NJ

There is compelling clinical literature implicating a role for cytokines in the pathophysiology of major depressive disorder (MDD). Interleukin-6 (IL-6) and interleukin-1? (IL-1?) are pleiotropic inflammatory cytokines that have been reported to be elevated in patients with MDD. The present studies were undertaken to investigate the relationship between IL-6 and IL-1? in animal models of depressive-like behavior. Analysis of brain tissue homogenates in the cortex of rats subjected to chronic stress paradigms revealed elevated levels of IL-6 protein in the absence of elevations in IL-1?. Central administration of recombinant mouse IL-6 produced depressive-like phenotypes in mice, which were not accompanied by IL-1?-induced increases in the brain tissue or IL-1?-related sickness behavior typical of a general central nervous system inflammatory response. Systemic administration of fluoxetine in the presence of centrally administered IL-6 failed to produce the expected antidepressant-like response in mice relative to sham-infused controls. Further, administration of fluoxetine to mice with endogenous overexpression of brain IL-6 (MRL/MpJ-Fas(LPR/LPR) (LPR mice)) failed to produce the expected antidepressant-like effect relative to fluoxetine-treated control mice (MRL/MpJ(+/+)). Interestingly, blockade of IL-6 trans-signaling by coadministration of a gp130/Fc monomer or an anti-mouse IL-6 antibody with IL-6 prevented the IL-6-induced increases in immobility time as well as attenuated IL-6-induced increases of protein in the cortex. Taken together, these data indicate that elevations in IL-6 may have a pathophysiological role underlying depression and more specifically resistance to current classes of antidepressant medications and suggest that modulation of the IL-6 signaling pathway may have therapeutic potential for treatment-resistant depression.
HubMed – depression


Altered Concentrations of Amyloid Precursor Protein Metabolites in the Cerebrospinal Fluid of Patients with Bipolar Disorder.

Filed under: Depression Treatment

Neuropsychopharmacology. 2012 Nov 6;
Jakobsson J, Zetterberg H, Blennow K, Johan Ekman C, Johansson AG, Landén M

Bipolar disorder is a psychiatric disorder characterized by recurrent episodes of mania/hypomania and depression. Progressive cognitive dysfunction such as impairments in executive function and verbal memory is common in euthymic bipolar patients. The cerebrospinal fluid has previously been used to study neurodegenerative processes in Alzheimer’s disease, from which changes in three core biomarkers have emerged as indicative of degeneration: amyloid ?, total tau, and hyperphosphorylated tau. Here, neurodegeneration in bipolar disorder was investigated by assessing the association between bipolar disorder and cerebrospinal fluid biomarkers for neurodegenerative processes. Cerebrospinal fluid was obtained from 139 bipolar disorder patients and 71 healthy controls. Concentrations of total and phosphorylated tau, amyloid ?1-42, amyloid ?38/?40/?42, and the soluble forms of amyloid precursor protein were measured in patients vs controls. The concentrations of the soluble forms of amyloid precursor protein were significantly lower in bipolar patients compared with controls. The amyloid ?42/amyloid ?38 and the amyloid ?42/amyloid ?40 ratios were higher in bipolar patients than controls. There were no discernible differences in the concentrations of total/phosphorylated tau, amyloid ?1-42, or amyloid ?38/?40/?42. The concentrations of the biomarkers within the bipolar patient group were further associated with different ongoing medical treatments and diagnostic subgroups. The findings suggest that the amyloid precursor protein metabolism is altered in bipolar disorder. The results may have implications for the understanding of the pathophysiology of bipolar disorder and for the development of treatment strategies. Importantly, there were no signs of an Alzheimer-like neurodegenerative process among bipolar patients.Neuropsychopharmacology advance online publication, 5 December 2012; doi:10.1038/npp.2012.231.
HubMed – depression


That’s hot: golden spiny mice display torpor even at high ambient temperatures.

Filed under: Depression Treatment

J Comp Physiol B. 2012 Dec 2;
Grimpo K, Legler K, Heldmaier G, Exner C

Golden spiny mice (Acomys russatus) living in the Judean desert are exposed to extended periods of food and water shortage. We investigated their thermal and metabolic response to three weeks of 50 % food reduction at ambient temperatures of 23, 27, 32 and 35 °C by long term records of metabolic rate and body temperature in the laboratory. At all ambient temperatures, A. russatus responded to starvation by a reduction of daily energy expenditure. At 32 and 35 °C, this metabolic adjustment fully compensated the reduced food availability and they maintained their energy balance at a slightly reduced body mass. At lower ambient temperatures, they could not fully compensate for the reduced food availability and kept a negative energy balance. The reduction of daily energy expenditure was largely achieved by the occurrence of daily torpor. Torpor even occurred at high ambient temperatures of 32 and 35 °C during which metabolic depression was not associated with a marked decrease of body temperature. The results show that the occurrence of daily torpor is not necessarily linked to cold exposure and the development of a pronounced hypothermia, but may even occur as depression of metabolic rate in a hot environment.
HubMed – depression


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