TY - GEN
T1 - Effects of antipsychotic treatment on macrophagic activation in the adipose tissue
AU - Mondelli, Valeria
AU - Calevro, Anita
AU - Cotel, Marie-Caroline
AU - Kapur, Shitij
AU - Pariante, Carmine M.
AU - Vernon, Anthony
PY - 2016/9
Y1 - 2016/9
N2 - Introduction: Antipsychotic medications have been recently suggested to influence immune activation both in the periphery and central nervous system (CNS). However, the effect of chronic antipsychotic treatment on peripheral tissue such adipose tissue remains still unclear. Adipose tissue is known to play an important role in the development of systemic inflammation and mitochondrial dysfunction which can lead to insulin insensitivity and metabolic dysregulation typically present in obesity (Bournat et al., 2010). Macrophages in the adipose tissue display several phenotypic markers including F4/80+. Translocator Protein, TSPO, is a mitochondrial membrane protein which has been recently considered a marker of neuroinflammation as its density is elevated in activated microglia, but its expression has not been yet studied in adipose tissue. In this study we looked at the expression of F4/80+, TSPO, and inflammatory cytokines in rat adipose tissue following chronic antipsychotic treatment. Our aim was to look at the presence of inflammation in the periphery as the same rats previously had shown microglial activation in the brain.
Methods: We collected visceral adipose tissue from a group of 24 male Sprague-Dawley ratstreated in a previous study (Mondelli et al., 2013; Cotel et al., 2015) with vehicle (n = 8), haloperidol (2 mg kg per day, n = 8), or olanzapine (10 mg kg per day, n = 8), using osmotic minipumps, for 8 weeks. We assessed levels of the following pro- and anti-inflammatory cytokines in the adipose tissue: tumor necrosis factor-α (TNFα), interleukin (IL)-1β, IL-6, IL-5, IL-4, IL-10 and KC/GRO, a chemokine (CXC) also known as CXCL1. Cytokine levels were measured using a electrochemiluminescence immunoassay MSD Mesoscale. We performed Western Blot analysis using TSPO antibody and F4/80+ antibody; beta-actin was used for housekeeping expression. The density of the bands was calculated using ImageJ program.
Results: Amongst the cytokines, only IL-6 was significantly up-regulated in olanzapine animals compared to vehicle animals (One-Way ANOVA with Bonferroni post hoc test p < 0.05). Interestingly, the olanzapine group showed also a trend (t-test p = 0.06) for higher F4/80+ when compared with vehicle (mean ± SD: 0.95 ± 0.06 vs 0.80 ± 0.04 respectively). We did not find any significant difference in TSPO expression either between haloperidol and vehicle or between olanzapine and vehicle (t-test: p = 0.3 and p = 0.1 respectively).
Conclusions: Our preliminary results suggest a possible increased inflammation and macrophagic activation in the adipose tissue following olanzapine (based on the IL-6 and F4/80+ data) but not haloperidol treatment. These findings suggest that olanzapine tends to increase/activate inflammation in the adipose tissue with possible important consequences in terms of metabolic dysregulation.
AB - Introduction: Antipsychotic medications have been recently suggested to influence immune activation both in the periphery and central nervous system (CNS). However, the effect of chronic antipsychotic treatment on peripheral tissue such adipose tissue remains still unclear. Adipose tissue is known to play an important role in the development of systemic inflammation and mitochondrial dysfunction which can lead to insulin insensitivity and metabolic dysregulation typically present in obesity (Bournat et al., 2010). Macrophages in the adipose tissue display several phenotypic markers including F4/80+. Translocator Protein, TSPO, is a mitochondrial membrane protein which has been recently considered a marker of neuroinflammation as its density is elevated in activated microglia, but its expression has not been yet studied in adipose tissue. In this study we looked at the expression of F4/80+, TSPO, and inflammatory cytokines in rat adipose tissue following chronic antipsychotic treatment. Our aim was to look at the presence of inflammation in the periphery as the same rats previously had shown microglial activation in the brain.
Methods: We collected visceral adipose tissue from a group of 24 male Sprague-Dawley ratstreated in a previous study (Mondelli et al., 2013; Cotel et al., 2015) with vehicle (n = 8), haloperidol (2 mg kg per day, n = 8), or olanzapine (10 mg kg per day, n = 8), using osmotic minipumps, for 8 weeks. We assessed levels of the following pro- and anti-inflammatory cytokines in the adipose tissue: tumor necrosis factor-α (TNFα), interleukin (IL)-1β, IL-6, IL-5, IL-4, IL-10 and KC/GRO, a chemokine (CXC) also known as CXCL1. Cytokine levels were measured using a electrochemiluminescence immunoassay MSD Mesoscale. We performed Western Blot analysis using TSPO antibody and F4/80+ antibody; beta-actin was used for housekeeping expression. The density of the bands was calculated using ImageJ program.
Results: Amongst the cytokines, only IL-6 was significantly up-regulated in olanzapine animals compared to vehicle animals (One-Way ANOVA with Bonferroni post hoc test p < 0.05). Interestingly, the olanzapine group showed also a trend (t-test p = 0.06) for higher F4/80+ when compared with vehicle (mean ± SD: 0.95 ± 0.06 vs 0.80 ± 0.04 respectively). We did not find any significant difference in TSPO expression either between haloperidol and vehicle or between olanzapine and vehicle (t-test: p = 0.3 and p = 0.1 respectively).
Conclusions: Our preliminary results suggest a possible increased inflammation and macrophagic activation in the adipose tissue following olanzapine (based on the IL-6 and F4/80+ data) but not haloperidol treatment. These findings suggest that olanzapine tends to increase/activate inflammation in the adipose tissue with possible important consequences in terms of metabolic dysregulation.
U2 - 10.1016/j.psyneuen.2016.07.183
DO - 10.1016/j.psyneuen.2016.07.183
M3 - Other contribution
VL - 71
PB - Elsevier
CY - Psychoneuroendocrinology
ER -