scholarly journals Oral NF‐κB blockade attenuates pro‐inflammatory cytokines in the hypothalamic paraventricular nucleus of streptozotocin‐induced diabetes

2009 ◽  
Vol 23 (S1) ◽  
Author(s):  
Yu‐Ming Kang ◽  
Jing‐Hui Lei ◽  
Ying Ma ◽  
Zheng Guo ◽  
Yao‐Jun Sun ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Paraventricular Nucleus ◽  
Hypothalamic Paraventricular Nucleus ◽  
Streptozotocin Induced Diabetes ◽  
Pro Inflammatory Cytokines

scholarly journals Three-dimensional morphometric analysis reveals time-dependent structural changes in microglia and astrocytes in the central amygdala and hypothalamic paraventricular nucleus of heart failure rats

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Ferdinand Althammer ◽  
Hildebrando Candido Ferreira-Neto ◽  
Myurajan Rubaharan ◽  
Ranjan K. Roy ◽  
Atit A. Patel ◽  
...  
Keyword(s):  
Heart Failure ◽  
Mood Disorders ◽  
Inflammatory Cytokines ◽  
Paraventricular Nucleus ◽  
Morphometric Analysis ◽  
Three Dimensional ◽  
Hypothalamic Paraventricular Nucleus ◽  
Time Dependent ◽  
Central Amygdala ◽  
Pro Inflammatory Cytokines

Abstract Background Cardiovascular diseases, including heart failure, are the most common cause of death globally. Recent studies support a high degree of comorbidity between heart failure and cognitive and mood disorders resulting in memory loss, depression, and anxiety. While neuroinflammation in the hypothalamic paraventricular nucleus contributes to autonomic and cardiovascular dysregulation in heart failure, mechanisms underlying cognitive and mood disorders in this disease remain elusive. The goal of this study was to quantitatively assess markers of neuroinflammation (glial morphology, cytokines, and A1 astrocyte markers) in the central amygdala, a critical forebrain region involved in emotion and cognition, and to determine its time course and correlation to disease severity during the progression of heart failure. Methods We developed and implemented a comprehensive microglial/astrocyte profiler for precise three-dimensional morphometric analysis of individual microglia and astrocytes in specific brain nuclei at different time points during the progression of heart failure. To this end, we used a well-established ischemic heart failure rat model. Morphometric studies were complemented with quantification of various pro-inflammatory cytokines and A1/A2 astrocyte markers via qPCR. Results We report structural remodeling of central amygdala microglia and astrocytes during heart failure that affected cell volume, surface area, filament length, and glial branches, resulting overall in somatic swelling and deramification, indicative of a change in glial state. These changes occurred in a time-dependent manner, correlated with the severity of heart failure, and were delayed compared to changes in the hypothalamic paraventricular nucleus. Morphometric changes correlated with elevated mRNA levels of pro-inflammatory cytokines and markers of reactive A1-type astrocytes in the paraventricular nucleus and central amygdala during heart failure. Conclusion We provide evidence that in addition to the previously described hypothalamic neuroinflammation implicated in sympathohumoral activation during heart failure, microglia, and astrocytes within the central amygdala also undergo structural remodeling indicative of glial shifts towards pro-inflammatory phenotypes. Thus, our studies suggest that neuroinflammation in the amygdala stands as a novel pathophysiological mechanism and potential therapeutic target that could be associated with emotional and cognitive deficits commonly observed at later stages during the course of heart failure.

scholarly journals Three-dimensional morphometric analysis reveals time-dependent structural changes in microglia and astrocytes in the central amygdala and hypothalamic paraventricular nucleus of heart failure rats

2020 ◽  
Author(s):  
Ferdinand Althammer ◽  
Hildebrando Candido Ferreira-Neto ◽  
Myurajan Rubaharan ◽  
Ranjan Kumer Roy ◽  
javier E Stern
Keyword(s):  
Heart Failure ◽  
Mood Disorders ◽  
Inflammatory Cytokines ◽  
Paraventricular Nucleus ◽  
Morphometric Analysis ◽  
Three Dimensional ◽  
Hypothalamic Paraventricular Nucleus ◽  
Time Dependent ◽  
Central Amygdala ◽  
Pro Inflammatory Cytokines

Abstract Background Cardiovascular diseases, including heart failure are the most common cause of death globally. Recent studies support a high degree of comorbidity between heart failure and cognitive and mood disorders resulting in memory loss, depression and anxiety. While neuroinflammation in the hypothalamic paraventricular nucleus contributes to autonomic and cardiovascular dysregulation in heart failure, mechanisms underlying cognitive and mood disorders in this disease remain elusive. The goal of this study was to quantitatively asses markers of neuroinflammation (glial morphology, cytokines and A1 astrocyte markers) in the central amygdala, a critical forebrain region involved in emotion and cognition, and to determine its time course and correlation to disease severity during the progression of heart failure.Methods We developed and implemented a comprehensive microglial/astrocyte profiler for precise three-dimensional morphometric analysis of individual microglia and astrocytes in specific brain nuclei at different time points during the progression of heart failure. To this end, we used a well-established ischemic heart failure rat model. Morphometric studies were complemented with quantification of various pro-inflammatory cytokines and A1/A2 astrocyte markers via qPCR. Results We report structural remodeling of central amygdala microglia and astrocytes during heart failure that affected cell volume, surface area, filament length and microglial branches, resulting overall in somatic swelling and deramification, indicative of a change in microglial state. These changes occurred in a time-dependent manner, correlated with the severity of heart failure, and were delayed compared to changes in the hypothalamic paraventricular nucleus. Morphometric changes correlated with elevated mRNA levels of pro-inflammatory cytokines and markers of reactive A1-type astrocytes in the paraventricular nucleus and central amygdala during heart failure. Conclusion We provide evidence that in addition to the previously described hypothalamic neuroinflammation implicated in sympathohumoral activation during heart failure, microglia and astrocytes within the central amygdala also undergo structural remodeling indicative of glial shifts towards activated and pro-inflammatory phenotypes, respectively. Thus, our studies suggest that neuroinflammation in the amygdala stands as a novel pathophysiological mechanism and potential therapeutic target for that could be associated with emotional and cognitive deficits commonly observed at later stages during the course of heart failure.

Abstract 113: Cytokines Expression in Hypothalamic Paraventricular Nucleus Account for Cardiovascular Deficits and Improved Functions after Training in Spontaneously Hypertensive Rats.

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Gustavo S Masson ◽  
Tassia S Costa ◽  
Lisete C Michelini
Keyword(s):  
Inflammatory Cytokines ◽  
Paraventricular Nucleus ◽  
Pearson Correlation ◽  
Power Spectral Analysis ◽  
Adaptive Responses ◽  
Spontaneously Hypertensive ◽  
Endogenous Gene ◽  
Power Spectral ◽  
Post Hoc ◽  
Pro Inflammatory Cytokines

Aim: To analyze the sequence of adaptive responses induced by training (T) on both hemodynamic profile and cytokines gene expression within the paraventricular nucleus (PVN). Methods: SHR submitted to T (treadmill, 55% maximal capacity, 1h/day, 5 d/week) or kept sedentary (S), were cannulated for measurement of pressure (BP), heart rate (HR) and baroreflex sensitivity (BrS) at rest on weeks 0, 1, 2, 4 and 8 of protocols. HR and BP variability (power spectral analysis) were also evaluated. After euthanasia, brains were removed for isolation of PVN. Total mRNA was extracted for quantification of TNFα and IL-6 expression by real time PCR (HPRT as the endogenous gene). WKY were used as time controls. One-way ANOVA, with Fisher post-hoc test and Pearson correlation were employed. Results: At the beginning of the protocols, SHR exhibited high mean BP and HR, decreased BrS, increased BP variability and decreased HR variability (170±3 mmHg, 356±7 b/min; 2.3±0.2 b/min/mmHg, 14±2 mmHg 2 and 14±2 ms 2 ) when compared to WKY (119±2 mmHg, 307±6 b/min; 3.6±0.3 b/min/mmHg, 6±1 mmHg 2 and 22±2 ms 2 , respectively). Pro-inflammatory cytokines expression in PVN are also elevated in SHR vs WKY (TNF-α= 1.9±0.3 vs 1.2±0.1, IL-6= 4.9±0.8 vs 1.1±0.3 UA). In the SHR, T caused significant increases on BrS (4.0±0.2 b/min/mmHg, T 2 -T 8 ), HR variability (21±1 ms 2 , with a 60% increase of HF component from T 4 -T 8 ) and prevented the increase on BP variability in the SHR (13±2 vs 20±3 mmHg 2 , T 8 vs S 8 , with 29% reduction of LF component at T 8 ). T caused a prompt normalization of TNFα and IL-6 mRNA expression within the PVN (1.3±0.2 and 0.9±2 UA at T 2 ), accompanied by HR reduction (338±4 b/min, T 4 -T 8 ) and mean BP fall (159±6 mmHg, T 8 ), with significant correlations between TNFα x HR variability (Y=-3.6x+24.3, r= -0.29; P=0.04), TNFα x BrS (Y=-0.7x+4.3, r=-0.35; P=0.01), TNFα x BP (Y=9x+140, r= 0.26; P=0.04) and TNFα x HR (Y=18x+309, r= 0.29; P=0.03). PVN IL-6 content was also correlated with HR variability (Y=-1.8x+21.5, r=-0.36; P=0.01), BrS (Y= -0.3x+4.2, r=-0.44; P<0.001) and HR (Y=7x+324, r=0.30; P=0.02). Conclusions: Data suggested the involvement of PVN pro-inflammatory cytokines in the mediation of cardiovascular deficits in the SHR and the efficacy of T to prompt normalize these deleterious effects.

Blunted endogenous GABA-mediated inhibition in the hypothalamic paraventricular nucleus of rats with streptozotocin-induced diabetes

2012 ◽  
Vol 113 (3) ◽  
pp. 319-325 ◽  
Author(s):  
Zurina Hassan ◽  
Munavvar Zubaid Abdul Sattar ◽  
Farah Wahida Suhaimi ◽  
Nurul Hasnida Mohammed Yusoff ◽  
Mohammed H. Abdulla ◽  
...  
Keyword(s):  
Paraventricular Nucleus ◽  
Hypothalamic Paraventricular Nucleus ◽  
Endogenous Gaba ◽  
Streptozotocin Induced Diabetes

Pro-inflammatory cytokines in the paraventricular nucleus mediate the adipose afferent reflex in rats

2020 ◽  
Vol 472 (3) ◽  
pp. 343-354 ◽  
Author(s):  
Peng Lu ◽  
Li-wen Liang ◽  
Ai-li Xu ◽  
Ye-ying Sun ◽  
Shu-jun Jiang ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Paraventricular Nucleus ◽  
Pro Inflammatory Cytokines
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