scholarly journals Influence of brain-derived neurotrophic factor-tyrosine receptor kinase B signalling in the nucleus tractus solitarius on baroreflex sensitivity in rats with chronic heart failure

2016 ◽  
Vol 594 (19) ◽  
pp. 5711-5725 ◽  
Author(s):  
Bryan K. Becker ◽  
Changhai Tian ◽  
Irving H. Zucker ◽  
Han-Jun Wang
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Neurotrophic Factor ◽  
Baroreflex Sensitivity ◽  
Nucleus Tractus Solitarius ◽  
Brain Derived Neurotrophic Factor ◽  
Receptor Kinase ◽  
Tyrosine Receptor Kinase

Abstract 210: Impaired Brain-Derived Neurotrophic Factor-TrkB Signaling in Nucleus Tractus Solitarius During Chronic Heart Failure Blunts Baroreflex Sensitivity

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Bryan K Becker ◽  
Hanjun Wang ◽  
Irving H Zucker
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Neurotrophic Factor ◽  
Baroreflex Sensitivity ◽  
Nucleus Tractus Solitarius ◽  
Critical Role ◽  
Brain Derived Neurotrophic Factor ◽  
Central Target ◽  
Autonomic Imbalance ◽  
Baroreflex Function

Blunted baroreflex function is a negatively prognostic marker of autonomic imbalance in chronic heart failure (CHF), yet the mechanisms underlying baroreflex blunting in CHF are not fully understood. The nucleus tractus solitarius (NTS) is the primary central target of baroreceptor afferents, and plays a critical role in regulating central baroreflex sensitivity. Brain-derived neurotrophic factor (BDNF) and its receptor, TrkB, are highly expressed in the NTS, but little is known about the role of BDNF signaling in the NTS. We hypothesized that in the NTS, BDNF enhances baroreflex sensitivity, and impaired BDNF-TrkB signaling contributes to the blunted baroreflex function in CHF. To test this hypothesis, 50 nl of BDNF or the selective TrkB antagonist ANA-12 were microinjected bilaterally into the dorso-medial NTS of sham-operated rats and myocardial infarct-induced CHF rats. BDNF evoked a greater decrease in blood pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA) in sham vs. CHF rats. Injection of ANA-12 increased MAP, HR, and RSNA to a greater extent in sham vs. CHF rats (Table). Following 125 μM ANA-12, baroreflex sensitivity was blunted in sham rats (3.7 ± 0.3 vs. 1.9 ± 0.1 bpm/mmHg max gain, p < .05 before vs. after, n = 4). CHF rats had blunted baroreflex sensitivity vs. sham (2.3 ± 0.1 bpm/mmHg, p < .05, n = 4), and ANA-12 had little effect on baroreflex sensitivity in CHF (2.0 ± 0.1 bpm/mmHg, n = 4). These data suggest that endogenous BDNF plays an important role in maintaining baroreflex sensitivity in the NTS, and that BDNF-TrkB signaling is impaired in CHF, which may contribute to blunted baroreflex sensitivity and autonomic imbalance.

Additive clinical value of serum brain-derived neurotrophic factor for prediction of chronic heart failure outcome

2015 ◽  
Vol 31 (4) ◽  
pp. 535-544 ◽  
Author(s):  
Shinpei Kadowaki ◽  
Tetsuro Shishido ◽  
Yuki Honda ◽  
Taro Narumi ◽  
Yoichiro Otaki ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Neurotrophic Factor ◽  
Brain Derived Neurotrophic Factor ◽  
Clinical Value

scholarly journals Brain-Derived Neurotrophic Factor and Supraoptic Vasopressin Neurons in Hyponatremia

2019 ◽  
Vol 110 (7-8) ◽  
pp. 630-641
Author(s):  
Kirthikaa Balapattabi ◽  
Joel T. Little ◽  
Martha Bachelor ◽  
J. Thomas Cunningham
Keyword(s):  
Liver Failure ◽  
Neurotrophic Factor ◽  
Plasma Osmolality ◽  
Liver Weight ◽  
Brain Derived Neurotrophic Factor ◽  
Male Rats ◽  
Receptor Kinase ◽  
Control Shrna ◽  
Vasopressin Neurons ◽  
Tyrosine Receptor Kinase

Hyponatremia due to elevated arginine vasopressin (AVP) secretion increases mortality in liver failure patients. The mechanisms causing dysregulation of AVP secretion are unknown. Our hypothesis is that inappropriate AVP release associated with liver failure is due to increased brain-derived neurotrophic factor (BDNF) in the supraoptic nucleus (SON). BDNF diminishes GABAA inhibition in SON AVP neurons by increasing intracellular chloride through tyrosine receptor kinase B (TrkB) activation and downregulation of K+/Cl– cotransporter 2 (KCC2). This loss of inhibition could increase AVP secretion. This hypothesis was tested using shRNA against BDNF (shBDNF) in the SON in bile duct ligated (BDL) male rats. All BDL rats had significantly increased liver weight (p < 0.05; 6–9) compared to shams. BDL rats with control ­shRNA injections (BDL scrambled [SCR]) developed hyponatremia with increased plasma AVP and copeptin (CPP; all p < 0.05; 6–9) compared to sham groups. This is the first study to show that phosphorylation of TrkB is significantly increased along with significant decrease in phosphorylation of KCC2 in BDL SCR rats compared to the sham rats (p < 0.05;6–8). Knockdown of BDNF in the SON of BDL rats (BDL shBDNF) significantly increased plasma osmolality and hematocrit compared to BDL SCR rats (p < 0.05; 6–9). The BDL shBDNF rats had significant (p < 0.05; 6–9) decreases in plasma AVP and CPP concentration compared to BDL SCR rats. The BDNF knockdown also significantly blocked the increase in TrkB phosphorylation and decrease in KCC2 phosphorylation (p < 0.05; 6–8). The results indicate that BDNF produced in the SON contributes to increased AVP secretion and hyponatremia during liver failure.

Reduced brain-derived neurotrophic factor is associated with cognitive dysfunction in patients with chronic heart failure

2017 ◽  
Vol 17 (5) ◽  
pp. 852-854 ◽  
Author(s):  
Hideaki Suzuki ◽  
Yasuharu Matsumoto ◽  
Hideki Ota ◽  
Koichiro Sugimura ◽  
Jun Takahashi ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Cognitive Dysfunction ◽  
Neurotrophic Factor ◽  
Brain Derived Neurotrophic Factor

miR-124 antagonizes the antidepressant-like effects of standardized gypenosides in mice

2018 ◽  
Vol 32 (4) ◽  
pp. 458-468 ◽  
Author(s):  
Li-Tao Yi ◽  
Rong-Hao Mu ◽  
Shu-Qi Dong ◽  
Shuang-Shuang Wang ◽  
Cheng-Fu Li ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Neurotrophic Factor ◽  
Glucocorticoid Receptors ◽  
Brain Derived Neurotrophic Factor ◽  
Sucrose Preference ◽  
Mild Stress ◽  
Dependent Manner ◽  
Receptor Kinase ◽  
Immobility Time ◽  
Tyrosine Receptor Kinase

Our previous study demonstrated that gypenosides produced antidepressant-like effects in mice exposed to chronic mild stress in a brain-derived neurotrophic factor-dependent manner. However, whether other mechanisms are involved in the antidepressant-like effects of gypenosides is not clear. miR-124 is one of the most abundant microRNAs in the hippocampus, and its dysregulation is related to the pathophysiology of depression. The glucocorticoid receptor is dysfunctional in depression, and it is a direct target of miR-124. Therefore, the present study used corticosterone-induced mice as a model to evaluate the role of miR-124 on the antidepressant-like effects of gypenosides. miR-124 agomir was intracerebrally injected prior to administration of gypenosides and corticosterone injection. Sucrose preference and forced swimming tests were performed 21 days later. Proteins related to glucocorticoid receptors and brain-derived neurotrophic factor-tyrosine receptor kinase B signaling in the hippocampus were evaluated. Our results demonstrated that gypenosides reversed the chronic corticosterone injection-induced decreased sucrose preference and increased immobility time. In contrast, this effect was antagonized by miR-124 injection. In addition, gypenosides increased glucocorticoid receptor and tyrosine receptor kinase B expression in the hippocampus, which activated brain-derived neurotrophic factor signaling. miR-124 also blocked these effects. In conclusion, this study demonstrated that a reduction in miR-124 was required for the antidepressant-like effects of gypenosides induced by chronic corticosterone injection in mice.

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