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.

scholarly journals Androgen-Dependent Regulation of Brain-Derived Neurotrophic Factor and Tyrosine Kinase B in the Sexually Dimorphic Spinal Nucleus of the Bulbocavernosus

Endocrinology ◽  
2007 ◽  
Vol 148 (8) ◽  
pp. 3655-3665 ◽  
Author(s):  
Erich N. Ottem ◽  
Laurel A. Beck ◽  
Cynthia L. Jordan ◽  
S. Marc Breedlove
Keyword(s):  
Adult Male ◽  
Neurotrophic Factor ◽  
Dendritic Structure ◽  
Brain Derived Neurotrophic Factor ◽  
Male Rats ◽  
Sexually Dimorphic ◽  
Spinal Nucleus ◽  
Androgen Effects ◽  
Tyrosine Receptor Kinase

Castration of adult male rats causes the dendrites of androgen-sensitive motoneurons of the spinal nucleus of the bulbocavernosus (SNB) to retract. Brain-derived neurotrophic factor (BDNF), via activation of tyrosine receptor kinase B (trkB), has been implicated in mediating androgen effects on SNB dendrites. We used in situ hybridization to demonstrate that SNB motoneurons in gonadally intact adult male rats contain mRNA for both BDNF and trkB. Two weeks after gonadectomy, both transcripts were significantly decreased in SNB motoneurons but not in the non-androgen-responsive motoneurons of the adjacent retrodorsolateral nucleus (RDLN). In a second experiment, target perineal and foot muscles of SNB and RDLN motoneurons, respectively, were injected with the retrograde tracer Fluorogold, and then immunocytochemistry was performed to examine the distribution of BDNF and trkB proteins in SNB and RDLN motoneurons and their glutamatergic afferents. Confocal analysis revealed that gonadectomy induces a loss of BDNF protein in SNB dendrites but not in RDLN dendrites. Testosterone treatment of castrates prevented the loss of BDNF from SNB dendrites. Confocal analysis also revealed trkB protein in SNB and RDLN dendrites and in their glutamatergic afferents. Gonadectomy had no discernable effect on trkB protein in SNB or RDLN motoneurons or in their glutamatergic afferents. These results suggest that androgen maintains a BDNF-signaling pathway in SNB motoneurons that may underlie the maintenance of dendritic structure and synaptic signaling.

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.

scholarly journals ANTINEURODEGENERATIVE ACTIVITY OF MICROALGAE DUNALIELLA SALINA IN RATS WITH ALZHEIMER’S DISEASE

2016 ◽  
Vol 10 (1) ◽  
pp. 134 ◽  
Author(s):  
Farouk Kamel Elbaz ◽  
Hanan F Aly ◽  
Wagdy Kb Khalil ◽  
Hoda F Booles ◽  
Gamila H Al
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurotrophic Factor ◽  
Dunaliella Salina ◽  
Brain Derived Neurotrophic Factor ◽  
Male Rats ◽  
Paraoxonase 1 ◽  
Pon1 Activity ◽  
The Brain ◽  
Antioxidant Effects

ABSTRACTObjective: The present study is aimed to investigate the promising action of Dunaliella salina extract as a natural protector against Alzheimer’sdisease (AD) and reported to possess a variety of activities, including antioxidant effects due to its ability to create large amount of carotenoids.Methods: D. salina is a type of halophile green microalgae was used in the present study. 50 male rats were used in this study, where aluminumchloride was orally administered to induce AD in a dose of 100 mg/kg, daily for 6 weeks. Al-intoxicated rats treated orally daily with D. salinaethanolic extract for 6 weeks in a dose of 150 mg/kg b.wt., whereas standard anti-Alzheimer drug donepezil tartrate was administered at the doseof 10 mg/kg b.wt./day for 6 consecutive weeks. The anti-Alzheimer properties of D. salina extract were achieved through measuring the calmodulin(CaM) level, paraoxonase 1 (PON1) activity, the antiapoptotic marker (Bcl2), brain-derived neurotrophic factor (BDNF), the generation of the DNAadducts (8-hydroxy-2-deoxyguanosine [8-OHdG]/2-deoxy guanosine [2-dG]), and alteration in the expression of amyloid precursor protein, β-siteAPP-cleaving enzyme 1 (BACE1), and β-site APP-cleaving enzyme 2 (BACE2) in AD rats.Results: The current results demonstrated that supplementation of AD rats with D. salina extract-enhanced CaM level, and increased PON1 activity,upregulated Bcl2 and BDNF, decreased the levels of DNA adducts (8-OHdG/2-dG), and suppressed the alterations of the expression levels of APP,BACE1, and BACE2-m RNAs as compared with those in AD rats.Conclusion: It could be concluded that the biological activity of D. salina extract might be regulated by 9-cis b-carotene protecting the brain cells fromthe oxidative stress in AD rats.Keywords: Dunaliella salina, Calmodulin, Paraoxonase 1, Bcl2, Brain-derived neurotrophic factor, Alzheimer’s disease, DNA adduct, Amyloid precursorprotein.

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