Comparison of the effects of BDNF/TRKB signalling on metabolic biomarkers in the liver of sedentary and trained rats with normal and knockout BDNF genotypes

Grzelak, Norbert; Kaczmarek, Dominik; Mrówczyński, Włodzimierz

doi:10.3389/fphys.2023.1268648

Front. Physiol.

2023

DOI: 10.3389/fphys.2023.1268648

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Comparison of the effects of BDNF/TRKB signalling on metabolic biomarkers in the liver of sedentary and trained rats with normal and knockout BDNF genotypes

Norbert Grzelak,

Dominik Kaczmarek,

Włodzimierz Mrówczyński

Abstract: Introduction: The effect of brain-derived neurotrophic factor (BDNF) on the modulation of metabolic processes in the liver is poorly understood. Therefore, the aim of this study was to investigate whether hepatic concentrations or activities of metabolic biomarkers depend on altered BDNF/TrkB content in the liver, resulting from different BDNF genotypes of rats. In addition, it was assessed whether 5-week moderate endurance training modifies the levels of BDNF/Trk-B signaling and studied hepatic markers.Method… Show more

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2024

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Cited by 4 publications

References 67 publications

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Ketamine attenuates kidney damage and depression-like behaviors in mice with cisplatin-induced acute kidney injury

Huang,

He,

Cheng

et al. 2024

Transl Psychiatry

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Acute kidney injury (AKI) is a serious condition characterized by decreased urine output, often accompanied by psychiatric symptoms like depression. However, there are limited pharmacological treatments available for AKI and its associated depressive symptoms. In this study, we investigated whether cisplatin-induced AKI in mice leads to depression-like behaviors and whether ketamine could alleviate both the kidney injury and these behaviors. Mice with cisplatin-induced AKI exhibited elevated levels of creatinine and urea, kidney damage, increased kidney injury molecule-1 protein, and pathological changes in the liver, colon, and spleen. They also showed depression-like behaviors and reduced expression of synaptic proteins in the prefrontal cortex. Remarkably, a single dose of ketamine significantly reduced these symptoms and pathological changes. Interestingly, the beneficial effects of ketamine on the kidneys, other organs, and depression-like behaviors, were reversed by the tropomyosin receptor kinase B (TrkB) inhibitor ANA-12. Western blot analysis revealed the involvement of the TrkB and ERK (extracellular signal-regulated kinase)-CREB (cAMP response element binding protein) signaling pathway. Additionally, metabolomics analysis indicated that blood metabolites, such as C16-ceramide, may contribute to the effects of ketamine in this model. These findings suggest that cisplatin-induced nephrotoxicity in AKI mice contributes to depression-like behaviors, and ketamine can alleviate both kidney damage and depression-like symptoms by modulating the TrkB and ERK-CREB signaling pathways, as well as altering blood metabolites. However, the role of the kidney-brain axis in these depression-like behaviors remains unclear. Furthermore, ketamine may have therapeutic potential for treating kidney diseases such as AKI, along with associated depressive symptoms.

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Ketamine attenuates kidney damage and depression-like behaviors in mice with cisplatin-induced acute kidney injury

Huang,

He,

Cheng

et al. 2024

Transl Psychiatry

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Myocardial Disorders in BDNF-Deficient Rats: Limited Recovery Post-Moderate Endurance Training

Grzelak,

Kaczmarek,

Poziemba

et al. 2024

DMSO

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Introduction The study aimed to determine whether heterozygous BDNF-deficient (BDNF-knockout, SD-BDNF) rats exhibit pathological changes in the myocardium and to assess whether a 5-week moderate-intensity endurance training program can reverse adverse changes in the heart muscle. Methods Experiments were conducted on four groups of rats: control wild-type, control BDNF knockout, trained wild-type and trained BDNF knockout. Knockout rats were selected due to the presence of symptoms resembling metabolic syndrome in serum and liver while 5-week moderate endurance training was used as an intervention targeted at restoring heart function. Measurements of BDNF/Trk-B concentrations and molecules levels and activities, such as cardiac specific enzymes like creatine kinase and creatine kinase myocardial band, lipids as total cholesterol, low-density lipoprotein and triglycerides, metabolic enzymes including alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase and lactate dehydrogenase and interleukin-1 were carried out in myocardium homogenates. Results In BDNF-deficient rats, the myocardium showed significantly reduced lipid concentrations, decreased metabolic and cardiac enzyme activity, and elevated Trk-B levels, all of which are indicative of myocardial ischemia or hypoxia. These changes in critical biomarkers were consistent with those earlier observed in the livers of BDNF-deficient rats, suggesting a link between the liver and cardiac function. Moderate endurance training led to an increase in creatine kinase activity in the myocardium of trained rats, suggesting increased production and utilization of energy required for myocardial contraction in trained wild-type and knockout populations of rats. Discussion BDNF-deficient rats exhibited numerous myocardial abnormalities, most of which were not reversible after moderate-intensity endurance training. These findings provide a basis for a deeper understanding of the mechanisms underlying myocardial disorders in BDNF-deficient rats, which appear to be a suitable model for studying various aspects of metabolic disorders.

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The interaction of BDNF with estrogen in the development of hypertension and obesity, particularly during menopause

Zhang,

He,

Pan

et al. 2024

Front. Endocrinol.

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The expression of BDNF in both neuronal and non-neuronal cells is influenced by various stimuli, including prenatal developmental factors and postnatal conditions such as estrogens, dietary habits, and lifestyle factors like obesity, blood pressure, and aging. Central BDNF plays a crucial role in modulating how target tissues respond to these stimuli, influencing the pathogenesis of hypertension, mitigating obesity, and protecting neurons from aging. Thus, BDNF serves as a dynamic mediator of environmental influences, reflecting an individual's unique history of exposure. Estrogens, on the other hand, regulate various processes to maintain overall physiological well-being. Through nuclear estrogen receptors (ERα, ERβ) and the membrane estrogen receptor (GPER1), estrogens modulate transcriptional processes and signaling events that regulate the expression of target genes, such as ERα, components of the renin-angiotensin system (RAS), and hormone-sensitive lipase. Estrogens are instrumental in maintaining the set point for blood pressure and energy balance. BDNF and estrogens work cooperatively to prevent obesity by favoring lipolysis, and counteractively regulate blood pressure to adapt to the environment. Estrogen deficiency leads to menopause in women with low central BDNF level. This review delves into the complex mechanisms involving BDNF and estrogen, especially in the context of hypertension and obesity, particularly among postmenopausal women. The insights gained aim to inform the development of comprehensive therapeutic strategies for these prevalent syndromes affecting approximately 68% of adults.

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Comparison of the effects of BDNF/TRKB signalling on metabolic biomarkers in the liver of sedentary and trained rats with normal and knockout BDNF genotypes

Cited by 4 publications

References 67 publications

Ketamine attenuates kidney damage and depression-like behaviors in mice with cisplatin-induced acute kidney injury

Ketamine attenuates kidney damage and depression-like behaviors in mice with cisplatin-induced acute kidney injury

Myocardial Disorders in BDNF-Deficient Rats: Limited Recovery Post-Moderate Endurance Training

The interaction of BDNF with estrogen in the development of hypertension and obesity, particularly during menopause

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