scholarly journals A developmental stage- and Kidins220-dependent switch in astrocyte responsiveness to brain-derived neurotrophic factor

2021 ◽  
Author(s):  
Fanny Jaudon ◽  
Martina Albini ◽  
Stefano Ferroni ◽  
Fabio Benfenati ◽  
Fabrizia Cesca
Keyword(s):  
Nervous System ◽  
Neurotrophic Factor ◽  
Brain Derived Neurotrophic Factor ◽  
Embryonic Cells ◽  
Inwardly Rectifying Potassium Channel ◽  
Complex Functions ◽  
The Central Nervous System ◽  
Homeostatic Function ◽  
Neurotrophin Signaling ◽  
Neuronal Physiology

Astroglial cells are key to maintain nervous system homeostasis. Neurotrophins are known for their pleiotropic effects on neuronal physiology, but also exert complex functions onto glial cells. In this work, we investigated: (i) the signaling competence of embryonic and postnatal primary cortical astrocytes exposed to brain-derived neurotrophic factor (BDNF); and (ii) the role of Kinase D interacting substrate (Kidins220), a transmembrane scaffold protein that mediates neurotrophin signaling in neurons, in the astrocyte response to BDNF. We found a shift from a kinase-based response in embryonic cells to a predominantly [Ca2+]i-based response in postnatal cultures associated with the decreased expression of the full-length BDNF receptor TrkB, with a contribution of Kidins220 to the BDNF-activated kinase and [Ca2+]i pathways. Finally, Kidins220 participates in astrocytes’ homeostatic function by controlling the expression of the inwardly rectifying potassium channel (Kir) 4.1 and the metabolic balance of embryonic astrocytes. Overall, our data contribute to the understanding of the complex role played by astrocytes within the central nervous system and identify Kidins220 as a novel actor in the increasing number of pathologies characterized by astrocytic dysfunctions.

scholarly journals A developmental stage- and Kidins220/ARMS-dependent switch in astrocyte responsiveness to brain-derived neurotrophic factor

2021 ◽  
Author(s):  
Fanny Jaudon ◽  
Martina Albini ◽  
Stefano Ferroni ◽  
Fabio Benfenati ◽  
Fabrizia Cesca
Keyword(s):  
Nervous System ◽  
Neurotrophic Factor ◽  
Intracellular Signaling ◽  
Transmembrane Protein ◽  
Brain Derived Neurotrophic Factor ◽  
Embryonic Cells ◽  
The Central Nervous System ◽  
Homeostatic Function ◽  
Membrane Spanning ◽  
Neurotrophin Signaling

ABSTRACTAstroglial cells are key to maintain nervous system homeostasis, as they are able to perceive a wide variety of extracellular signals and to transduce them into responses that may be protective or disruptive toward neighboring neurons through the activation of distinct signaling pathways. Neurotrophins are a family of growth factors known for their pleiotropic effects on neuronal survival, maturation and plasticity. In this work, we investigated: (i) the signaling competence of embryonic and postnatal primary cortical astrocytes exposed to brain-derived neurotrophic factor (BDNF); and (ii) the role of the scaffold protein Kinase D interacting substrate/ankyrin repeat-rich membrane spanning (Kidins220/ARMS), a transmembrane protein that mediates neurotrophin signaling in neurons, in the astrocyte response to BDNF. We found a shift from a kinase-based response in embryonic cells to a predominantly [Ca2+]i-based response in postnatal cultures associated with the decreased expression of the full-length BDNF receptor TrkB. We also found that Kidins220/ARMS contributes to the BDNF-activated intracellular signaling in astrocytes by potentiating both kinase and [Ca2+]i pathways. Finally, Kidins220/ARMS contributes to astrocytes’ homeostatic function by controlling the expression of the inwardly rectifying potassium channel (Kir) 4.1. Overall, our data contribute to the understanding of the complex role played by astrocytes within the central nervous system and identify Kidins220/ARMS as a novel actor in the increasing number of pathologies characterized by astrocytes’ dysfunctions.

scholarly journals Brain-derived Neurotrophic Factor Regulates Energy Expenditure Through the Central Nervous System in Obese Diabetic Mice

2001 ◽  
Vol 2 (3) ◽  
pp. 201-209 ◽  
Author(s):  
Takeshi Nonomura ◽  
Atsushi Tsuchida ◽  
Michiko Ono-Kishino ◽  
Tsutomu Nakagawa ◽  
Mutsuo Taiji ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Blood Glucose ◽  
Energy Expenditure ◽  
Neurotrophic Factor ◽  
Brain Derived Neurotrophic Factor ◽  
Central Administration ◽  
Interscapular Brown Adipose Tissue ◽  
Brown Adipose ◽  
The Central Nervous System

It has been previously demonstrated that brain-derived neurotrophic factor (BDNF) regulates glucose metabolism and energy expenditure in rodent diabetic models such as C57BL/KsJ-leprdb/leprdb(db/db) mice. Central administration of BDNF has been found to reduce blood glucose indb/dbmice, suggesting that BDNF acts through the central nervous system. In the present study we have expanded these investigations to explore the effect of central administration of BDNF on energy metabolism. Intracerebroventricular administration of BDNF lowered blood glucose and increased pancreatic insulin content ofdb/dbmice compared with vehicle-treated pellet pair-feddb/dbmice. While body temperatures of the pellet pair-feddb/dbmice given vehicle were reduced because of restricted food supply in this pair-feeding condition, BDNF treatment remarkably alleviated the reduction of body temperature suggesting the enhancement of thermogenesis. BDNF enhanced norepinephrine turnover and increased uncoupling protein-1 mRNA expression in the interscapular brown adipose tissue. Our evidence indicates that BDNF activates the sympathetic nervous systemviathe central nervous system and regulates energy expenditure in obese diabetic animals.

scholarly journals Brain-derived neurotrophic factor as a potential therapeutic tool in the treatment of nervous system disorders

2020 ◽  
Vol 74 ◽  
pp. 517-531
Author(s):  
Wioletta Kazana ◽  
Agnieszka Zabłocka
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neurotrophic Factor ◽  
Intracellular Transport ◽  
Brain Derived Neurotrophic Factor ◽  
Nerve Cells ◽  
The Body ◽  
Bdnf Level ◽  
The Central Nervous System ◽  
The Brain

Brain-derived neurotrophic factor (BDNF) plays an important role in the proper functioning of the nervous system. It regulates the growth and survival of nerve cells, and is crucial in processes related to the memory, learning and synaptic plasticity. Abnormalities related to the distribution and secretion of BDNF protein accompany many diseases of the nervous system, in the course of which a significant decrease in BDNF level in the brain is observed. Impairments of BDNF transport may occur, for example, in the event of a single nucleotide polymorphism in the Bdnf (Val66Met) coding gene or due to the dysfunctions of the proteins involved in intracellular transport, such as huntingtin (HTT), huntingtin-associated protein 1 (HAP1), carboxypeptidase E (CPE) or sortilin 1 (SORT1). One of the therapeutic goals in the treatment of diseases of the central nervous system may be the regulation of expression and secretion of BDNF protein by nerve cells. Potential therapeutic strategies are based on direct injection of the protein into the specific region of the brain, the use of viral vectors expressing the Bdnf gene, transplantation of BDNF-producing cells, the use of substances of natural origin that stimulate the cells of the central nervous system for BDNF production, or the use of molecules activating the main receptor for BDNF – tyrosine receptor kinase B (TrkB). In addition, an appropriate lifestyle that promotes physical activity helps to increase BDNF level in the body. This paper summarizes the current knowledge about the biological role of BDNF protein and proteins involved in intracellular transport of this neurotrophin. Moreover, it presents contemporary research trends to develop therapeutic methods, leading to an increase in the level of BDNF protein in the brain.

scholarly journals The Role of Brain-Derived Neurotrophic Factor in Epileptogenesis: an Update

2021 ◽  
Vol 12 ◽  
Author(s):  
Xinyi Wang ◽  
Zhe Hu ◽  
Kai Zhong
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neurotrophic Factor ◽  
Neurological Diseases ◽  
Brain Derived Neurotrophic Factor ◽  
The World ◽  
The Central Nervous System ◽  
Spontaneous Recurrent Seizures ◽  
New Evidence

Epilepsy, which is characterized by spontaneous recurrent seizures, is one of the most common and serious chronic neurological diseases in the world. 30% patients failed to control seizures with multiple anti-seizure epileptic drugs, leading to serious outcomes. The pathogenesis of epilepsy is very complex and remains unclear. Brain-derived neurotrophic factor (BDNF), as a member of the neurotrophic factor family, is considered to play an important role in the survival, growth and differentiation of neurons during the development of the central nervous system. Recent years, a series of studies have reported that BDNF can maintain the function of the nervous system and promotes the regeneration of neurons after injury, which is believed to be closely related to epileptogenesis. However, two controversial views (BDNF inhibits or promotes epileptogenesis) still exist. Thus, this mini-review focuses on updating the new evidence of the role of BDNF in epileptogenesis and discussing the possibility of BDNF as an underlying target for the treatment of epilepsy.

Nerve Growth Factor Regulates the Expression of Brain-Derived Neurotrophic Factor mRNA in the Peripheral Nervous System

1996 ◽  
Vol 7 (2) ◽  
pp. 134-142 ◽  
Author(s):  
Stuart C. Apfel ◽  
Douglas E. Wright ◽  
Andrea M. Wiideman ◽  
Christine Dormia ◽  
William D. Snider ◽  
...  
Keyword(s):  
Nervous System ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Peripheral Nervous System ◽  
Neurotrophic Factor ◽  
Brain Derived Neurotrophic Factor ◽  
Nerve Growth
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