title: Brain derived neurotrophic factor and neurotrophin-4 employ different intracellular pathways to modulate norepinephrine uptake and release in rat hypothalamus.
abstract: Classical actions of the neurotrophin family are related to cellular survival and differentiation. Moreover, acute effects of neurotrophins have been reported. Although neurotrophins effects on synaptic transmission at central nervous system level have been largely studied, acute effects of neurotrophins on hypothalamic noradrenergic transmission are still poorly understood. Thus, we have studied the effects of the neurotrophin family members nerve growth factor (NGF), brain derived neurotrophic factor (BDNF) and neurotrophin-4 (NT-4) on norepinephrine (NE) neuronal uptake and its evoked release, as well as the receptor and the intracellular pathways involved in these processes in rat hypothalamus. Present results indicate that BDNF increased NE uptake and decreased its evoked release through a mechanism that involve Trk B receptor and phospholipase C. Moreover, NT-4, also through the Trk B receptor, decreased NE uptake and its evoked release by activating phosphatidylinositol 3-OH-kinase. These effects were observed in whole hypothalamus as well as in the anterior hypothalamic zone. On the other hand, NGF did not modify noradrenergic transmission. In conclusion, we showed for the first time that BDNF and NT-4 activate two different intracellular signalling pathways through a Trk B receptor dependent mechanism. Furthermore, present findings support the hypothesis that BDNF and NT-4 acutely applied, could be considered as modulators of noradrenergic transmission and thus may regulate hypothalamic physiological as well as pathophysiological responses.
authors: Cátedra de Fisiopatología, Facultad de Farmacia y Bioquímica, INFIBIOC, Universidad de Buenos Aires, CONICET, C1113AAD Buenos Aires, Argentina. martinrf@ffyb.uba.ar
authors: M
authors: M
authors: Rodríguez Fermepin
authors: M
authors: M
authors: Trinchero
authors: J
authors: J
authors: Minetto
authors: A
authors: A
authors: Beltrán
authors: B E
authors: BE
authors: Fernández
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000378:metabolism*; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000378:metabolism; D005260:Female; D007031:Hypothalamus / Q000033:anatomy & histology / Q000378:metabolism*; D008297:Male; D020932:Nerve Growth Factor / Q000378:metabolism; D009414:Nerve Growth Factors / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000316:Adrenergic alpha-Agonists; D019208:Brain-Derived Neurotrophic Factor; D004791:Enzyme Inhibitors; D020932:Nerve Growth Factor; D009414:Nerve Growth Factors; D009638:Norepinephrine; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D020813:Receptor, trkB; D010738:Type C Phospholipases; C073922:neurotrophin 4