Abstract
SummaryNeurotrophins are related to survival, growth, differentiation and neurotrophic maintenance as well as modulation of synaptic transmission in different regions of the nervous system. BDNF effects have been studied in the striatum due to the trophic role of BDNF in medium spiny neurons; however, less is known about the effects of NT‐4/5, which is also present in the striatum and activates the TrkB receptor along with BDNF. If both neurotrophins are present in the striatum, the following question arises: What role do they play in striatal physiology? Thus, the aim of this study was to determine the physiological effect of the sequential application and coexistence of BDNF and NT‐4/5 on the modulation of corticostriatal synapses. Our data demonstrated that neurotrophins exhibit differential effects depending on exposure order. BDNF did not modify NT‐4/5 effect; however, NT‐4/5 inhibited the effects of BDNF. Experiments carried out in COS‐7 cells to understand the mechanisms of this antagonism, indicated that NT‐4/5 exerts its inhibitory effect on BDNF by upregulating the TrkB.T1 and downregulating the TrkB‐FL isoforms of the TrkB receptor.
Highlights
Neurotrophins are growth factors with high homology in their se‐ quence and structure
The neurotrophins brain‐derived neurotrophic factor (BDNF) and neurotrophin‐4/5 (NT‐4/5) participate in synapse effi‐ cacy, and their final effects depend on the neuronal type, temporal timing of the physiological response and maturity of the experi‐ mental organism.[4,5,6,7]
TORRES‐CRUZ et al What is the purpose of the coexistence of two neurotrophins that ac‐ tivate the same tropomyosin receptor kinase (Trk) receptor in the same nucleus? Would TrkB sequen‐ tial stimulation result in the same physiological response? This study evaluates the physiological implications for corticostriatal synaptic transmission if either BDNF → NT‐4/5 or NT‐4/5 → BDNF responses take place
Summary
Neurotrophins are growth factors with high homology in their se‐ quence and structure. The neurotrophins brain‐derived neurotrophic factor (BDNF) and neurotrophin‐4/5 (NT‐4/5) participate in synapse effi‐ cacy, and their final effects depend on the neuronal type, temporal timing of the physiological response and maturity of the experi‐ mental organism.[4,5,6,7] In the neuromuscular plate, these neurotro‐ phins potentiate synaptic activity[8,9,10]; they modulate excitatory synaptic transmission in the nervous system through the activation of TrkB receptors.[9,11,12,13] TrkB receptors in turn trig‐ ger the MAPK, PI3K, and PLC‐γ signaling pathways in glutamatergic synapses.[14,15,16,17]
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