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Pituitary adenylyl cyclase‐activating polypeptide receptor re‐sensitization induces plastic changes in the dopaminergic phenotype in the mature avian retina

Fleming, Renata L. ; Silveira, Mariana S. ; Santos, Luís E. ; Henze, Isabela P. ; Gardino, Patrícia F. ; Mello, Maria Christina F. ; Mello, Fernando G.

Journal of neurochemistry, 2013-03, Vol.124 (5), p.621-631 [Periódico revisado por pares]

England: Blackwell Publishing Ltd

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  • Título:
    Pituitary adenylyl cyclase‐activating polypeptide receptor re‐sensitization induces plastic changes in the dopaminergic phenotype in the mature avian retina
  • Autor: Fleming, Renata L. ; Silveira, Mariana S. ; Santos, Luís E. ; Henze, Isabela P. ; Gardino, Patrícia F. ; Mello, Maria Christina F. ; Mello, Fernando G.
  • Assuntos: Adenylate cyclase ; Animals ; Blotting, Western ; cAMP ; Chickens ; Cyclic AMP ; desensitization ; Dopamine ; dopaminergic neurons ; Immunohistochemistry ; Neuronal Plasticity - physiology ; NURR1 ; Phenotype ; phenotypic plasticity ; Pituitary Adenylate Cyclase-Activating Polypeptide - metabolism ; Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide - metabolism ; Retina - metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; tyrosine hydroxylase
  • É parte de: Journal of neurochemistry, 2013-03, Vol.124 (5), p.621-631
  • Notas: ObjectType-Article-1
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  • Descrição: Pituitary Adenylyl Cyclase‐Activating Polypeptide (PACAP) is a neuroactive peptide present in the avian retina where it activates adenylyl cyclase (AC) since early in development via PACAP receptors. The synthesis of cAMP in response to PACAP is observed since embryonic day 8/9 (E8/9). After E12, signaling via PACAP receptors desensitizes, reaching very low levels in the mature tissue. We show here that chronic administration of PACAP in vitro desensitizes PACAP‐induced cAMP accumulation, while the administration of the PACAP antagonist (PACAP 6‐38) re‐sensitizes PACAP receptor/cyclase system in vitro and in vivo. Moreover, a twofold increase in the number of tyrosine hydroxylase positive (TH+) cells is observed after in vivo injection of PACAP6‐38. NURR1, a transcription factor associated with the differentiation of dopaminergic cells in the CNS, is present in the chick retina in all developmental stages studied. The presence of NURR1 positive cells in the mature tissue far exceeds the number of TH+ cells, suggesting that these NURR1‐positive cells might have the potential to express the dopaminergic phenotype. Our data show that if PACAP signaling is increased in mature retinas, plastic changes in dopaminergic phenotype can be achieved. PACAP is a neuroactive peptide which activates adenylyl cyclase in the retina. Chronic administration of PACAP in vitro desensitizes its response, while the PACAP receptor antagonist re‐sensitizes the PACAP system in vitro and in vivo. NURR1 is a transcription factor associated with the dopaminergic phenotype and in embryonic and mature retinas the number of cells expressing NURR1 far exceeds the number of Tyrosine Hydroxylase positive cells. Injection (in vivo) of PACAP antagonist induces a twofold increase in the number of these cells and an increased network of their neurites. Our data show that, increased PACAP signaling in mature retinas induces plastic changes in dopaminergic phenotype.
  • Editor: England: Blackwell Publishing Ltd
  • Idioma: Inglês
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  • Realização: ABCD-USP USP   Logos de Redes Sociais: Freepik

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