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

Authors

  • Renata L. Fleming,

    1. Laboratório de Neuroquímica, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, RJ, Brazil
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    • These authors contributed equally to this study.
  • Mariana S. Silveira,

    1. Laboratório de Neurogênese, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, RJ, Brazil
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    • These authors contributed equally to this study.
  • Luís E. Santos,

    1. Laboratório de Neuroquímica, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, RJ, Brazil
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  • Isabela P. Henze,

    1. Laboratório de Neuroquímica, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, RJ, Brazil
    Current affiliation:
    1. Centro Universitário, Celso Lisboa, Brazil
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  • Patrícia F. Gardino,

    1. Laboratório de Neurobiologia da Retina, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, RJ, Brazil
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  • Maria Christina F. de Mello,

    1. Laboratório de Neuroquímica, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, RJ, Brazil
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  • Fernando G. de Mello

    Corresponding author
    • Laboratório de Neuroquímica, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, RJ, Brazil
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Address correspondence and reprint requests to Fernando G. de Mello, Instituto de Biofisica Carlos Chagas Filho – UFRJ, Av. Carlos Chagas Filho, 373, Edifício do Centro de Ciencias da Saude, Bloco G, Cidade Universitaria, Ilha do Fundão, 21941-902, Rio de Janeiro, Brazil. E-mail: fgmello@biof.ufrj.br.

Abstract

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.

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