Evaluation of NDEL1 oligopeptidase activity in blood and brain in an animal model of schizophrenia: effects of psychostimulants and antipsychotics

Autor(es)

Nani, Joao V. ^{[1, 2, 3]} ; Lee, Richard S. ^[4] ; Yonamine, Camila M. ^{[1, 2]} ; Sant'Anna, Osvaldo A. ^[5] ; Juliano, Maria A. ^[6] ; Gadelha, Ary ^[3] ; Mari, Jair J. ^[3] ; Hayashi, Mirian A. F. ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] CNPq FAPESP CAPES, Natl Inst Translat Med INCT TM, Ribeirao Preto - Brazil

^[2] Univ Fed Sao Paulo UNIFESP, Dept Farmacol, Escola Paulista Med EPM, Rua 3 Maio 100, 3rd Floor, BR-04044020 Sao Paulo - Brazil

^[3] Univ Fed Sao Paulo UNIFESP, Dept Psychiat, Escola Paulista Med EPM, Sao Paulo - Brazil

^[4] Johns Hopkins Univ, Dept Psychiat & Behav Sci, Baltimore, MD - USA

^[5] Inst Butantan, Lab Immunochem, Sao Paulo - Brazil

^[6] Univ Fed Sao Paulo UNIFESP, Dept Biophys, Escola Paulista Med EPM, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: SCIENTIFIC REPORTS; v. 10, n. 1 OCT 28 2020.
• Citações Web of Science: 0

Resumo

Nuclear distribution element-like 1 (NDEL1) enzyme activity is important for neuritogenesis, neuronal migration, and neurodevelopment. We reported previously lower NDEL1 enzyme activity in blood of treated first episode psychosis and chronic schizophrenia (SCZ) compared to healthy control subjects, with even lower activity in treatment resistant chronic SCZ patients, implicating NDEL1 activity in SCZ. Herein, higher NDEL1 activity was observed in the blood and several brain regions of a validated animal model for SCZ at baseline. In addition, long-term treatment with typical or atypical antipsychotics, under conditions in which SCZ-like phenotypes were reported to be reversed in this animal model for SCZ, showed a significant NDEL1 activity reduction in blood and brain regions which is in line with clinical data. Importantly, these results support measuring NDEL1 enzyme activity in the peripheral blood to predict changes in NDEL1 activity in the CNS. Also, acute administration of psychostimulants, at levels reported to induce SCZ-like phenotype in normal rat strains, increased NDEL1 enzyme activity in blood. Therefore, alterations in NDEL1 activity after treatment with antipsychotics or psychostimulants may suggest a possible modulation of NDEL1 activity secondary to neurotransmission homeostasis and provide new insights into the role of NDEL1 in SCZ pathophysiology. (AU)

• Processo FAPESP: 19/09207-3 - Estudo do(s) mecanismo(s) molecular(es) e celular(es) em transtornos mentais
• Beneficiário: João Victor Silva Nani
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 17/02413-1 - Validação da crotamina como biomarcador e avaliação do seu potencial uso na terapia de doenças humanas
• Beneficiário: Mirian Akemi Furuie Hayashi
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 12/50191-4 - Síntese, estudo cinético e aplicações de substratos e inibidores de enzimas proteolíticas
• Beneficiário: Maria Aparecida Juliano
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 13/13392-4 - Avaliação do uso dos análogos da crotamina em diagnóstico ou terapia
• Beneficiário: Mirian Akemi Furuie Hayashi
• Modalidade de apoio: Auxílio à Pesquisa - Regular