Testosterone modulates respiratory control but does not exert neuroprotective effects in a Parkinson's disease model

Autor(es)

Aquino, Yasmin C. ; Pedrao, Luiz F. ; Moreira, Thiago S. ; Falquetto, Barbara ; Takakura, Ana C.

• Tipo de documento: Artigo Científico
• Fonte: Brain Research; v. 1864, p. 11-pg., 2025-07-11.

Resumo

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra (SN). Patients with PD exhibit classic motor symptoms such as tremors and bradykinesia, as well as non-classical symptoms, including respiratory dysfunctions, which significantly contribute to increased mortality. Epidemiological studies suggest that men are more frequently affected by PD, although the role of testosterone remains unclear. Therefore, this study aimed to investigate the role of testosterone in modulating respiratory activity and respiratory nuclei under basal conditions and in an experimental PD model. Testosterone was directly administered into the fourth brain ventricle (4 V) of C57BL/6 mice, while a separate group underwent orchiectomy (ORX) followed by induction of the experimental PD model. Both functional and neuroanatomical aspects of respiratory activity were evaluated. Testosterone injection into the 4 V reduced basal respiratory frequency, both acutely and subchronically. ORX animals showed a modest (similar to 12 %) reduction in TH+ neurons in the SN under basal conditions. However, both PD groups (Sham and ORX) exhibited a similar and extensive neuronal loss (similar to 76 %). Changes in basal respiratory activity, as well as in the density of neurokinin-1 receptors and phox2b(+) neurons in the medullary respiratory nuclei, were detected exclusively in the PD model, with no significant differences in the control or ORX groups. These findings suggest that while testosterone modulates basal respiratory activity and may have a modest effect on dopaminergic neurons maintenance under physiological conditions its reduction through ORX does not influence neurodegeneration or respiratory dysfunction observed in the PD model. (AU)

• Processo FAPESP: 20/16320-8 - Investigação da existência de projeções anatômicas da substância negra para o complexo pré-Bötzinger
• Beneficiário: Yasmin Cestari Aquino
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 21/05299-0 - Controle do ritmo e da quimiossensibilidade respiratória pelo tronco encefálico: aspectos moleculares, celulares, fisiológicos e patológicos
• Beneficiário: Thiago dos Santos Moreira
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 23/00980-7 - Caracterização epigenética nos núcleos respiratórios no modelo animal 6-OHDA da doença de Parkinson
• Beneficiário: Bárbara Falquetto
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 21/09768-5 - Influências do dimorfismo sexual, inflamação e sono nas alterações respiratórias observadas na Doença de Parkinson
• Beneficiário: Ana Carolina Takakura Moreira
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 23/11274-6 - A ação da via inflamatória dependente de GSK3b e JAK/STAT nos núcleos respiratórios no modelo de Doença de Parkinson em camundongos após tratamento com minociclina.
• Beneficiário: Luiz Fernando de Araujo Trindade Pedrao
• Modalidade de apoio: Bolsas no Brasil - Doutorado