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Brain metabolic and behavioral alterations in a Down syndrome model

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Souza, Larissa Estessi de ; Righini, Chiara Maria ; Mantovani, Dimitri Brigide de Almeida ; Silva, Manuella Penido ; Lazzarotto, Gabriela ; Limberger, Christian ; Buchpiguel, Carlos Alberto ; Zimmer, Eduardo Rigon ; Real, Caroline Cristiano ; Spelta, Lidia Emmanuela Wiazowski ; Faria, Daniele de Paula
Número total de Autores: 11
Tipo de documento: Artigo Científico
Fonte: NUCLEAR MEDICINE AND BIOLOGY; v. 148, p. 15-pg., 2025-09-01.
Resumo

Purpose: This work aimed to monitor the Down Syndrome Ts65Dn animal model across lifespan to detect timedependent in vivo molecular alterations that may be associated with neurodegeneration and neuroinflammation in this model. Methods: Euploid and trisomic Ts65Dn animals were longitudinally evaluated at 2, 5, 14, 20, and 24 months of age using brain [18F]FDG PET and behavioral tasks (open field and novel object recognition). VOI-based SUV, Voxel-wise, and metabolic network analyses were performed. Cross-sectional post-mortem brain analysis was carried out at the same ages to measure neuronal loss and microglia activation. Results: There was an increase in brain metabolism at 14 months of age in both genotypes, when compared to the other analyzed ages. [18F]FDG uptake correlated with microglia activation measured by Iba-1 immunohistochemistry, suggesting that the tracer increased due to a neuroinflammation process. In addition, metabolic network analysis showed more accentuated desynchronization in [18F]FDG uptake in older trisomic mice, than in euploid animals. At 24 months of age, trisomic animals presented a worse long-term memory recognition index and an age-dependent decrease in NeuN staining, which was not associated with [18F]FDG uptake. Conclusions: This is the first study to monitor the Ts65Dn mouse model throughout life - from 2 to 24 months of age - using [18F]FDG PET imaging and metabolic network analysis. Our results collectively highlight that trisomic mice experience early disruption in brain network organization, likely contributing to functional impairments associated with aging, neurodegeneration, and neuroinflammation. (AU)

Processo FAPESP: 24/14294-0 - Avaliação de Processos Moleculares Cerebrais no Envelhecimento Humano a partir de Imagens Dinâmicas de Tomografia por Emissão de Pósitrons
Beneficiário:Dimitri Brigide de Almeida Mantovani
Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
Processo FAPESP: 19/15654-2 - Avaliação de alterações moleculares associadas ao envelhecimento em modelo de Síndrome de Down
Beneficiário:Larissa Estessi de Souza
Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
Processo FAPESP: 18/15167-1 - Neuroimagem translacional na deficiência intelectual: avaliação de alterações moleculares associadas ao envelhecimento na Síndrome de Down
Beneficiário:Daniele de Paula Faria
Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
Processo FAPESP: 22/06370-3 - Avaliação do efeito do canabidiol no processo de envelhecimento de modelo transgênico de síndrome de Down
Beneficiário:Lidia Emmanuela Wiazowski Spelta
Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
Processo FAPESP: 20/08015-0 - Avaliação comportamental e histológica de modelo animal de Síndrome de Down
Beneficiário:Manuella Penido Silva
Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
Processo FAPESP: 23/15682-1 - Avaliação do efeito sinérgico do tratamento com canabidiol e exercício físico no modelo transgênico de Síndrome de Down, Ts65Dn.
Beneficiário:Chiara Maria Righini
Modalidade de apoio: Bolsas no Brasil - Iniciação Científica