Clozapine response and crosstalk between astrocytes and adipocytes

  • Author
  • Júlia de Moraes Crisostomo
  • Co-authors
  • Adriana Santoro , Daniel Martins-de-Souza
  • Abstract
  •  

    Schizophrenia is an incurable and chronic psychiatric disorder managed with antipsychotics, although their complex cellular mechanisms remain incompletely understood. Clozapine, considered one of the most effective antipsychotics, can cause side effects such as metabolic syndrome, which is responsible for increasing the rate of medication dropout. Metabolites secreted by adipocytes during metabolic syndrome regulate physiological responses, including those in astrocytes, which are important glial cells for maintaining the central nervous system's health. One enzyme that regulates astrocyte functions is the membrane protein Na/K-ATPase, which controls the ionic gradient and participates in cell signaling pathways. Given all these, this study aims to investigate the astrocyte response to adipocyte metabolites secreted during clozapine treatment. For this purpose, human preadipocytes were differentiated into white adipocytes, both treated with clozapine. Their conditioned medium was then collected. Human neural stem cell-derived astrocytes were cultured in adipocytes-conditioned medium. Subsequent analyses were performed by RT-qPCR (IL-6, TGF-?1, and TNF?), lipidomics, and proteomics. A concentration of 50 µM clozapine has been established for treating human preadipocytes and white adipocytes. Astrocytes exposed to clozapine-treated adipocyte-conditioned medium showed modulation of proteins involved in RNA processing, the ubiquitin-proteasome pathway, and glutamatergic transport, including Na/K-ATPase and glutamate transporters. In contrast, astrocytes treated with preadipocytes-conditioned medium only modulated proteins related to cell organization. Both adipocytes-conditioned media, in astrocytes tended to increase gene expression of IL-6, TGF-?1, and TNF? cytokines and modulated the secretion of lipids related to glutamatergic uptake, apoptosis, and pro-inflammatory pathways. According to these results, white adipocyte metabolism potentially modulates glutamate uptake via Na/K-ATPase, suggesting a modulation in astrocytes under the influence of clozapine-treated white adipocyte-conditioned medium. These findings are expected to contribute to a better understanding of the correlation between adipocytes, astrocytes, and clozapine, highlighting the potential mechanisms underlying changes in adipocyte metabolism and its association with astrocytes.

  • Keywords
  • Schizophrenia, Sodium Pump, Astrocytes
  • Subject Area
  • Na Pump
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Dear Colleagues and Friends,

We are thrilled to extend a warm welcome to the 8th Annual Meeting of the Cardiotonic Steroids and Na Pump, in collaboration with the Brazilian Society of Pharmacology and Experimental Therapeutic Society (SBFTE) and the Brazilian Society for Biochemistry and Molecular Biology (SBBq). The event is scheduled to take place at the Federal University of São João del Rei (UFSJ) from August 20th to 23rd, 2024.

The Na pump meeting stands as one of Brazil's most enduring scientific gatherings. Over the past decade, it has been hosted by various Brazilian institutions, serving as a pivotal platform for scientific discussions that contribute significantly to the advancement of fundamental knowledge in Na, K-ATPase biochemistry, molecular biology, and related fields. Additionally, it serves as a forum for dialogues on scientific education and training, generating consensus that can influence public policies for the betterment of society.

For this year's meeting, the organizing committee has curated an engaging interdisciplinary program, featuring lectures by esteemed foreign scientists. These sessions will delve into the latest advancements and current challenges across a broad spectrum of research topics in Biochemistry and the Molecular Na pump signaling cascade.

We eagerly anticipate your participation in this exciting scientific event and hope to see you soon in Minas Gerais!

Best regards,

Scientific Committee

Comissão Organizadora

Dr Leandro Augusto Barbosa

Dr Vanessa Faria Cortes

Sílvia Ramos Silva 
Marina Vieira

Anna Karolina de Oliveira Alfenas Gadelha - Mídias Sociais e Papelaria
Jessica Alves Faria -  Coffee Break e Gráfica
Lucas Antônio Lisboa Ribeiro - Apresentação/Cerimonial
Poliana Amorim Santos - Abertura/ Encerramento/ parte recreativa
?Ana Gabriela Finamore dos Santo-Midias Sociais e Suporte Técnico.
Thiago Malverde de Oliveira - Divulgação (SJDR) e suporte

Maurício Gustavo Oliveira - Credenciamento
Ítalo Leonardo Diogo - Contato com a pós-graduação e Controle de Frequência
Julia Lopes Granato - Midias sociais e controle de frequência

 

Comissão Científica

Dr. Gustavo Blanco – Kansas University Medical Center, USA

Dr. John Hamlyn – University of Maryland, USA

Dr. Rúben Gerardo Contreras Patiño – CINVESTAV, Mexico

Dra. Vanessa Faria Cortes - Federal University of São João del-Rei, Brazil

Dr Carlos Frederico Leite Fontes - Federal University of Rio de Janeiro, Brazil

Dr Cristoforo Scavone - University of Sao Paulo

 

 

 

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