Peering into the mind: unraveling schizophrenia's secrets using models

Author(s)

Nani, Joao V. ; Muotri, Alysson R. ; Hayashi, Mirian A. F.

• Document type: Journal article
• Source: MOLECULAR PSYCHIATRY; v. N/A, p. 20-pg., 2024-09-08.

Abstract

Schizophrenia (SCZ) is a complex mental disorder characterized by a range of symptoms, including positive and negative symptoms, as well as cognitive impairments. Despite the extensive research, the underlying neurobiology of SCZ remain elusive. To overcome this challenge, the use of diverse laboratory modeling techniques, encompassing cellular and animal models, and innovative approaches like induced pluripotent stem cell (iPSC)-derived neuronal cultures or brain organoids and genetically engineered animal models, has been crucial. Immortalized cellular models provide controlled environments for investigating the molecular and neurochemical pathways involved in neuronal function, while iPSCs and brain organoids, derived from patient-specific sources, offer significant advantage in translational research by facilitating direct comparisons of cellular phenotypes between patient-derived neurons and healthy-control neurons. Animal models can recapitulate the different psychopathological aspects that should be modeled, offering valuable insights into the neurobiology of SCZ. In addition, invertebrates' models are genetically tractable and offer a powerful approach to dissect the core genetic underpinnings of SCZ, while vertebrate models, especially mammals, with their more complex nervous systems and behavioral repertoire, provide a closer approximation of the human condition to study SCZ-related traits. This narrative review provides a comprehensive overview of the diverse modeling approaches, critically evaluating their strengths and limitations. By synthesizing knowledge from these models, this review offers a valuable source for researchers, clinicians, and stakeholders alike. Integrating findings across these different models may allow us to build a more holistic picture of SCZ pathophysiology, facilitating the exploration of new research avenues and informed decision-making for interventions. (AU)

• FAPESP's process: 19/09207-3 - Study of molecular and cellular mechanisms in mental disorders
• Grantee: João Victor Silva Nani
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 20/01107-7 - Study to optimize the use of crotamine as a theranostic in the therapy of human diseases: cancer, metabolic syndrome and renal dysfunction
• Grantee: Mirian Akemi Furuie Hayashi
• Support Opportunities: Regular Research Grants
• FAPESP's process: 22/00527-8 - Enzymatic activity of oligopeptidases Ndel1 and/or ACE in plasma or blood serum of patients with Depression
• Grantee: Larissa Ribino Parra
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 17/02413-1 - Validation of crotamine as a biomarker and evaluation of its potential use in the therapy of human diseases
• Grantee: Mirian Akemi Furuie Hayashi
• Support Opportunities: Regular Research Grants
• FAPESP's process: 19/08287-3 - Effect of crotamine on glucose uptake by brown adipose tissue: evaluation in an experimental model with 18FDG PET
• Grantee: Marcelo Tatit Sapienza
• Support Opportunities: Regular Research Grants
• FAPESP's process: 22/03297-3 - Exploring the molecular and cellular mechanism(s) underlying neurodevelopmental disorders: investigating the role(s) of Nuclear Distribution Element like-1 (Ndel1)
• Grantee: João Victor Silva Nani
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 19/13112-8 - Study of molecular and cellular mechanisms involved in mental disorders: clinical and animal models analysis
• Grantee: Mirian Akemi Furuie Hayashi
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 14/50891-1 - INCT 2014: Translational Medicine
• Grantee: Jaime Eduardo Cecilio Hallak
• Support Opportunities: Research Projects - Thematic Grants