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Using iPSC Models to Understand the Role of Estrogen in Neuron–Glia Interactions in Schizophrenia and Bipolar Disorder

1
NORMENT, Institute of Clinical Medicine, University of Oslo & Division of Mental Health and Addiction, Oslo University Hospital, 0450 Oslo, Norway
2
Department of Medical Genetics, Oslo University Hospital, 0450 Oslo, Norway
3
Department of Neurosciences, University of California San Diego, La Jolla, CA 92093, USA
4
Division of Mental Health and Addiction, Oslo University Hospital, 0372 Oslo, Norway
5
NORMENT, Department of Clinical Science, University of Bergen, 5020 Bergen, Norway
*
Authors to whom correspondence should be addressed.
Cells 2021, 10(2), 209; https://doi.org/10.3390/cells10020209
Received: 14 November 2020 / Revised: 8 December 2020 / Accepted: 19 January 2021 / Published: 21 January 2021
(This article belongs to the Special Issue Neuron-Glia Interactions)
Schizophrenia (SCZ) and bipolar disorder (BIP) are severe mental disorders with a considerable disease burden worldwide due to early age of onset, chronicity, and lack of efficient treatments or prevention strategies. Whilst our current knowledge is that SCZ and BIP are highly heritable and share common pathophysiological mechanisms associated with cellular signaling, neurotransmission, energy metabolism, and neuroinflammation, the development of novel therapies has been hampered by the unavailability of appropriate models to identify novel targetable pathomechanisms. Recent data suggest that neuron–glia interactions are disturbed in SCZ and BIP, and are modulated by estrogen (E2). However, most of the knowledge we have so far on the neuromodulatory effects of E2 came from studies on animal models and human cell lines, and may not accurately reflect many processes occurring exclusively in the human brain. Thus, here we highlight the advantages of using induced pluripotent stem cell (iPSC) models to revisit studies of mechanisms underlying beneficial effects of E2 in human brain cells. A better understanding of these mechanisms opens the opportunity to identify putative targets of novel therapeutic agents for SCZ and BIP. In this review, we first summarize the literature on the molecular mechanisms involved in SCZ and BIP pathology and the beneficial effects of E2 on neuron–glia interactions. Then, we briefly present the most recent developments in the iPSC field, emphasizing the potential of using patient-derived iPSCs as more relevant models to study the effects of E2 on neuron–glia interactions. View Full-Text
Keywords: schizophrenia; bipolar disorder; estrogen; neuron–glia interactions; iPS cells; brain organoids; drug target; pathophysiological mechanisms; in vitro model schizophrenia; bipolar disorder; estrogen; neuron–glia interactions; iPS cells; brain organoids; drug target; pathophysiological mechanisms; in vitro model
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MDPI and ACS Style

Reis de Assis, D.; Szabo, A.; Requena Osete, J.; Puppo, F.; O’Connell, K.S.; A. Akkouh, I.; Hughes, T.; Frei, E.; A. Andreassen, O.; Djurovic, S. Using iPSC Models to Understand the Role of Estrogen in Neuron–Glia Interactions in Schizophrenia and Bipolar Disorder. Cells 2021, 10, 209. https://doi.org/10.3390/cells10020209

AMA Style

Reis de Assis D, Szabo A, Requena Osete J, Puppo F, O’Connell KS, A. Akkouh I, Hughes T, Frei E, A. Andreassen O, Djurovic S. Using iPSC Models to Understand the Role of Estrogen in Neuron–Glia Interactions in Schizophrenia and Bipolar Disorder. Cells. 2021; 10(2):209. https://doi.org/10.3390/cells10020209

Chicago/Turabian Style

Reis de Assis, Denis; Szabo, Attila; Requena Osete, Jordi; Puppo, Francesca; O’Connell, Kevin S.; A. Akkouh, Ibrahim; Hughes, Timothy; Frei, Evgeniia; A. Andreassen, Ole; Djurovic, Srdjan. 2021. "Using iPSC Models to Understand the Role of Estrogen in Neuron–Glia Interactions in Schizophrenia and Bipolar Disorder" Cells 10, no. 2: 209. https://doi.org/10.3390/cells10020209

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