Cell-based therapies for the treatment of schizophrenia

Donegan, Jennifer J.; Lodge, Daniel J.

doi:10.1016/j.brainres.2016.08.010

Cited by 14 publications

(12 citation statements)

References 112 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…People with SZ have reduced stem cell proliferation in the dentate gyrus. Next, SZ patients demonstrate a reduced number of synapses between the hippocampal mossy fibers and pyramidal neurons, which is associated with changes in synaptic plasticity markers [17,18]. All above findings confirm the dysfunction of the hippocampus structure in SZ.…”

Section: Neuroanatomy Of Szsupporting

confidence: 63%

See 1 more Smart Citation

In Vitro and In Vivo Models for the Investigation of Potential Drugs Against Schizophrenia

et al. 2020

View full text Add to dashboard Cite

Schizophrenia (SZ) is a complex psychiatric disorder characterized by positive, negative, and cognitive symptoms, and is not satisfactorily treated by current antipsychotics. Progress in understanding the basic pathomechanism of the disease has been hampered by the lack of appropriate models. In order to develop modern drugs against SZ, efficient methods to study them in in vitro and in vivo models of this disease are required. In this review a short presentation of current hypotheses and concepts of SZ is followed by a description of current progress in the field of SZ experimental models. A critical discussion of advantages and limitations of in vitro models and pharmacological, genetic, and neurodevelopmental in vivo models for positive, negative, and cognitive symptoms of the disease is provided. In particular, this review concerns the important issue of how cellular and animal systems can help to meet the challenges of modeling the disease, which fully manifests only in humans, as experimental studies of SZ in humans are limited. Next, it is emphasized that novel clinical candidates should be evaluated in animal models for treatment-resistant SZ. In conclusion, the plurality of available in vitro and in vivo models is a consequence of the complex nature of SZ, and there are extensive possibilities for their integration. Future development of more efficient antipsychotics reflecting the pleiotropy of symptoms in SZ requires the incorporation of various models into one uniting model of the multifactorial disorder and use of this model for the evaluation of new drugs.

show abstract

Section: Neuroanatomy Of Szsupporting

confidence: 63%

“…Therefore, it is considered that abnormal prefrontal cortex activity contributes to cognitive dysfunction observed in patients with SZ. Interestingly, the prefrontal cortex and hippocampus are connected neuronal systems and dysregulated prefrontal and hippocampal activity may underlie some of the symptoms of SZ [18].…”

Section: Neuroanatomy Of Szmentioning

confidence: 99%

In Vitro and In Vivo Models for the Investigation of Potential Drugs Against Schizophrenia

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Recently, these limitations have been addressed by advances in the xenotransplantation of cells and organoids differentiated from human PSCs. Given the recent explosion of cell-based therapies under investigation in the preclinical or clinical settings for many diseases [96][97][98][99][100] , iPSC-based chimaeric disease modelling by xenotransplantation has emerged as a reliable tool to fuel these advances by faithfully modelling human disease (Fig. 3, Box 1).…”

Section: Human-animal Chimaerasmentioning

confidence: 99%

Induced pluripotent stem cells in disease modelling and drug discovery

2019

View full text Add to dashboard Cite

The derivation of induced pluripotent stem cells (iPSCs) over a decade ago sparked widespread enthusiasm for the development of new models of human disease, enhanced platforms for drug discovery, and more widespread use of autologous cell-based therapy. Early studies using directed differentiation of iPSCs frequently uncovered cell-level phenotypes in monogenic diseases, but translation to tissue-level and organ-level diseases has required development of more complex, 3D, multicellular systems. Organoids and human-rodent chimaeras more accurately mirror the diverse cellular ecosystems of complex tissues and are being applied to iPSC disease models to recapitulate the pathobiology of a broad spectrum of human maladies, including infectious diseases, genetic disorders and cancer.

show abstract

“…These findings may be significant as interneuron dysfunction has been associated with a variety of neurodevelopmental and psychiatric disorders, including schizophrenia, autism, and intellectual disability (37). For example, schizophrenia patients have decreased expression of the GABA synthesizing enzyme, glutamic acid decarboxylase (GAD), in the prefrontal cortex, an effect that seems to reflect not a loss of cells but rather a loss of function in specific subclasses of interneurons (38). We have recently demonstrated that disrupting interneuron function in the cortex can produce schizophrenia-like deficits in social interaction and cognitive function in otherwise healthy animals (39).…”

Section: Prenatal Buprenorphine Exposure Alters Interneuron Migrationmentioning

confidence: 99%

Buprenorphine exposure alters the development and migration of interneurons in the cortex

Nieto‐Estévez

Donegan

McMahon

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

The misuse of opioids has reached epidemic proportions over the last decade, with over 2.1 million people in the U.S. suffering from substance use disorders related to prescription opioid pain relievers. This increase in opioid misuse affects all demographics of society, including women of child-bearing age, which has led to a rise in opioid use during pregnancy. Opioid use during pregnancy has been associated with increased risk of obstetric complications and adverse neonatal outcomes, including neonatal abstinence syndrome. Currently, opioid use disorder in pregnant women is treated with long-acting opioid agonists, including buprenorphine. Although buprenorphine reduces illicit opioid use during pregnancy and improves infant outcomes at birth, few long-term studies of the neurodevelopmental consequences have been conducted. The goal of the current experiments was to examine the effects of buprenorphine on the development of the cortex using fetal brain tissue, 3D brain cultures, and rodent models. First, we demonstrated that we can grow cortical and subpallial spheroids, which model the cellular diversity, connectivity, and activity of the developing human brain. Next, we show that cells in the developing human cortex express the nociceptin opioid (NOP) receptor and that buprenorphine can signal through this receptor in cortical spheroids. Using subpallial spheroids to grow inhibitory interneurons, we show that buprenorphine can alter interneuron development and migration into the cortex. Finally, using a rodent model of prenatal buprenorphine exposure, we demonstrate that alterations in interneuron distribution can persist into adulthood. Together, these results suggest that more research is needed into the long-lasting consequences of buprenorphine exposure on the developing human brain.

show abstract

Cell-based therapies for the treatment of schizophrenia

Cited by 14 publications

References 112 publications

In Vitro and In Vivo Models for the Investigation of Potential Drugs Against Schizophrenia

In Vitro and In Vivo Models for the Investigation of Potential Drugs Against Schizophrenia

Induced pluripotent stem cells in disease modelling and drug discovery

Buprenorphine exposure alters the development and migration of interneurons in the cortex

Contact Info

Product

Resources

About