In Vitro Recapitulation of Neuropsychiatric Disorders with Pluripotent Stem Cells-Derived Brain Organoids

Gulimiheranmu, Maisumu; Li, Shuang; Zhou, Junmei

doi:10.3390/ijerph182312431

Cited by 8 publications

(3 citation statements)

References 87 publications

(155 reference statements)

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“…Human brain organoids recapitulate the tissue architecture of the developing cortex to a remarkable degree of fidelity, even discriminating species differences in the development dynamics of neurons between humans and gorilla [ 19 ]. Since the initial nearly parallel work by three research groups [ 20 , 21 , 22 ], brain organoids have served in modelling various brain diseases [ 23 , 24 , 25 , 26 ], including microcephaly [ 20 ], glioblastoma [ 27 , 28 , 29 ], Zika-virus infection [ 30 ] and Alzheimer’s disease [ 31 , 32 , 33 ].…”

Section: Introductionmentioning

confidence: 99%

Microglia-like Cells Promote Neuronal Functions in Cerebral Organoids

Fagerlund

Dougalis

Shakirzyanova

et al. 2021

Cells

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Human cerebral organoids, derived from induced pluripotent stem cells, offer a unique in vitro research window to the development of the cerebral cortex. However, a key player in the developing brain, the microglia, do not natively emerge in cerebral organoids. Here we show that erythromyeloid progenitors (EMPs), differentiated from induced pluripotent stem cells, migrate to cerebral organoids, and mature into microglia-like cells and interact with synaptic material. Patch-clamp electrophysiological recordings show that the microglia-like population supported the emergence of more mature and diversified neuronal phenotypes displaying repetitive firing of action potentials, low-threshold spikes and synaptic activity, while multielectrode array recordings revealed spontaneous bursting activity and increased power of gamma-band oscillations upon pharmacological challenge with NMDA. To conclude, microglia-like cells within the organoids promote neuronal and network maturation and recapitulate some aspects of microglia-neuron co-development in vivo, indicating that cerebral organoids could be a useful biorealistic human in vitro platform for studying microglia-neuron interactions.

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Section: Introductionmentioning

confidence: 99%

Microglia-like Cells Promote Neuronal Functions in Cerebral Organoids

Fagerlund

Dougalis

Shakirzyanova

et al. 2021

Cells

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“…Furthermore, several pathological characteristics of neuropsychiatric disorders were recapitulated using human brain organoids [207]. For example, genetically modified iPSC brain organoids carrying mutations in CHD8 (chromodomain helicase DNA-binding protein 8), one of the most commonly mutated genes in patients with autism spectrum disorder (ASD), bipolar disorder (BPI), schizophrenia and intellectual disabilities, were generated [208,209].…”

Section: Organoid Modelsmentioning

confidence: 99%

Polyphenols in Inner Ear Neurobiology, Health and Disease: From Bench to Clinics

Osakabe,

Modafferi,

Ontario

et al. 2023

Medicina

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There is substantial experimental and clinical interest in providing effective ways to both prevent and slow the onset of hearing loss. Auditory hair cells, which occur along the basilar membrane of the cochlea, often lose functionality due to age-related biological alterations, as well as from exposure to high decibel sounds affecting a diminished/damaged auditory sensitivity. Hearing loss is also seen to take place due to neuronal degeneration before or following hair cell destruction/loss. A strategy is necessary to protect hair cells and XIII cranial/auditory nerve cells prior to injury and throughout aging. Within this context, it was proposed that cochlea neural stem cells may be protected from such aging and environmental/noise insults via the ingestion of protective dietary supplements. Of particular importance is that these studies typically display a hormetic-like biphasic dose–response pattern that prevents the occurrence of auditory cell damage induced by various model chemical toxins, such as cisplatin. Likewise, the hormetic dose–response also enhances the occurrence of cochlear neural cell viability, proliferation, and differentiation. These findings are particularly important since they confirmed a strong dose dependency of the significant beneficial effects (which is biphasic), whilst having a low-dose beneficial response, whereas extensive exposures may become ineffective and/or potentially harmful. According to hormesis, phytochemicals including polyphenols exhibit biphasic dose–response effects activating low-dose antioxidant signaling pathways, resulting in the upregulation of vitagenes, a group of genes involved in preserving cellular homeostasis during stressful conditions. Modulation of the vitagene network through polyphenols increases cellular resilience mechanisms, thus impacting neurological disorder pathophysiology. Here, we aimed to explore polyphenols targeting the NF-E2-related factor 2 (Nrf2) pathway to neuroprotective and therapeutic strategies that can potentially reduce oxidative stress and inflammation, thus preventing auditory hair cell and XIII cranial/auditory nerve cell degeneration. Furthermore, we explored techniques to enhance their bioavailability and efficacy.

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“…This included two cross-sectional studies: one of ocular changes in adolescents with diabetes mellitus in health facilities in Ghana [25], and one on the association of salivary insulin-like growth factor (IGF) and IGF/IGFBP-3 molar ratios with cervical vertebral maturation stages from pre-adolescent to post-adolescent transition period [26]. Furthermore, a review of factors influencing abnormal brain development focused on neuropsychiatric disorders with pluripotent stem cells-derived brain organoids [27].…”

Section: Food Nutrition Biological and Molecular Aspectsmentioning

confidence: 99%