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Stroke is the leading cause of death and long-term disability worldwide. But treatments are not available to promote functional recovery, and efficient therapies need to be investigated. Stem cell-based therapies hold great promise as potential technologies to restore function in brain disorders. Loss of GABAergic interneurons after stroke may result in sensorimotor defects. Here, by transplanting human brain organoids resembling the MGE domain (human MGE organoids, hMGEOs) derived from human induced pluripotent stem cells (hiPSCs) into the infarcted cortex of stroke mice, we found that grafted hMGEOs survived well and primarily differentiated into GABAergic interneurons and significantly restored the sensorimotor deficits of stroke mice for a long time. Our study offers the feasibility of stem cell replacement therapeutics strategy for stroke.
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http://dx.doi.org/10.1016/j.bbrc.2023.06.010 | DOI Listing |
Mol Psychiatry
September 2025
Department of Pharmacology, School of Basic Medicine and Department of Pharmacy, Tongji Hospital, Tongji Medical College; and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China. chenjg@hu
Dysfunction of parvalbumin-expressing interneurons (PV-INs) in the cerebral cortex has been implicated in major depressive disorder. Perineuronal nets (PNNs), which encapsulate PV-INs, are considered to influence the structural and functional properties of PV-INs. Semaphorin 3A (Sema3A) is a secreted protein constituent of PNNs, but the specific roles of Sema3A in modulating PV-INs during stress remain unknown.
View Article and Find Full Text PDFMol Psychiatry
September 2025
Department of Pharmacological and Biomolecular Sciences "Rodolfo Paoletti", Università degli Studi di Milano, Milan, Italy.
Early-life experiences shape neural networks, with heightened plasticity during the so-called "sensitive periods" (SP). SP are regulated by the maturation of GABAergic parvalbumin-positive (PV+) interneurons, which become enwrapped by perineuronal nets (PNNs) over time, modulating SP closure. Additionally, the opening and closing of SP are orchestrated by two distinct gene clusters known as "trigger" and "brake".
View Article and Find Full Text PDFNeuropsychopharmacology
September 2025
Neuroscience Center, HiLIFE, University of Helsinki, Helsinki, Finland.
Chronic treatment with fluoxetine, a widely prescribed selective serotonin reuptake inhibitor (SSRI), is known to promote neural plasticity. The role of fluoxetine in plasticity has been particularly tied to parvalbumin-positive interneurons, a key population of GABAergic neurons that regulate inhibitory tone and network stability. While our previous studies have highlighted fluoxetine-induced plasticity in the visual cortex and hippocampus, its cell-type-specific effects in the prefrontal cortex (PFC) remain unclear.
View Article and Find Full Text PDFMol Psychiatry
September 2025
Department of Neurology, Zhongshan Hospital of Xiamen University, and Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, School of Medicine, Xiamen University, Xiamen, Fujian, 361102, China.
Atrophy of the subiculum is the earliest hippocampal anatomical marker of Alzheimer's disease (AD) and is closely associated with early cognitive decline. However, the underlying mechanisms driving this vulnerability remain unclear. In this study, using the 5×FAD mouse model, we identified significant amyloid-beta (Aβ) accumulation in the subiculum during the early stages of AD.
View Article and Find Full Text PDFbioRxiv
August 2025
Department of Neuroscience and Physiology.
Cannabidiol (CBD) decreases seizures in patients with severe pediatric-onset epilepsies including Dravet, Lennox-Gastaut, and Tuberous Sclerosis syndromes. However, the effects of CBD on neuronal activity and circuits remain obscure. In the mouse hippocampus, we found that CBD causes a GPR55-independent decrease in CA1 pyramidal neuron firing frequency and a GPR55-dependent reduction in CA3 to CA1 hippocampal activity propagation.
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