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The brain of Down syndrome (DS) patients exhibits fewer interneurons in the cerebral cortex, but its underlying mechanism remains unknown. By morphometric analysis of cortical interneurons generated from DS and euploid induced pluripotent stem cells (iPSCs), we found that DS GABA neurons are smaller and with fewer neuronal processes. The proportion of calretinin over calbindin GABA neurons is reduced, and the neuronal migration capacity is decreased. Such phenotypes were replicated following transplantation of the DS GABAergic progenitors into the mouse medial septum. Gene expression profiling revealed altered cell migratory pathways, and correction of the PAK1 pathway mitigated the cell migration deficit in vitro. These results suggest that impaired migration of DS GABAergic neurons may contribute to the reduced number of interneurons in the cerebral cortex and hippocampus in DS patients.
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http://dx.doi.org/10.1016/j.stemcr.2018.02.001 | DOI Listing |
Alcohol Clin Exp Res (Hoboken)
September 2025
Department of Neuroscience and Experimental Therapeutics, Penn State College of Medicine, Hershey, Pennsylvania, USA.
Background: Prenatal alcohol exposure (PAE) causes fetal alcohol spectrum disorder (FASD) and is associated with various cognitive and sensory impairments, including olfactory dysfunction. While both genetic and environmental factors contribute to olfactory dysfunction, PAE is considered a significant factor affecting brain development, including the olfactory system. In this study, we investigated the impact of PAE on the developing olfactory bulb (OB), specifically focusing on OB RGCs-radial glial cells that give rise to OB projection neurons.
View Article and Find Full Text PDFStem Cell Reports
September 2025
Regenerative Neurophysiology, Lund Stem Cell Centre, MultiPark Strategic Area in Neuroscience, Department of Experimental Medical Science, Faculty of Medicine, Lund University, 221 84 Lund, Sweden. Electronic address:
Cortical interneuron deficiencies, particularly involving the somatostatin (SST) subtypes, contribute to neurological and neuropsychiatric disorders. These interneurons are difficult to derive in vitro from human embryonic stem cells (hESCs) due to their late embryonic development and dependence on glial interaction. To this end, we developed a three-dimensional co-culture model of hESC-derived neurons, enabling long-term development, functional maturity, and neuron-glial interaction.
View Article and Find Full Text PDFZhejiang Da Xue Xue Bao Yi Xue Ban
September 2025
Institute of Brain Science and Disease Research Institute, Qingdao University, Qingdao 266075, Shandong Province, China.
Objectives: To investigate the role of a neural pathway from oxytocin (OXT) neurons in the hypothalamic paraventricular nucleus (PVN) to γ-aminobutyric acid (GABA) neurons in the trigeminal nucleus caudalis (TNC) in regulating pain sensitization in a mouse model of chronic migraine and to explore the underlying mechanisms.
Methods: A chronic migraine model was established by intraperitoneal injection of nitroglycerin (NTG, 10 mg/kg) on days 1, 3, 5, 7, and 9. The study consisted of four parts: PartⅠ: Wild-type C57BL/6J mice were divided into 4 groups (=6 in each), receiving single or repeated injection of NTG or saline, respectively.
J Neurosci
September 2025
Lendület Laboratory of Thalamus Research, HUN-REN Institute of Experimental Medicine; Budapest, Hungary
The paraventricular thalamic nucleus (PVT) integrates subcortical signals related to arousal, stress, addiction, and anxiety with top-down cortical influences. Increases or decreases in PVT activity exert profound, long-lasting effects on behavior related to motivation, addiction and homeostasis. Yet the sources of its subcortical excitatory and inhibitory afferents, their distribution within the PVT, and their integration with layer-specific cortical inputs remain unclear.
View Article and Find Full Text PDFJ Neurophysiol
September 2025
Department of Neurosurgery, University of Utah School of Medicine, Salt Lake City, UT, USA.
Although glutamatergic and GABAergic synapses are important in seizure generation, the contribution of non-synaptic ionic and electrical mechanisms to synchronization of seizure-prone hippocampal neurons remains unclear. Here, we developed a physiologically relevant model to study these mechanisms by inducing prolonged seizure-like discharges (SLDs) in hippocampal slices from male rats through modest, sustained ionic manipulations. Specifically, we reduced extracellular calcium to 0.
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