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Objective: To observe the effect of moxibustion at Governor Vessel acupoints on inositol requiring enzyme 1 (IRE1) / X-box binding protein 1 (XBP1) pathway in hippocampal CA1 region of rats with vascular dementia (VD), so as to explore its mechanisms in the treatment of VD.
Methods: Male SD rats were randomly divided into normal, sham operation, model, moxibustion (Moxi) and medication groups (n=12). The VD model was established by permanent ligation of bilateral common carotid arteries. For rats of the Moxi group, mild moxibustion was given to "Baihui" (GV20), "Dazhui" (GV14) and "Fengfu" (GV16) for 20 min each point, once a day for consecutive 6 days per week, for a total of 4 weeks. For rats of the medication group, intragastric perfusion of nimodipine was given 3 times each day with total dose of 2 mg•kg•d for 4 weeks. Morris water maze test was used to detect the learning and memory ability of rats before and after modeling as well as after intervention. The apoptosis rate of nerve cells in hippocampal CA1 region was detected by TUNEL staining. The proteins and mRNA expression levels of IRE1, XBP1, B-cell lymphoma/leukemia-2 (Bcl-2), Bcl-2 associated X protein (Bax) in hippocampal CA1 region were detected by Western blot and real-time quantitative PCR, respectively.
Results: Compared with the sham operation group, the average escape latency was significantly prolonged (<0.01), the number of times crossing the original platform was significantly reduced (<0.01), the apoptosis rate of nerve cells in hippocampal CA1 region was significantly increased (<0.01), the proteins and mRNA expression levels of IRE1, XBP1 and Bax were significantly increased (<0.01), and the expression levels of Bcl-2 protein and mRNA were significantly decreased (<0.01) in rats of the model group. After treatment, compared with the model group, the average escape latency was significantly shortened (<0.01), the number of times crossing the original platform was increased (<0.05), the apoptosis rate of nerve cells in hippocampal CA1 region was significantly decreased (<0.01), the protein and mRNA expression levels of IRE1, XBP1 and Bax were decreased (<0.05, <0.01), and the expression levels of Bcl-2 protein and mRNA were increased (<0.05, <0.01) in rats of the Moxi group and medication group. There was no significant difference in the above indexes between the Moxi group and the medication group.
Conclusion: Moxibustion at the acupoints of Governor Vessel can improve the cognitive function of VD rats, and its mechanism may be related to regulating IRE1/XBP1 pathway, inhibiting the release of pro-apoptotic protein Bax, increasing the expression of anti-apoptotic protein Bcl-2, and thus inhibiting the apoptosis of hippocampal nerve cells.
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http://dx.doi.org/10.13702/j.1000-0607.20221167 | DOI Listing |
EMBO J
September 2025
Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan.
During a critical period of postnatal brain development, neural circuits undergo significant refinement coincident with widespread alternative splicing of hundreds of genes, which undergo altered splice site selection for the generation of isoforms essential for synaptic plasticity. Here, we reveal that neuronal activity-dependent phosphorylation of paxillin at its serine 119 (p-paxillin) acts as a molecular switch in the nucleus for the control of alternative splicing during this period. We show that following NMDA receptor activation, nuclear p-paxillin is recruited to nuclear speckles, where it interacts with splicing factors, such as U2AFs.
View Article and Find Full Text PDFPharmacol Biochem Behav
September 2025
Departamento de Psicobiología y Metodología de las Ciencias del Comportamiento, Universidad de Málaga (UMA), Málaga, 29010, Spain; Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina (IBIMA Plataforma BIONAND), Málaga, Spain. Electronic address:
Adolescence is a period of heightened neuroplasticity and vulnerability to environmental insults, including drug exposure. In this study, we investigated the short- and long-term behavioral effects, as well as the long-term hippocampal effects, of chronic cocaine administration during adolescence, along with the potential neuroprotective role of insulin-like growth factor 2 (IGF2) in male C57BL/6J mice. Over 21 days, mice received daily intraperitoneal injections of saline, cocaine, IGF2, or a combination of cocaine and IGF2.
View Article and Find Full Text PDFAsian J Psychiatr
September 2025
National-Local Joint Engineering Research Center of Rehabilitation Medicine Technology, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China; Rehabilitation Industry Institute, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China; Traditional Chinese Medicine Re
Background: Amnestic mild cognitive impairment (aMCI) is characterized by marked episodic memory decline. The hippocampus is essential for episodic memory, and integration of information within its subregions is central to this process. This study examined how alterations in hippocampal subregional network relate to episodic memory impairment in aMCI.
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.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
September 2025
Institut de Biologie de l'Ecole Normale Supérieure, Ecole Normale Supérieure, Université Paris Sciences et Lettres, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Paris 75005, France.
Excitatory glycine receptors (eGlyRs), composed of the glycine-binding NMDA receptor subunits GluN1 and GluN3A, have recently emerged as a novel neuronal signaling modality that challenges the traditional view of glycine as an inhibitory neurotransmitter. Unlike conventional GluN1/GluN2 NMDARs, the distribution and role of eGlyRs remain poorly understood. Here, we show that eGlyRs are highly enriched in the ventral hippocampus (VH) and confer distinct properties on this brain region.
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