Cranial radiation impairs neuroplasticity along the hippocampal-PFC pathway; however, its effects vary by age. Pretreatment with memantine offered protection to both juvenile and adult animals. Deficits in cortical plasticity may contribute to radiation-induced cognitive dysfunction, including deficits in attention and age-dependent sensitivity of such pathways, which may underlie differences in clinical outcomes between juveniles and adults after cranial irradiation.
Background Radiation therapy for brain tumors commonly induces cognitive dysfunction. The prefrontal cortex (PFC) is crucial for a diverse array of cognitive processes, however, its role in radiation-induced cognitive dysfunction is unknown. We previously found that cranial irradiation impairs neuroplasticity along the hippocampal–PFC pathway. Herein, we hypothesized that brain irradiation directly affects the firing properties of PFC neurons, contributing to deficits in neuronal functions. Methods In vivo recordings were used to monitor the firing activities of PFC neurons and local field potentials in both PFC and hippocampal CA1/subicular regions after cranial irradiation of Sprague Dawley rats. We further assessed the impacts of irradiation on axon initial segments (AISs) with immunofluorescence assays of PFC slices. Results We found that PFC neurons exhibited increased excitation 3 days after radiation and the timing of increased excitation coincided with elongation of the AIS. At 2 weeks, excitation levels returned to nearly normal levels however the population of spontaneously firing neurons decreased. While the number of NeuN-positive neurons in the PFC was not different, persistent neuronal injury, manifested as ATF-3 staining, was present at 2 weeks. Radiation also disrupted communication along the hippocampal–PFC pathway, with elongation of the phase lag between regions. Analysis of paired-pulse ratios suggested that this was secondary to presynaptic dysfunction. Conclusions Cranial irradiation excited and injured surviving PFC neurons and was associated with a partial block of PFC’s functional coupling to the hippocampus. These deficits in the PFC may contribute to radiation-induced cognitive dysfunction.
Introduction: Panax vietnamensis Ha et Grushv. (Ngoc Linh ginseng)-a new species recently discovered in Vietnam-has received much interest due to its rich content of saponins, including those unknown. This study assessed the effects of the Ngoc Linh ginseng extract fractions on proliferation and differentiation of cultured mouse neural stem cells. Methods: Whole brains were harvested from E13.5-14 Swiss mouse fetuses. Isolated cells were floating seeded to form spheroid bodies. Neurospheres were treated with one in fractions of ethanol 200-500 µg/mL, or n-butanol 200 µg/mL, or aqueous 200-500 µg/mL for 5 days. Neural stem cells could persistently generate secondary spheres. Neurospheres strongly expressed nestin, CD24 and deriving cells could differentiate into the GFAP-positive astrocyte-like cells. Results: Ginseng fractions significantly promoted neurosphere growth rate. Particularly, 200 µg/mL ginseng ethanol fraction significantly increased the neurosphere size (28.00±3.00%, p<0.0001) not showing degeneration to the 5 th day. However, n-butanol and aqueous fraction could not sustain the sphere structure. Ginseng ethanol fraction also elevated in the G2/M proportion (28.73±0.45%, p<0.0001), up-regulated proliferation mRNA ki67 (4.605±6.48 fold-change, p<0.05), cycA1 (12.61±4.65 fold-change, p<0.0001), cycD1 (22.47±8.18 fold-change, p<0.0001), cycC (9.53±2.63 fold-change, p<0.0001) compared with those of the n-butanol or aqueous fraction-treated neurospheres. Shorten G0/G1 phase (47.08± 0.16, p<0.0001), up-regulation of sox2 (71.25±27.24 fold-change, p<0.0001) mRNA levels indicated selfrenewal effect of the ginseng ethanol fraction; however, those of n-butanol and aqueous fractiontreated neurospheres suggested an inhibiting effect on the cell proliferation. Conclusion: Panax vietnamensis extract fractions had a positive effect on the proliferation of cultured neural stem cells. The ethanol fraction at 200 µg/mL could significantly promote the growth rate while still sustained the integrity of treated spheres.
Background:Ginseng has been known since ancient time for its unique pharmaceutical effects on human health. Modern studies indicated that extracts of ginseng could improve a broad range of pathological conditions including neurodegenerative diseases such as Alzheimer's or Parkinson's disease. Panax vietnamensis, a new ginseng species recently discovered in Vietnam, has received much interest due to its high composition of both known and new saponins whose therapeutic effects have not yet fully evaluated. In this study, the proliferative and differentiative effects of different fractions of the extract of Panax vietnamensis on cultured neural stem cells would be assessed.
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