scholarly journals Bacopa monnieri extract improves novel object recognition, cell proliferation, neuroblast differentiation, brain-derived neurotrophic factor, and phosphorylation of cAMP response element-binding protein in the dentate gyrus

2018 ◽  
Vol 34 (4) ◽  
pp. 239 ◽  
Author(s):  
Hyun Jung Kwon ◽  
Hyo Young Jung ◽  
Kyu Ri Hahn ◽  
Woosuk Kim ◽  
Jong Whi Kim ◽  
...  
2019 ◽  
Vol 35 (1) ◽  
Author(s):  
Hyun Jung Kwon ◽  
Woosuk Kim ◽  
Hyo Young Jung ◽  
Min Soo Kang ◽  
Jong Whi Kim ◽  
...  

Abstract In the present study, we investigated the effects of heat shock protein 70 (HSP70) on novel object recognition, cell proliferation, and neuroblast differentiation in the hippocampus. To facilitate penetration into the blood–brain barrier and neuronal plasma membrane, we created a Tat-HSP70 fusion protein. Eight-week-old mice received intraperitoneal injections of vehicle (10% glycerol), control-HSP70, or Tat-HSP70 protein once a day for 21 days. To elucidate the delivery efficiency of HSP70 into the hippocampus, western blot analysis for polyhistidine was conducted. Polyhistidine protein levels were significantly increased in control-HSP70- and Tat-HSP70-treated groups compared to the control or vehicle-treated group. However, polyhistidine protein levels were significantly higher in the Tat-HSP70-treated group compared to that in the control-HSP70-treated group. In addition, immunohistochemical study for HSP70 showed direct evidences for induction of HSP70 immunoreactivity in the control-HSP70- and Tat-HSP70-treated groups. Administration of Tat-HSP70 increased the novel object recognition memory compared to untreated mice or mice treated with the vehicle. In addition, the administration of Tat-HSP70 significantly increased the populations of proliferating cells and differentiated neuroblasts in the dentate gyrus compared to those in the control or vehicle-treated group based on the Ki67 and doublecortin (DCX) immunostaining. Furthermore, the phosphorylation of cAMP response element-binding protein (pCREB) was significantly enhanced in the dentate gyrus of the Tat-HSP70-treated group compared to that in the control or vehicle-treated group. Western blot study also demonstrated the increases of DCX and pCREB protein levels in the Tat-HSP70-treated group compared to that in the control or vehicle-treated group. In contrast, administration of control-HSP70 moderately increased the novel object recognition memory, cell proliferation, and neuroblast differentiation in the dentate gyrus compared to that in the control or vehicle-treated group. These results suggest that Tat-HSP70 promoted hippocampal functions by increasing the pCREB in the hippocampus.


2019 ◽  
Vol 20 (1) ◽  
pp. 188 ◽  
Author(s):  
Alexis Howe ◽  
Frederico Kiffer ◽  
Tyler C. Alexander ◽  
Vijayalakshmi Sridharan ◽  
Jing Wang ◽  
...  

Astronauts traveling to Mars will be exposed to high levels of ionizing radiation upon leaving low-Earth orbit. During prolonged space travel, astronauts are exposed to galactic cosmic rays (GCRs) composed of protons; oxygen molecules; and high energy, high mass charged particles. Notably, oxygen molecules can travel through the shielding of spacecraft, potentially impacting 25% of the hippocampus. The aim of the current study was to assess whether 16O-particle radiation induced a behavioral deficit and histological changes in mice. Mice were sent to the National Aeronautics and Space Administration (NASA) Space Radiation Laboratory at Brookhaven National Laboratory and exposed to particulate 16O radiation at doses of 0 and 0.05 Gy. Nine months after irradiation, the mice were tested for novel object recognition and in the Y-maze, after which the animals were sacrificed. The brains were then dissected along the midsagittal plane for Golgi staining. Exposure to 0.05 Gy significantly impaired novel object recognition. However, short term memory and exploratory activity in the Y-maze were not affected. Micromorphometric analysis revealed significant decreases in mushroom spine density in the dentate gyrus and cornu Ammonis-1 and -3 of the hippocampus. Sholl analysis revealed a significant decrease in dendritic complexity in the dentate gyrus. The present data provide evidence that space radiation has deleterious effects on mature neurons associated with hippocampal learning and memory.


2018 ◽  
Vol 30 (8) ◽  
pp. 1145 ◽  
Author(s):  
A. V. Sirotkin ◽  
A. Benčo ◽  
A. Tandlmajerová ◽  
M. Lauková ◽  
D. Vašíček ◽  
...  

The aim of the present study was to examine the role of cAMP response element-binding protein (CREB) and its phosphorylation in the regulation of ovarian cell proliferation and apoptosis, and of the response of proliferation and apoptosis to the upstream hormonal stimulators FSH and insulin-like growth factor (IGF) 1. In the first series of experiments, porcine ovarian granulosa cells, transfected or not with a gene construct encoding wild-type CREB1 (CREB1WT), were cultured with and without FSH (0, 1, 10 or 100 ng mL−1). In the second series of experiments, these cells were transfected or not with CREB1WT or non-phosphorylatable mutant CREB1 (CREB1M1) and cultured with and without FSH (0, 1, 10 or 100 ng mL−1) or IGF1 (0, 1, 10 and 100 ng mL−1). Levels of total and phosphorylated (p-) CREB1, proliferating cell nuclear antigen (PCNA), a marker of proliferation, and BAX, a marker of apoptosis, were evaluated by western immunoblotting and immunocytochemical analysis. Transfection of cells with CREB1WT promoted accumulation of total CREB1 within cells, but p-CREB1 was not detected in any cell group. Both CREB1WT and CREB1M1 reduced cell proliferation and apoptosis. Addition of 10 and 100 ng mL−1 FSH to non-transfected cells promoted CREB1 accumulation and apoptosis, whereas cell proliferation was promoted by all concentrations of FSH tested. FSH activity was not modified in cells transfected with either CREB1WT or CREB1M1. IGF1 at 100 ng mL−1 promoted cell proliferation, whereas all concentrations of IGF1 tested reduced apoptosis. Transfection with either CREB1WT or CREB1M1 did not modify the effects of either FSH or IGF1, although CREB1M1 reversed the effect of IGF1 on apoptosis from inhibitory to stimulatory. These observations suggest that CREB1 is involved in the downregulation of porcine ovarian cell proliferation and apoptosis. The absence of visible CREB1 phosphorylation and the similarity between the effects of CREB1WT and CREB1M1 transfection indicate that phosphorylation is not necessary for CREB1 action on these processes. Furthermore, the observations suggest that FSH promotes both ovarian cell proliferation and apoptosis, whereas IGF1 has proliferation-promoting and antiapoptotic properties. The effect of FSH on CREB1 accumulation and the ability of CREB1M1 to reverse the effects of IGF1 on apoptosis indicate that CREB1 is a mediator of hormonal activity, but the inability of either CREB1WT or CREBM1transfection to modify the primary effects of FSH and IGF1 suggest that CREB1 and its phosphorylation do not mediate the action of these hormones on ovarian cell proliferation and apoptosis.


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