scholarly journals High-Dose Dexmedetomidine Promotes Apoptosis in Fetal Rat Hippocampal Neurons

2021 ◽  
Vol Volume 15 ◽  
pp. 2433-2444
Author(s):  
Qiufeng Wei ◽  
Jing Chen ◽  
Fei Xiao ◽  
Youbing Tu ◽  
Yu Zhong ◽  
...  
Keyword(s):  
Hippocampal Neurons ◽  
High Dose ◽  
Fetal Rat

scholarly journals The Dose-dependent Dual Effects of Corticosterone on Spatial Memory Ability After Traumatic Brain Injury Are Mediated by Two Corticosteroid Receptor Systems

2021 ◽  
Author(s):  
Bin Zhang ◽  
Mengshi Yang ◽  
Qiongyu Yan ◽  
Xiaojian Xu ◽  
Fei Niu ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Spatial Memory ◽  
Signaling Pathways ◽  
Hippocampal Neurons ◽  
High Dose ◽  
Short Term ◽  
Memory Ability ◽  
Neurotoxic Effects ◽  
Dose Dependent

Abstract Background: Our recent studies reported the opposite effects of mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) on neuron survival after traumatic brain injury (TBI). However, as a mixed agonist for MR and GR, whether short term use of high-dose endogenous glucocorticoids exerts neurotoxic effects by excessive activation of GR, what is the set-point, and the possible signaling pathways remain unclear. This study examined the dose-dependent dual effects of corticosterone (CORT) on the spatial memory, the survival of hippocampal neurons and the possible receptor-mediated downstream signaling pathways after TBI.Methods: Based on controlled cortical impact (CCI) and CORT treatments, Sprague-Dawley rats (n=168) were randomly divided into the sham, CCI, CCI + CORT1 (0.3 mg/kg), CCI + CORT2 (3 mg/kg), CCI + CORT3 (30 mg/kg), CCI + CORT1 + spirolactone (spirolactone: 50 mg/kg/d), and CCI + CORT3 + RU486 (RU486: 50 mg/kg/d) groups. Brain tissues were collected on postinjury day 3 and processed for histology and western blot analysis.Results: On postinjury day 3, we tested the learning and memory ability, neuronal apoptosis in the hippocampus, activation levels of MR and GR, Bcl-2 family proteins, and apoptosis-related intracellular signaling pathways. We found that different doses of CORT exhibited dual effects on the survival of hippocampal neurons and the spatial memory. Lower doses of CORT (0.3, 3 mg/kg) significantly increased the activation of MR, upregulated the phosphorylation of Akt/CREB/Bad and the Bcl-2 expression, reduced the number of apoptotic neurons, and subsequently improved the spatial memory. In contrast, higher dose of CORT (30 mg/kg) exerted opposite effect by over activating GR, upregulating the expressions of P53/Bax, and inhibiting the Erk/CREB activities. Conclusion: The results suggest that there is a threshold between the neuroprotective and neurotoxic effects of endogenous GC, higher dose of which, even for short-term use, should also be avoided after TBI.

Cl−/HCO3− exchange function differs in adult and fetal rat hippocampal neurons

1993 ◽  
Vol 614 (1-2) ◽  
pp. 308-314 ◽  
Author(s):  
Kathleen M. Raley-Susman ◽  
Robert M. Sapolsky ◽  
Ron R. Kopito
Keyword(s):  
Hippocampal Neurons ◽  
Fetal Rat ◽  
Exchange Function

scholarly journals 11beta-hydroxylase and aldosterone synthase expression in fetal rat hippocampal neurons

2002 ◽  
Vol 29 (3) ◽  
pp. 319-325 ◽  
Author(s):  
SM MacKenzie ◽  
M Lai ◽  
CJ Clark ◽  
R Fraser ◽  
CE Gomez-Sanchez ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Hippocampal Neurons ◽  
Primary Cultures ◽  
Local System ◽  
Model System ◽  
Biochemical Reactions ◽  
Aldosterone Synthase ◽  
Fetal Rat ◽  
The Central Nervous System

The central nervous system produces many of the enzymes responsible for corticosteroid synthesis. A model system to study the regulation of this local system would be valuable. Previously, we have shown that primary cultures of hippocampal neurons isolated from the fetal rat can perform the biochemical reactions associated with the enzymes 11beta-hydroxylase and aldosterone synthase. Here, we demonstrate directly that these enzymes are present within primary cultures of fetal rat hippocampal neurons.

scholarly journals Dose and Temporal Pattern of Estrogen Exposure Determines Neuroprotective Outcome in Hippocampal Neurons: Therapeutic Implications

Endocrinology ◽  
2006 ◽  
Vol 147 (11) ◽  
pp. 5303-5313 ◽  
Author(s):  
Shuhua Chen ◽  
Jon Nilsen ◽  
Roberta Diaz Brinton
Keyword(s):  
Intracellular Calcium ◽  
Temporal Pattern ◽  
Hippocampal Neurons ◽  
Estrogen Therapy ◽  
Therapeutic Benefit ◽  
High Dose ◽  
Therapeutic Implications ◽  
Estrogen Exposure ◽  
The Impact

To address controversies of estrogen therapy, in vitro models of perimenopause and prevention vs. treatment modes of 17β-estradiol (E2) exposure were developed and used to assess the neuroprotective efficacy of E2 against β-amyloid-1–42 (Aβ1–42)-induced neurodegeneration in rat primary hippocampal neurons. Low E2 (10 ng/ml) exposure exerted neuroprotection in each of the perimenopausal temporal patterns, acute, continuous, and intermittent. In contrast, high E2 (200 ng/ml) was ineffective at inducing neuroprotection regardless of temporal pattern of exposure. Although high E2 alone was not toxic, neurons treated with high-dose E2 resulted in greater Aβ1–42-induced neurodegeneration. In prevention vs. treatment simulations, E2 was most effective when present before and during Aβ1–42 insult. In contrast, E2 treatment after Aβ1–42 exposure was ineffective in reversing Aβ-induced degeneration, and exacerbated Aβ1–42-induced cell death when administered after Aβ1–42 insult. We sought to determine the mechanism by which high E2 exacerbated Aβ1–42-induced neurodegeneration by investigating the impact of low vs. high E2 on Aβ1–42-induced dysregulation of calcium homeostasis. Results of these analyses indicated that low E2 significantly prevented Aβ1–42-induced rise in intracellular calcium, whereas high E2 significantly increased intracellular calcium and did not prevent Aβ1–42-induced calcium dysregulation. Therapeutic benefit resulted only from low-dose E2 exposure before, but not after, Aβ1–42-induced neurodegeneration. These data are relevant to impact of perimenopausal E2 exposure on protection against neurodegenerative insults and the use of estrogen therapy to prevent vs. treat Alzheimer’s disease. Furthermore, these data are consistent with a healthy cell bias of estrogen benefit.

Corticosteroid Production by Fetal Rat Hippocampal Neurons

2000 ◽  
Vol 26 (4) ◽  
pp. 531-535 ◽  
Author(s):  
S. M. Mackenzie ◽  
C. J. Clark ◽  
M. C. Ingram ◽  
M. Lai ◽  
J. Seckl ◽  
...  
Keyword(s):  
Hippocampal Neurons ◽  
Fetal Rat

scholarly journals Xiao-Yao-San Formula Improves Cognitive Ability by Protecting the Hippocampal Neurons in Ovariectomized Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Lina Liu ◽  
Fei Ge ◽  
Haoran Yang ◽  
Huilian Shi ◽  
Weiting Lu ◽  
...  
Keyword(s):  
Western Blot ◽  
Learning And Memory ◽  
Cognitive Abilities ◽  
Hippocampal Neurons ◽  
Ovariectomized Rats ◽  
Tunel Staining ◽  
High Dose ◽  
Pi3k Signaling ◽  
Hippocampal Ca1 ◽  
Golgi Staining

Xiao-Yao-San (XYS) decoction is a traditional Chinese medicine formula. This study aimed to investigate the effect of XYS on cognitive abilities and its underlying mechanism in ovariectomized rats. Female Sprague-Dawley rats were ovariectomized and treated with XYS (3 g/kg or 9 g/kg) by gavage, with subcutaneous injection of 17-β estradiol (E2, 2 μg/kg) as a positive drug control and gavage of 1 ml saline (0.9%) as a placebo control. After 6 weeks of treatment, rats were examined using the Morris water maze test. The estradiol level in the serum and hippocampus was measured by ELISA. Golgi staining was performed to observe neuronal morphology in the hippocampus. Apoptosis of hippocampal cells was observed by TUNEL staining. The protein content of N-methyl-D-aspartate receptor (NMDAR) 2A and 2B in the hippocampal CA1 region was determined by Western blot and immunohistochemistry. Expression of estrogen receptor (ER) and PI3K signaling was detected by Western blot. Compared with the sham group, both learning and memory were impaired in ovariectomized rats. Rats treated with E2 or high-dose XYS showed better learning and memory compared with the saline-treated rats. High-dose XYS significantly reduced escape latency in the spatial acquisition trial; meanwhile, the cross times and duration in the probe quadrant were increased in the spatial probe trial. High-dose XYS promoted the de novo synthesis of E2 content in the hippocampus but had no significant effect on the serum E2 level. Golgi staining indicated that high-dose XYS could increase the branch number and density of dendritic spines in the hippocampal CA1 area. TUNEL staining showed that high-dose XYS alleviated ovariectomy-induced neuronal apoptosis. The expression level of NMDAR2A and NMDAR2B in hippocampal CA1 was upregulated by XYS treatment. The beneficial effect of XYS was through activating ERα-PI3K signaling. In conclusion, high-dose XYS treatment can improve the cognitive abilities of ovariectomized rats by protecting the hippocampal neurons and restoring the hippocampal E2 level.

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