Protective Effect of Butylphthalide on Neuronal Apoptosis in Parkinson Rats and Its Effect on miR-146a-5p Expression and Phosphatidylinositide 3-Kinases/Protein Kinase B Pathway

2021 ◽  
Vol 11 (10) ◽  
pp. 1908-1917
Author(s):  
Rongkang Mai ◽  
Yiyao Cao ◽  
Huitian Yu ◽  
Yong Zheng ◽  
Juke Huang

80 male Wistar rats were stochastically assigned to Sham + Vehicle group, Sham + BUT group, PD + Vehicle group and PD + BUT group. Rotenone PD model rats were prepared by subcutaneous injection of rotenone sunflower oil emulsion 2 mg/(kg · d) for 5 consecutive weeks. Butylphthalide 80 mg/(kg · d) were given to the rats in Sham + BUT group and PD + BUT group by gavage from the first day of rotenone injection for 5 weeks. Subsequently, the motor retardation ability and the morphological changes of the substantia nigra (SN) of each group were evaluated. Meanwhile, the levels of neuronal injury, apoptosis, inflammation and oxidative stress in each group of rats were assayed. The impact of BUT treatment on miR-146a-5p expression and PI3K/AKT signal pathway in rat brain tissue was assayed. Finally, by constructing a PD cell model of the neurotoxin 6-hydroxydopamine (6-OHDA)-treated human neuroblastoma cell line SH-SY5Y, the in vitro anti-PD pharmacological effect of BUT was further verified.

2019 ◽  
Vol 45 (6) ◽  
pp. 1399-1409
Author(s):  
Nafisa Ferdous ◽  
Sirisha Kudumala ◽  
Serena Sossi ◽  
Lucia Carvelli

AbstractAmphetamine (AMPH) is a systemic stimulant used to treat a variety of diseases including Attention Deficit Hyperactive Disorder, narcolepsy and obesity. Previous data showed that by binding to catecholamine transporters, AMPH prevents the reuptake of the neurotransmitters dopamine (DA) and norepinephrine (NE). Because AMPH, either used therapeutically at final concentrations of 1–10 µM or abused as recreational drug (50–200 µM), is taken over long periods of time, we investigated the prolonged effects of this drug on the uptake of DA. We found that, in LLC-PK1 cells stably expressing the human DA transporter (hDAT), pretreatments with 1 or 50 µM AMPH caused significant reduction in DA uptake right after the 15-h pretreatment. Remarkably, after 50 but not 1 µM AMPH pretreatment, we observed a significant reduction in DA uptake also after one, two or three cell divisions. To test whether these long-term effects induced by AMPH where conserved in a model comparable to primordial neuronal cells and native neurons, we used the human neuroblastoma cell line SH-SY5Y cells, which were reported to endogenously express both hDAT and the NE transporter. Pretreatments with 50 µM AMPH caused a significant reduction of DA uptake both right after 15 h and 3 cell divisions followed by neuro-differentiation with retinoic acid (RA) for 5 days. Under these same conditions, AMPH did not change the intracellular concentrations of ATP, ROS and cell viability suggesting, therefore, that the reduction in DA uptake was not cause by AMPH-induced toxicity. Interestingly, while 1 µM AMPH did not cause long-term effects in the LLC-PK1 cells, in the SH-SY5Y cells, it decreased the DA uptake after one, two, but not three, cell divisions and 5-day RA differentiation. These data show that besides the well-known acute effects, AMPH can also produce long-term effects in vitro that are maintained during cell division and transmitted to the daughter cells.


1996 ◽  
Vol 76 (6) ◽  
pp. 3920-3927 ◽  
Author(s):  
M. Toselli ◽  
P. Tosetti ◽  
V. Taglietti

1. The electrophysiological properties of voltage-dependent sodium currents were studied in the human neuroblastoma cell line SH-SY5Y before and after in vitro differentiation with retinoic acid, with the use of the whole cell variant of the patch-clamp technique. 2. Voltage steps from a holding level of -90 mV to depolarizing potentials elicited, in both undifferentiated and differentiated cells, fast inward sodium currents that were full inactivating and tetrodotoxin sensitive. 3. In undifferentiated cells the current peaked at -10 mV, the half-activation potential was -35 mV, and the half-inactivation potential was -81 mV. In differentiated cells the current peaked at + 10 mV, the half-activation potential was -28 mV, and the half-inactivation potential was -56 mV. Moreover, the peak current amplitude was about a factor of 2 larger and inactivation kinetics was about a factor of 2 slower than in undifferentiated cells. 4. This diversity in sodium channel properties was related to differences in cell excitability. Under current-clamp conditions, intracellular injection of rectangular depolarizing current stimuli from a hyperpolarized membrane potential of about -100 mV elicited graded and weak regenerative responses in undifferentiated cells, whereas overshooting action potentials with faster rising phases could be elicited in differentiated cells.


2008 ◽  
Vol 8 (12) ◽  
pp. 6223-6231 ◽  
Author(s):  
Gianni Ciofani ◽  
Vittoria Raffa ◽  
Arianna Menciassi ◽  
Paolo Dario

While in the last years applications of carbon nanotubes in the field of biotechnology have been largely proposed, biomedical applications of boron nitride nanotubes (BNNTs) are yet totally unexplored. BNNTs have very interesting physical properties that should be exploited in the biomedical field. At this date, studies on their biocompatibility are completely missing and the first issue behind this investigation is the dispersion of BNNTs in aqueous solutions. In this paper the authors propose, for the first time, a technique for obtaining BNNT stable dispersions suitable for biological applications, based on polyethyleneimine (PEI) water solutions. Based on authors' knowledge, in vitro testing performed on human neuroblastoma cell line (SH-SY5Y) is the first study of interaction between BNNTs and living material. Experimental results showed a satisfactory cell viability up to a concentration of 5.0 μg/ml PEI-BNNTs in the cell culture medium.


2016 ◽  
Vol 2016 ◽  
pp. 1-9
Author(s):  
Noor Azuin Suliman ◽  
Mohamad Aris Mohd Moklas ◽  
Che Norma Mat Taib ◽  
Mohd Ilham Adenan ◽  
Mohamad Taufik Hidayat Baharuldin ◽  
...  

Opiate abuse has been studied to cause adaptive changes observed in the presynaptic release and the mediated-synaptic plasticity proteins. The involvement of neuronal SNARE proteins reveals the role of the neurotransmitter release in expressing the opioid actions. The present study was designed to determine the effect of the alkaloid extract ofErythroxylum cuneatum(E. cuneatum) against chronic morphine and the influences ofE. cuneatumon neurotransmission processes observedin vitro. The human neuroblastoma cell line, SK-N-SH, was treated with the morphine, methadone, orE. cuneatum. The cell lysates were collected and tested forα-synuclein, calmodulin, vesicle-associated membrane protein 2 (VAMP 2), and synaptotagmin 1. The extract ofE. cuneatumwas observed to upregulate the decreased expression of dependence proteins, namely,α-synuclein and calmodulin. The effects were comparable to methadone and control. The expressions of VAMP 2 and synaptotagmin 1 were normalised by the plant and methadone. The extract ofE. cuneatumwas postulated to treat dependence symptoms after chronic morphine and improve the soluble N-ethylmaleimide-sensitive factor activating protein receptor (SNARE) protein involved in synaptic vesicle after.


2013 ◽  
Vol 29 (5) ◽  
pp. 1714-1720 ◽  
Author(s):  
M. WAHEED ROOMI ◽  
TATIANA KALINOVSKY ◽  
NUSRATH W. ROOMI ◽  
ALEKSANDRA NIEDZWIECKI ◽  
MATTHIAS RATH

Toxics ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 348
Author(s):  
Raúl Bonne Hernández ◽  
Nadja C. de Souza-Pinto ◽  
Jos Kleinjans ◽  
Marcel van Herwijnen ◽  
Jolanda Piepers ◽  
...  

Manganese (Mn) is an important element; yet acute and/or chronic exposure to this metal has been linked to neurotoxicity and neurodegenerative illnesses such as Parkinson’s disease and others via an unknown mechanism. To better understand it, we exposed a human neuroblastoma cell model (SH-SY5Y) to two Mn chemical species, MnCl2 and Citrate of Mn(II) (0–2000 µM), followed by a cell viability assay, transcriptomics, and bioinformatics. Even though these cells have been chemically and genetically modified, which may limit the significance of our findings, we discovered that by using RA-differentiated cells instead of undifferentiated SH-SY5Y cell line, both chemical species induce a similar toxicity, potentially governed by disruption of protein metabolism, with some differences. The MnCl2 altered amino acid metabolism, which affects RNA metabolism and protein synthesis. Citrate of Mn(II), however, inhibited the E3 ubiquitin ligases–target protein degradation pathway, which can lead to the buildup of damaged/unfolded proteins, consistent with histone modification. Finally, we discovered that Mn(II)-induced cytotoxicity in RA-SH-SY5Y cells shared 84 percent of the pathways involved in neurodegenerative diseases.


2021 ◽  
Vol 14 (11) ◽  
pp. 20-29
Author(s):  
Mozhdeh Hajimohammadjafar tehrania ◽  
Mahsa Ale-Ebrahim ◽  
Mojtaba Falahati ◽  
Shahram Zarabiyan ◽  
◽  
...  

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