Abstract
Neural stem/progenitor cells hold valuable potential for the treatment of neurodegenerative disorders. The modulation of intrinsic growth factor expression, such as neurotrophins and their receptors, is a necessary step in achieving neural stem cells (NSCs) therapy. The statins have recently been reported to provide both anti‑inflammatory and neuroprotective effects. In the developing and mature nervous systems, neurotrophic factors are known to impact neuronal growth and survival. In this study, we investigated for a positive effect of lovastatin on the expression of neurotrophins in the neonatal rat hippocampus‑derived NSCs. NSCs were isolated and cultured up to passage three. To confirm cellular identity, immunocytochemical evaluation and flow cytometry analysis were performed using specific antibodies. To determine the optimum concentration of lovastatin, the MTT assay was used. Neurotrophin expression was evaluated using quantitative real‑time reverse transcription‑polymerase chain reaction (RT‑qPCR). Flow cytometry results demonstrated that NSCs were positive for nestin, a marker for neural progenitor cells. An increase in cellular viability was observed with a 24 h exposure of lovastatin. Moreover, results showed an increase in mRNA expression for all neurotrophins compared to the control group. Taken together, the results of this study add to the growing body of literature on the neuroprotective effects of statins in neurological disorders. Lovastatin is a promising therapeutic agent for the treatment of neurodegenerative disorders.
Highlights
Neurotrophins are comprised of a small family of dimeric proteins, which assist in differentiation and survival of peripheral and central neurons
neural stem cells (NSCs) (105 cells/well) were suspended in DMEM/F12 supplemented with 2% B27, 20 ng/ml basic fibroblast growth factor (bFGF), 20 ng/ml epidermal growth factor (EGF) and 3% fetal bovine serum (FBS; Gibco; Thermo Fisher Scientific Inc., Waltham, MA, USA) for one week in 6‐well adherent plates coated with poly‐l‐lysine and cultured up to passage num‐
The results of the present study showed that lovas‐ tatin induced expression of neurotrophic factors in the treated NSCs as compared to the control group
Summary
Neurotrophins are comprised of a small family of dimeric proteins, which assist in differentiation and survival of peripheral and central neurons. Nerve growth factor (NGF), the first described member of the neu‐ rotrophin family, is best known for its trophic role in the prevention of programmed cell death in the neuron populations of the peripheral nervous system (Frade and Barde, 1998). Other members of the neurotrophin fam‐ ily, including ciliary neurotrophic factor (CNTF), neu‐ rotrophin‐3 (NT‐3), glial cell line–derived neurotroph‐ ic factor (GDNF), and neurotrophin‐4 (NT‐4), have been described with distinct trophic effects on differ‐ ent neuronal populations of the peripheral and central nervous system. Statins are 3‐hydroxy‐3‐methylglutaryl coenzyme A (HMG‐CoA) reductase inhibitors, which are used to treat dyslipidemia and reduce the risks asso‐
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