Zinc (Zn) and adipose-derived mesenchymal stem cells (AD-MSCs) on MPTP-induced Parkinson’s disease model: A comparative evaluation of behavioral and immunohistochemical results

Parkinson’s disease (PD) is characterized by the loss of dopaminergic neurons and sustained neuroinflammation due to microglial activation. Adipose tissue-derived mesenchymal stem cells (AD-MSCs) secrete neuroprotective factors to prevent neuronal damage. Furthermore, Zn regulates stem cell prolifer...

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Veröffentlicht in:Neurotoxicology (Park Forest South) 2023-07, Vol.97, p.1-11
Hauptverfasser: Yildirim, Sendegul, Oylumlu, Ece, Ozkan, Ayse, Sinen, Osman, Bulbul, Mehmet, Goksu, Ethem Taner, Ertosun, Mustafa Gokhan, Tanriover, Gamze
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Sprache:eng
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Zusammenfassung:Parkinson’s disease (PD) is characterized by the loss of dopaminergic neurons and sustained neuroinflammation due to microglial activation. Adipose tissue-derived mesenchymal stem cells (AD-MSCs) secrete neuroprotective factors to prevent neuronal damage. Furthermore, Zn regulates stem cell proliferation and differentiation and has immunomodulatory functions. Our in vivo study aimed to investigate whether Zn affects the activities of AD-MSCs in the MPTP-induced mouse model. Male C57BL/6 mice were randomly divided into six groups (n = 6): Control, Zn, PD, PD+Zn, PD+ (AD-MSC), PD+ (AD-MSC)+Zn. MPTP toxin (20 mg/kg) was dissolved in saline and intraperitoneally injected into experimental groups for two days with 12 h intervals. On the 3rd day, AD-MSCs were given to the right lateral ventricle of the PD+ (AD-MSC) and PD+ (AD-MSC)+Zn groups by stereotaxic surgery. Then, ZnSO4H2O was administered intraperitoneally for 4 days at 2 mg/kg. Seven days post MPTP injection, the motor activities of the mouse were evaluated. Then immunohistochemical analyzes were performed in SNpc. Our results showed that motor activity was lower in Group PD. AD-MSC and Zn administration have improved this impairment. MPTP caused a decrease in TH and BDNF expressions in dopaminergic neurons in Group PD. However, TH and BDNF expressions were more intense in the other groups. MCP-1, TGF-β, and IL-10 expressions increased in administered groups compared to the Group PD. The present study indicates that Zn’s individual and combined administration with AD-MSCs reduces neuronal damage in the MPTP-induced mouse model. In addition, anti-inflammatory responses that emerge with Zn and AD-MSCs may have a neuroprotective effect. [Display omitted] •In experimental animal models, MPTP is a neurotoxic agent that mimics PD-like symptoms such as bradykinesia, locomotor activity impairment, and tremor.•Adipose tissue-derived mesenchymal stem cells (AD-MSCs) secrete neuroprotective factors to prevent neuronal damage.•Zn regulates stem cell proliferation and differentiation and has immunomodulatory functions.•Zn and AD-MSC administration attenuates MPTP-induced motor impairments and dopaminergic neuron damage.•Zn and AD-MSC administration increases MPTP-induced anti-inflammatory response.
ISSN:0161-813X
1872-9711
DOI:10.1016/j.neuro.2023.05.002