» Articles » PMID: 30944722

7,8-Dihydroxyflavone Protects Nigrostriatal Dopaminergic Neurons from Rotenone-Induced Neurotoxicity in Rodents

Overview
Journal Parkinsons Dis
Publisher Wiley
Date 2019 Apr 5
PMID 30944722
Citations 14
Authors
Affiliations
Soon will be listed here.
Abstract

7,8-Dihydroxyflavone (7,8-DHF) is thought to be a promising therapeutic agent for various neurodegenerative diseases. The major purpose of this study was to investigate the neuroprotective effects of 7,8-DHF on the rotenone-induced motor deficit of Parkinson's disease. Nine-month-old rats were treated with rotenone (2 mg/kg/day, i.h.) for 5 weeks to establish the animal model of Parkinson's disease (PD), and 7,8-DHF (5 mg/kg, i.p.) was administrated daily throughout the whole period of rotenone injection. Five weeks later, an open field test was used to assess the motor ability of the animals. TH immunostaining was performed to evaluate rotenone-induced neurotoxicity on substantia nigra (SN) dopaminergic neurons and the DA terminals in the striatum. Western blot analyses were used to examine the expressions of TH, BDNF/TrkB signaling cascades, phospho--synuclein (Ser129), -synuclein, and phospho-tau (Ser396) in SN. The results revealed that treatment with 7,8-DHF improved PD model's behavioral performance and reduced dopaminergic neuron loss in the SN and striatum, associated with the activation of TrkB receptors and its signaling cascades, and reduced -MAPK, --synuclein, and -tau. Collectively, these results indicated that 7,8-DHF displayed prominent neuroprotective properties, providing a promising therapeutic strategy for PD treatment.

Citing Articles

Neuroprotective Effect of Maresin-1 in Rotenone-Induced Parkinson's Disease in Rats: The Putative Role of the JAK/STAT Pathway.

Khodir S, Sweed E, Faried M, Abo Elkhair D, Khalil M, Afifi K Neurochem Res. 2024; 50(1):30.

PMID: 39576344 PMC: 11584474. DOI: 10.1007/s11064-024-04282-x.


TrkB-mediated neuroprotection in female hippocampal neurons is autonomous, estrogen receptor alpha-dependent, and eliminated by testosterone: a proposed model for sex differences in neonatal hippocampal neuronal injury.

Chanana V, Zafer D, Kintner D, Chandrashekhar J, Eickhoff J, Ferrazzano P Biol Sex Differ. 2024; 15(1):30.

PMID: 38566248 PMC: 10988865. DOI: 10.1186/s13293-024-00596-1.


Invited Perspective: Challenging the Dogma of Lead Neurotoxicity.

Guilarte T Environ Health Perspect. 2023; 131(8):81306.

PMID: 37639478 PMC: 10461787. DOI: 10.1289/EHP13184.


7,8-dihydroxyflavone enhances long-term spatial memory and alters brain volume in wildtype mice.

Rawlings-Mortimer F, Lazari A, Tisca C, Tachrount M, Martins-Bach A, Miller K Front Syst Neurosci. 2023; 17:1134594.

PMID: 37008453 PMC: 10057119. DOI: 10.3389/fnsys.2023.1134594.


Treating Parkinson's Disease via Activation of BDNF/TrkB Signaling Pathways and Inhibition of Delta-Secretase.

Kang S, Wu Z, Liu X, Edgington-Mitchell L, Ye K Neurotherapeutics. 2022; 19(4):1283-1297.

PMID: 35595958 PMC: 9587159. DOI: 10.1007/s13311-022-01248-1.


References
1.
Parain K, Murer M, Yan Q, Faucheux B, Agid Y, Hirsch E . Reduced expression of brain-derived neurotrophic factor protein in Parkinson's disease substantia nigra. Neuroreport. 1999; 10(3):557-61. DOI: 10.1097/00001756-199902250-00021. View

2.
Seo S, Chong S, Lee S, Sung J, Ahn Y, Chung K . Zn2+-induced ERK activation mediated by reactive oxygen species causes cell death in differentiated PC12 cells. J Neurochem. 2001; 78(3):600-10. DOI: 10.1046/j.1471-4159.2001.00438.x. View

3.
Huang E, Reichardt L . Neurotrophins: roles in neuronal development and function. Annu Rev Neurosci. 2001; 24:677-736. PMC: 2758233. DOI: 10.1146/annurev.neuro.24.1.677. View

4.
Adachi T, Kar S, Wang M, Carr B . Transient and sustained ERK phosphorylation and nuclear translocation in growth control. J Cell Physiol. 2002; 192(2):151-9. DOI: 10.1002/jcp.10124. View

5.
Thoenen H, Sendtner M . Neurotrophins: from enthusiastic expectations through sobering experiences to rational therapeutic approaches. Nat Neurosci. 2002; 5 Suppl:1046-50. DOI: 10.1038/nn938. View