Xianwen Zhang, Fang Yan, Xiong Jie He, Yali Chen, Rou Gu, Xianghuan Dong, Yonghang Wei, Liping Bai, Jie Bai
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引用次数: 0
Abstract
Aims: Parkinson's disease (PD) is characterized by dopaminergic (DAergic) neuron degeneration in the substantia nigra pars compacta (SNpc). Thioredoxin-1 (Trx-1) is a redox protein that protects neurons from various injuries. Our study revealed that Trx-1 overexpression improved the learning and memory impairments induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). However, the role of the specific transmission of signals from the SNpc to the hippocampus regulated by Trx-1 in cognition deficits associated with PD is still unknown. Results: We observed that Trx-1 downregulation in the SNpc aggravated cognitive dysfunction induced by MPTP. Importantly, we observed that the SNpc directly projects to the hippocampus. We found that the loss of DAergic neurons in the SNpc induced by MPTP resulted in a decrease in dopamine D1 receptor (D1R) expression in the hippocampus, which was promoted by Trx-1 downregulation in the SNpc. The levels of phosphorylated extracellular signal-regulated kinase (p-ERK1/2), phosphorylated cAMP-response element binding protein (p-CREB), brain-derived neurotrophic factor (BDNF), and postsynaptic density protein 95 (PSD95) in the hippocampus were decreased by MPTP and further decreased by Trx-1 downregulation in the SNpc. Finally, the number of synapses in the hippocampus was decreased by MPTP in the hippocampus and further reduced by Trx-1 downregulation in the SNpc. Innovation: Trx-1 downregulation accelerated the loss of DAergic neurons in the SNpc, leading to a decrease in the number dopaminergic projections to the hippocampus, subsequently inhibiting the D1R-ERK1/2-CREB-BDNF pathway in the hippocampus, and ultimately impairing hippocampus-dependent cognition. Conclusions: These results indicate that a decrease in Trx-1 level in the SNpc plays a critical regulatory role in cognitive dysfunction in individuals with PD by decreasing the hippocampal D1R signaling pathway. Antioxid. Redox Signal. 00, 000-000.
期刊介绍:
Antioxidants & Redox Signaling (ARS) is the leading peer-reviewed journal dedicated to understanding the vital impact of oxygen and oxidation-reduction (redox) processes on human health and disease. The Journal explores key issues in genetic, pharmaceutical, and nutritional redox-based therapeutics. Cutting-edge research focuses on structural biology, stem cells, regenerative medicine, epigenetics, imaging, clinical outcomes, and preventive and therapeutic nutrition, among other areas.
ARS has expanded to create two unique foci within one journal: ARS Discoveries and ARS Therapeutics. ARS Discoveries (24 issues) publishes the highest-caliber breakthroughs in basic and applied research. ARS Therapeutics (12 issues) is the first publication of its kind that will help enhance the entire field of redox biology by showcasing the potential of redox sciences to change health outcomes.
ARS coverage includes:
-ROS/RNS as messengers
-Gaseous signal transducers
-Hypoxia and tissue oxygenation
-microRNA
-Prokaryotic systems
-Lessons from plant biology