N‑Acetylcysteine-Capped TLQP21-Containing Au Nanocages Alleviate Depression in Mice
Meng Shi, Xiangyu Li, Zhen Fan, Yi Wang, Congcong Li, Yuanmeng Ning, Yizhao Ma, Min Sun, Xiaohuan Xia, Jianzhong Du, Jialin C. Zheng
TL;DR
A new nanoparticle treatment using N-acetylcysteine and TLQP21 reduces depression-like behaviors and brain inflammation in mice.
Contribution
A novel antioxidant Au nanocage delivers TLQP21 to target oxidative stress and microglial inflammation in depression.
Findings
TNNC administration reduced MDD-like behaviors in CUMS-exposed mice.
TLQP21 inhibited microglial activation and synaptic pruning via C1qR and C3aR1.
TNNC effectively relieved oxidative stress in the brain.
Abstract
Major depressive disorder (MDD) is the most prevalent neuropsychiatric disorder globally. Promising therapies for MDD are urgently needed due to the limited effectiveness, delayed efficacy, and non-negligible side effects of current treatments. Oxidative stress and neuroinflammation have been recognized as key contributors to MDD. Here, we developed an antioxidant N-acetylcysteine (NAC)-capped Au nanocage (TNNC) that entrapped VGF-derived peptide TLQP21 with neuro-immunomodulatory effects. Once internalized by cells suffering from oxidative stress, NAC was consumed, and TLQP21 was released from TNNC. TNNC administration alleviated MDD-like behaviors of the chronic unpredictable mild stress (CUMS)-exposed mice and effectively relieved oxidative stress in the brains. Moreover, TLQP21 in TNNC inhibits the activation, excessive synaptic pruning, and inflammatory responses of microglia…
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Taxonomy
TopicsTryptophan and brain disorders · Neuroinflammation and Neurodegeneration Mechanisms · Adenosine and Purinergic Signaling