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Published on: December 27, 2013
Upconversion-Mediated Optogenetics for the Treatment of Surgery-Induced Postoperative Neurocognitive Dysfunction
Linan Zhang1, Yilin Liu2, Gangjian Luo1
1Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, No. 600, Tianhe Road, Guangzhou 510635, China.
Abstract:
Perioperative neurocognitive disorder (PND) is a common complication in surgical patients. While many interventions to prevent PND have been studied, the availability of treatment methods is limited. Thus, it is crucial to delve into the mechanisms of PND, pinpoint therapeutic targets, and develop effective treatment approaches. In this study, reduced dorsal tenia tecta (DTT) neuronal activity was found to be associated with tibial fracture surgery-induced PND, indicating that a neuronal excitation-inhibition (E-I) imbalance could contribute to PND. Optogenetics in the DTT brain region was conducted using upconversion nanoparticles (UCNPs) with the ability to convert 808 nm near-infrared light to visible wavelengths, which triggered the activation of excitatory neurons with minimal damage in the DTT brain region, thus improving cognitive impairment symptoms in the PND model. Moreover, this noninvasive intervention to modulate E-I imbalance showed a positive influence on mouse behavior in the Morris water maze test, which demonstrates that UCNP-mediated optogenetics is a promising tool for the treatment of neurological imbalance disorders.
Insights
Perioperative neurocognitive disorder (PND) treatment is limited. This study shows optogenetics targeting dorsal tenia tecta (DTT) neuronal activity can improve PND symptoms by restoring brain excitation-inhibition balance.
Area of Science:
- Neuroscience
- Biomedical Engineering
- Surgical Research
Background:
- Perioperative neurocognitive disorder (PND) is a frequent complication following surgery, with limited effective treatment options.
- Understanding the underlying mechanisms of PND is critical for developing targeted therapies.
- Neuronal excitation-inhibition (E-I) imbalance is a potential contributor to PND.
Purpose of the Study:
- To investigate the role of dorsal tenia tecta (DTT) neuronal activity in PND.
- To explore UCNP-mediated optogenetics as a therapeutic strategy for PND.
- To assess the efficacy of modulating E-I balance in a PND mouse model.
Main Methods:
- Reduced DTT neuronal activity was identified as a correlate of tibial fracture surgery-induced PND.
- Optogenetics utilizing upconversion nanoparticles (UCNPs) were employed in the DTT region.
- UCNPs converted near-infrared light to visible wavelengths to activate excitatory neurons noninvasively.
Main Results:
- UCNP-mediated optogenetics successfully activated DTT excitatory neurons with minimal damage.
- This intervention improved cognitive impairment symptoms in the PND mouse model.
- The noninvasive approach positively influenced mouse behavior in the Morris water maze test.
Conclusions:
- Reduced DTT neuronal activity and subsequent E-I imbalance contribute to PND.
- UCNP-mediated optogenetics offers a promising, noninvasive method for treating neurological imbalance disorders.
- This approach represents a potential therapeutic avenue for PND and related conditions.
