7, 8-Dihydroxyflavone Ameliorates Depression-Like Behaviors in Mice Induced by Toxoplasma gondii via the BDNF-TrkB
Wen-Qian Shi1,2, Haiqiong Yu3, Shao-Yuan Bai1
1Institute of Comparative Medicine, College of Veterinary Medicine, Yangzhou University, and Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, and Jiangsu Key Laboratory of Zoonosis, Yangzhou, People's Republic of China.
Abstract:
Chronic toxoplasmosis has been increasingly associated with behavior disorders, including depression-like behaviors, while the underlying mechanisms remain poorly understood. In this study, we demonstrated that chronic toxoplasmosis induced depression-like behaviors in mice, which were observed together with neuroinflammation, neuronal injury, and suppression of the BDNF-TrkB pathway. Treatment with the TrkB agonist 7,8-DHF alleviated these behavioral deficits by restoring BDNF-TrkB signaling, preserving neuronal function, and reducing neuroinflammation through inhibition of NF-κB and MAPK pathways. Additionally, 7,8-DHF also reduced astrocyte overactivation and protected blood-brain barrier structure integrity. These findings highlight that disruption of BDNF-TrkB signaling contributes to T. gondii-induced behavioral abnormalities and that targeting this pathway may represent a promising therapeutic strategy against neuroinflammation and neuronal damage associated with chronic infection.
Insights
Chronic toxoplasmosis causes depression-like behaviors by disrupting brain pathways. A TrkB agonist, 7,8-DHF, reversed these effects, suggesting a new therapeutic target for infection-related neurological disorders.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Chronic toxoplasmosis is linked to behavioral disorders, but mechanisms are unclear.
- Depression-like behaviors are observed in toxoplasmosis, associated with neuroinflammation and neuronal damage.
- The brain-derived neurotrophic factor (BDNF)-Tropomyosin receptor kinase B (TrkB) pathway's role is poorly understood in this context.
Purpose of the Study:
- To investigate the mechanisms underlying depression-like behaviors in chronic toxoplasmosis.
- To evaluate the therapeutic potential of targeting the BDNF-TrkB pathway.
- To assess the effects of 7,8-DHF on neuroinflammation and neuronal integrity.
Main Methods:
- Induction of chronic toxoplasmosis in a mouse model.
- Behavioral tests to assess depression-like phenotypes.
- Analysis of neuroinflammation markers (NF-κB, MAPK), neuronal injury, and BDNF-TrkB signaling.
- Assessment of astrocyte activation and blood-brain barrier integrity.
- Treatment with the TrkB agonist 7,8-DHF.
Main Results:
- Chronic toxoplasmosis induced depression-like behaviors, neuroinflammation, and neuronal injury in mice.
- BDNF-TrkB signaling was suppressed in infected mice.
- Treatment with 7,8-DHF ameliorated behavioral deficits.
- 7,8-DHF restored BDNF-TrkB signaling, reduced neuroinflammation (inhibiting NF-κB and MAPK), and protected neuronal function.
- 7,8-DHF also reduced astrocyte overactivation and maintained blood-brain barrier integrity.
Conclusions:
- Disruption of BDNF-TrkB signaling is a key mechanism in Toxoplasma gondii-induced behavioral abnormalities.
- Targeting the BDNF-TrkB pathway with agonists like 7,8-DHF shows therapeutic promise.
- This approach may mitigate neuroinflammation and neuronal damage in chronic toxoplasmosis.
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