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Updated: Dec 23, 2025
3-D Imaging and Analysis of Neurons Infected In Vivo with Toxoplasma gondii
Published on: December 9, 2014
Cannabinoid receptors and the proconvulsant effect of toxoplasmosis in mice
Mohammad-Mahdi Ghanbari1, Marzieh Joneidi2, Bahere Kiani3
1Department of Physiology and Pharmacology, Pasteur Institute of Iran, Tehran, Iran; Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Abstract:
Toxoplasmosis is an infectious disease caused by the intracellular parasite Toxoplasma gondii that harms the brain and increases the risk of epilepsy acquisition. It is well known that cannabinoid (CB) signaling is activated following brain insults and protects the neurons from excitotoxicity and inflammation. We examined the role of CB neurotransmission in the proconvulsant effect of Toxoplasmosis in mice. Toxoplasmosis was established in mice by intraperitoneal injection of T. gondii cysts. The mice with acute and/or chronic Toxoplasma infection were pretreated (through intracerebroventricular injection) with CB1 and CB2 receptor agonists (ACEA and HU308) and antagonists (AM251 and AM630), as well as JZL184 (the irreversible inhibitor of mono acyl glycerol lipase, enzyme degrading the endogenous cannabinoid 2-Acyl glycerol). The seizure threshold was then measured by tail vein infusion of pentylenetetrazole. In healthy uninfected mice JZL184, ACEA, and AM630 increased the seizure threshold in a dose-dependent manner, whereas AM251 and HU308 showed dose-dependent proconvulsant effect. Mice with acute and/or chronic infection had a substantial lower seizure threshold than the uninfected mice. JZL 184, ACEA and AM630 inhibited proconvulsant effect of Toxoplasmosis, while AM251 and HU308 intensified proconvulsant effect of Toxoplasmosis. CB receptors play a role in proconvulsant effect of Toxoplasmosis in mice.
Insights
Toxoplasmosis infection lowers seizure threshold in mice. Cannabinoid (CB) signaling modulates this effect, with CB1 and CB2 receptor agonists showing protective roles against seizures.
Area of Science:
- Neuroscience
- Infectious Diseases
- Pharmacology
Background:
- Toxoplasmosis, caused by *Toxoplasma gondii*, is linked to neurological issues like epilepsy.
- Cannabinoid (CB) signaling is activated in brain injuries and offers neuroprotection.
- The role of CB neurotransmission in toxoplasmosis-induced seizures remains unclear.
Purpose of the Study:
- To investigate the involvement of CB receptors in the proconvulsant effects of toxoplasmosis in a mouse model.
- To determine how CB1 and CB2 receptor agonists and antagonists influence seizure thresholds during infection.
Main Methods:
- Mice were infected with *Toxoplasma gondii* to establish acute and/or chronic toxoplasmosis.
- Intracerebroventricular injections of CB1/CB2 agonists (ACEA, HU308) and antagonists (AM251, AM630), and MAGL inhibitor (JZL184) were administered.
- Seizure threshold was assessed using pentylenetetrazole-induced seizures.
Main Results:
- In uninfected mice, JZL184, ACEA, and AM630 increased seizure threshold, while AM251 and HU308 decreased it.
- Infected mice exhibited a significantly lower seizure threshold compared to controls.
- JZL184, ACEA, and AM630 attenuated the proconvulsant effect of toxoplasmosis, whereas AM251 and HU308 exacerbated it.
Conclusions:
- CB receptors play a significant role in modulating the proconvulsant effects associated with toxoplasmosis in mice.
- Targeting CB signaling pathways may offer therapeutic potential for managing epilepsy risk in toxoplasmosis.
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