Exploring the interplay of chronic toxoplasmosis and NMDAR dysfunction: Insights into schizophrenia-like behaviors and therapeutic potential.
Seyedeh Mina Masoumi, Mohammad Reza Youssefi, Seyed Shapoor Reza Shojaei
Open veterinary journal July 1, 2024 DOI: 10.5455/OVJ.2024.v14.i7.13 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Controlled laboratory experiment Peer reviewed |
|---|---|
| Sample size | 60 |
| Population | Male BALB/c mice |
| Interventions | Toxoplasma gondii infection ketamine sulfadiazine-trimethoprim |
| Duration | 10 weeks post-infection |
| Topics | Ketamine |
| Keywords | Antioxidant status Behavioral alterations Toxoplasma gondii Parasitology Mental health Psychopharmacology Schizophrenia |
| Citations | 2 |
| Key findings | Both Toxoplasma gondii infection and ketamine treatment induce schizophrenia-like behavioral changes, reduce brain antioxidant levels, increase lipid peroxidation, and downregulate NMDA receptor subunits NR1 and NR2A in mice, with sulfadiazine-trimethoprim partially reversing the receptor changes but not all behavioral alterations. |
Abstract
Chronic toxoplasmosis has been strongly implicated in the development of psychosis and schizophrenia. Additionally, the understanding of schizophrenia has been significantly reshaped by insights into N-methyl-D-aspartate receptor (NMDAR) hypofunction. This study aimed to compare the behavioral, antioxidant, and NMDAR changes in mice subjected to Toxoplasma gondii infection and those treated with ketamine to induce schizophrenia-like symptoms. Sixty male BALB/c mice were divided into six groups: toxoplasmosis (TOXO) (infected), ketamine-induced schizophrenia (KET), TOXO+KET, TOXO+sulfadiazine-trimethoprim treatment (SDT), TOXO+KET+SDT, and control (CON) (uninfected). After 10 weeks post-infection, behavioral tests were conducted, brain antioxidant status and lipid peroxidation were analyzed, and NMDA-NR1/NR2A expressions were assessed. TOXO and KET induced distinct behaviors: hyperlocomotion, anxiety, and memory impairment. Antioxidant enzyme levels decreased, and lipid peroxidation increased in TOXO and schizophrenic mice brains. NMDAR downregulation, especially NR-1 and NR2A, was evident due to T. gondii and ketamine. Sulfadiazine-trimethoprim ameliorated NMDAR downregulation, but not all of the behavioral alterations. Further studies are needed to elucidate specific NMDAR subunit roles in toxoplasmosis-induced pathophysiology, offering potential therapeutic insights. This investigation highlights the intricate relationship between chronic toxoplasmosis, NMDAR dysfunction, and schizophrenia-like behaviors. Insights gained could pave the way for innovative interventions targeting both cognitive and neurological impairments associated with these conditions.
Comparable studies
Other preclinical and animal studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats | 2010 | Observational study | |
| Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats | 1997 | Dose-response study with microdialysis and behavioral testing | |
| NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice | 2016 | Preclinical study | |
| The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats | 1983 | Experimental study | |
| R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice | 2015 | Experimental study |
Citations in the library
Cites 3
- Prevention and reversal of ketamine-induced schizophrenia related behavior by minocycline in mice: Possible involvement of antioxidant and nitrergic pathways Journal of Psychopharmacology September 17, 2013
- Neuroprotective effects of curcumin-loaded nanophytosome on ketamine-induced schizophrenia-like behaviors and oxidative damage in male mice. Neuroscience Letters September 15, 2021
- NMDA receptor and schizophrenia: a brief history. Schizophrenia Bulletin September 2012