Toxoplasma gondii Infection Potentiates Cognitive Impairments of Alzheimer's Disease in the BALB/c Mice.

This study tests the hypothesis that in chronic Toxoplasma gondii infection communication among immune cells promotes neuroinflammation through cytokine networks and potentiate cognitive impairments in BALB/c mice with Alzheimer's disease (AD). The animal model of Toxoplasma infection was established by the intraperitoneal inoculation of 20-25 tissue cysts from the Tehran strain of T. gondii . We injected amyloid-beta 1-42 peptide (Aß1-42, 1 and 2 µl) into the hippocampus of BALB/c mice to establish an animal model of AD. The behavioral experiments such as spatial learning and memory were performed using the Morris water maze test. The mRNA levels of TNF-α, IL-1ß, IFN-γ, and inducible nitric oxide synthase (iNOS) were examined by real-time PCR. We found that T. gondii infection caused AD-like symptoms and impaired learning and memory functions of the infected BALB/c mice. We also found that in Toxoplasma infection + Aß1-42 (1 µl) group, T. gondii infection could potentiate AD in infected mice receiving subdoses of Aß1-42 (1 µl) and caused considerable impairment in learning and memory functions similar to AD group. Comparison of the results demonstrated that mRNA levels of IL-1ß, TNF-α, IFN-γ, and iNOS significantly (P < 0.001) increased in T. gondii + Aß1-42 (1 µl) in comparison with the other tested groups. The obtained results showed that chronic T. gondii infection communication among immune cells promotes neuroinflammation through cytokine networks and induces pathological progression of AD in the mice brain, whereas the presence of neuroanatomical Toxoplasma tissue cysts in the brain could also affect the behavioral functions in T. gondii -infected mice.

Acetylcholinesterase Inhibitor Improves Learning and Memory Impairment Induced by Toxoplasma gondii Infection.

BACKGROUND: Here, we established the mouse models of chronic toxoplasmosis by T. gondii Tehran strain to provide a good understanding about defining the possible association between T. gondii exposure and learning and memory impairments. Moreover, as secondary objective of the present study, we hypothesized whether administration of an acetylcholinesterase (AChE) inhibitor could reduce learning and memory impairments induced by T. gondii infection. METHODS: Twenty-four male BALB/c mice were used to establishment of latent toxoplasmosis. The animal model of Toxoplasma infection was established by the intraperitoneal inoculation of 20-25 tissue cysts from Tehran strain of T. gondii. Donepezil (2 mg/kg) an AChE inhibitor to treat Alzheimer disease was injected intraperitoneally once a day for two weeks starting from post-infection day 90. Morris water maze (MWM) task was used to assay spatial learning and short term spatial memory in all groups. One-way ANOVA with Tukey's post-hoc test was used to assess differences between experimental groups. P<0.05 was considered statistically significant. RESULTS: Toxoplasma infection impaired spatial leaning and short term spatial memory of the infected BALB/c mice, whereas donepezil, an AChE inhibitor, improved impairments induced by Toxoplasma infection. CONCLUSION: T. gondii infection through increasing AChE reduces the level of Acetylcholine (Ach) and consequently affects learning and memory activity in infected hosts, whereas, donepezil as an AChE inhibitor improves these impairments by restoring ACh levels at synapses of neurons in brain.

The compensatory effect of regular exercise on long-term memory impairment in sleep deprived female rats.

Previous studies have been shown that exercise can improve short-term spatial learning, memory and synaptic plasticity impairments in sleep deprived female rats. The aim of the present study was to investigate the effects of treadmill exercise on sleep deprivation (SD) induced impairment in hippocampal dependent long-term memory in female rats. Intact and ovariectomized female rats were used in the current study. Exercise protocol was 4 weeks treadmill running. Twenty four hour SD was induced by using multiple platform apparatus after learning phase. Spatial learning and long-term memory was examined by using the Morris Water Maze (MWM) test. Our results indicated that sleep deprivation impaired long term memory in the intact and ovariectomized female rats, regardless of reproductive status (p<0.05) and treadmill exercise compensated this impairment (p<0.05). In conclusion the results of the current study confirmed the negative effect of SD on cognitive functions and regular exercise seems to protect rats from these factors, however more investigations need to be done.