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

Mahmoudvand, Hossein; Sheibani, Vahid; Shojaee, Saeideh; Mirbadie, Seyed Reza; Keshavarz, Hossein; Esmaeelpour, Khadijeh; Keyhani, Ali Reza; Ziaali, Naser

doi:10.1645/16-28

Cited by 51 publications

(38 citation statements)

References 30 publications

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“…Moreover, cysts of T. gondii in specific forebrain areas of rats had been attributed to attenuation of predator odor aversion and changes in anxiety-related behavior [6]. Association between T. gondii and anxiety and cognitive disorders has also been reported [8,9].…”

Section: Introductionmentioning

confidence: 99%

Angiostrongylus cantonensis causes cognitive impairments in heavily infected BALB/c and C57BL/6 mice

Jhan

Lai

Chang

et al. 2020

Preprint

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Background: Parasitic infections may cause significant effects on behavior, learning, and memory of the hosts. In the brain of mice heavily infected with Angiostrongylus cantonensis, severe damages have been observed in the hippocampus. This component has been considered to have associations with spatial learning and memory in human and vertebrates. This study was designed to determine the impairments in behavior, learning, and memory in BALB/c and C57BL/6 mice heavily infected with the parasite. Methods: Each mouse was inoculated with 50 third-stage larvae of A. cantonensis. After infection, daily changes in weight and dietary consumption, worm recoveries and survival rates were determined. The forced swimming test, open field test, and Morris water maze test were employed to evaluate depression- and anxiety-like behavior as well as impairments in spatial learning and memory, respectively. In addition, in the two strains of mice were also determined. Results: The worm recovery rate in the BALB/c mice was significantly lower than that of C57BL/6 mice since day 14 post-infection. The survival rate in infected BALB/c mice decreased to 0% by day 25 whereas those with swim-training survived three more days. On day 42, the C57BL/6 mice had a survival rate of 85.7% in the swimming group and 70% in the non-swimming group. Significant differences were found in weight between infected and non-infected BALB/c and C57BL/6 mice since day 13 and day 12, respectively with corresponding changes in the dietary consumption. Depression-like behavior was found in the infected BALB/c mice but not in C57BL/6 mice. However, anxiety-like behavior was found to occur only in C57BL/6 mice. Impaired spatial learning and memory were also found in the two strains of mice occurred since day 14 post-infection. Conclusions: Results of this study indicate that A. cantonensis causes depression, anxiety, and impairments in spatial learning and memory in heavily infected mice. Moreover, significantly higher severity was observed in the Th-2 dominant BALB/c mice. Keywords: Angiostrongyliasis cantonensis, mice, behavior, learning, memory, forced swimming test, open field test, Morris water maze test

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Section: Introductionmentioning

confidence: 99%

Angiostrongylus cantonensis causes cognitive impairments in heavily infected BALB/c and C57BL/6 mice

Jhan

Lai

Chang

et al. 2020

Preprint

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“…Also, our previous research results show that GRA15 can induce mouse macrophages to M1 in vitro [30,31] . As is known, the relative intensity of virulence in some T. gondii stains prevalent in the world is compared as following: RH > TgCtwh3 > TgCtwh6 > Pru [32] . But the relationship between TgCtwh6 and cognitive behavior has not been studied so far.…”

Section: Introductionmentioning

confidence: 99%

Toxoplasma gondii Chinese 1 Genotype Wh6 Strain Causes Mice Abnormal Cognitive Behavior through Affecting Hippocampal Neurons

Tao

Cui

Liu

et al. 2020

Preprint

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BackgroundChronic Toxoplasma gondii (T. gondii) infection evokes abnormal cognitive behavior of the host. Recent studies suggest that the polarization of microglia to the phenotype of classically activated macrophage (M1) and the deposition of beta-amyloid (Aβ) may be induced in brain of mice chronically infected with T. gondii. However, so far, there is no definite explanation for the relationship mechanism underlying the above between microglia polarization, Aβ deposition and T. gondii. Our previous investigations indicated that in vitro T. gondii type Ⅱ strain dense granule protein 15 (GRA15Ⅱ), one of the genotype-associated effectors of T. gondii Ⅱ strain may induce mouse macrophage to M1. While T. gondii type Ⅰ/Ⅲ strain rhoptry protein 16 (ROP16Ⅰ/Ⅲ) can drive the mouse macrophage to the phenotype of alternatively activated macrophage (M2). Unlike the archetypal strains of types Ⅰ, Ⅱ, and Ⅲ, T. gondii Chinese 1 genotype Wh6 strain (TgCtwh6) possesses both GRA15Ⅱ and ROP16Ⅰ/Ⅲ proteins, indicating the unique pathogenesis of Toxoplasma-related cognitive behavioral abnormalities.MethodsIn this study, we constructed mice model of cognitive behavioral abnormalities through chronic infection of TgCtwh6 via the oral route, and used mouse hippocampal neuronal cell line (HT22) and mouse microglial cell line (BV2) infected with TgCtwh6 in co-culture system to explore the mechanism with which TgCtwh6 infection induced mouse abnormal cognitive behavior. The immunohistochemistry, immunofluorescence, western blotting, cell culture assays, as well as an array of mouse behavior tests were adopted in the research.ResultsIn our research, the infected group showed abnormal cognitive behavior in the water maze and open field experiments in comparison with the control group. Further study showed that the number of synapses and hippocampal neurons decreased and the expression of Aβ increased in brain. In vitro, our research indicated that TgCtwh6 infection could not only directly lead to the HT22 apoptosis but also directly induce BV2 activation to M1 possibly through Notch pathway. Activated BV2 secreted pro-inflammatory factors resulting in HT22 apoptosis indirectly in transwell device. Meanwhile, our reseach demonstrated that TgCtwh6 infection caused a notable expression of β-secretase 1 (BACE1)、amyloid precursor protein (APP) and Aβ in HT22 through NF-κB signaling. Furthmore, BV2 activated by TgCtwh6 infection produced pro-inflammatory factors, such as IL-6, TNF-α and iNOS, which promoted HT22 to express APP in co-culture system. In all, our results suggested that TgCtwh6 gave rise to mouse abnormal cognitive behavior due to hippocampal neuronal apoptosis and Aβ deposition driven by indirect and indirect TgCtwh6 infection to hippocampal neuron. In this pathogenic process, microglia activation played an important role in mediating hippocampal neuronal apoptosis and Aβ deposition.ConclusionsThis study demonstrates TgCtwh6 infection can cause mice to develop AD-like symptoms and give rise to hippocampal neuronal apoptosis and Aβ deposition. Besides, microglia activation played an functional role in the pathological development.

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“…Moreover, cysts of T. gondii in speci c forebrain areas of rats had been attributed to attenuation of predator odor aversion and changes in anxiety-related behavior [6]. Association between T. gondii and anxiety and cognitive disorders has also been reported [8,9].…”

Section: Introductionmentioning

confidence: 99%

Angiostrongylus cantonensis causes cognitive impairments in heavily infected BALB/c and C57BL/6 mice

Jhan

Lai

Chang

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Parasitic infections may cause significant effects on behavior, learning, and memory of the hosts. In the brain of mice heavily infected with Angiostrongylus cantonensis, severe damages have been observed in the hippocampus. This component has been considered to have associations with spatial learning and memory in human and vertebrates. This study was designed to determine the impairments in behavior, learning, and memory in BALB/c and C57BL/6 mice heavily infected with the parasite.Methods: Each mouse was inoculated with 50 third-stage larvae of A. cantonensis. After infection, daily changes in weight and dietary consumption, worm recoveries and survival rates were determined. The forced swimming test, open field test, and Morris water maze test were employed to evaluate depression- and anxiety-like behavior as well as impairments in spatial learning and memory, respectively. In addition, in the two strains of mice were also determined.Results: The worm recovery rate in the BALB/c mice was significantly lower than that of C57BL/6 mice since day 14 post-infection. The survival rate in infected BALB/c mice decreased to 0% by day 25 whereas those with swim-training survived three more days. On day 42, the C57BL/6 mice had a survival rate of 85.7% in the swimming group and 70% in the non-swimming group. Significant differences were found in weight between infected and non-infected BALB/c and C57BL/6 mice since day 13 and day 12, respectively with corresponding changes in the dietary consumption. Depression-like behavior was found in the infected BALB/c mice but not in C57BL/6 mice. However, anxiety-like behavior was found to occur only in C57BL/6 mice. Impaired spatial learning and memory were also found in the two strains of mice occurred since day 14 post-infection.Conclusions: Results of this study indicate that A. cantonensis causes depression, anxiety, and impairments in spatial learning and memory in heavily infected mice. Moreover, significantly higher severity was observed in the Th-2 dominant BALB/c mice.

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Toxoplasma gondiiInfection Potentiates Cognitive Impairments of Alzheimer's Disease in the BALB/c Mice

Cited by 51 publications

References 30 publications

Angiostrongylus cantonensis causes cognitive impairments in heavily infected BALB/c and C57BL/6 mice

Angiostrongylus cantonensis causes cognitive impairments in heavily infected BALB/c and C57BL/6 mice

Toxoplasma gondii Chinese 1 Genotype Wh6 Strain Causes Mice Abnormal Cognitive Behavior through Affecting Hippocampal Neurons

Angiostrongylus cantonensis causes cognitive impairments in heavily infected BALB/c and C57BL/6 mice

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Toxoplasma gondiiInfection Potentiates Cognitive Impairments of Alzheimer's Disease in the BALB/c Mice

Cited by 51 publications

References 30 publications

Angiostrongylus cantonensis causes cognitive impairments in heavily infected BALB/c and C57BL/6 mice

Angiostrongylus cantonensis causes cognitive impairments in heavily infected BALB/c and C57BL/6 mice

Toxoplasma gondii&nbsp;Chinese 1 Genotype Wh6 Strain Causes Mice Abnormal Cognitive Behavior through Affecting Hippocampal Neurons

Angiostrongylus cantonensis causes cognitive impairments in heavily infected BALB/c and C57BL/6 mice

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Toxoplasma gondii Chinese 1 Genotype Wh6 Strain Causes Mice Abnormal Cognitive Behavior through Affecting Hippocampal Neurons