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Transcriptome and histopathological changes in mouse brain infected with Neospora caninum.

Nishimura M, Tanaka S, Ihara F, Muroi Y, Yamagishi J, Furuoka H, Suzuki Y, Nishikawa Y - Sci Rep (2015)

Bottom Line: A GOstat analysis predicted that the upregulated genes were involved in the host immune response.Genes whose expression correlated positively and negatively with parasite numbers were involved in the host immune response, and neuronal morphogenesis and lipid metabolic processes, respectively.These results suggest that changes in the gene expression profile associated with neuronal functions as well as immune responses can contribute to the pathogenesis in N. caninum-infected animals.

View Article: PubMed Central - PubMed

Affiliation: National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido, Japan.

ABSTRACT
Neospora caninum is a protozoan parasite that causes neurological disorders in dogs and cattle. It can cause nonsuppurative meningoencephalitis and a variety of neuronal symptoms are observed, particularly in dogs. However, the pathogenic mechanism, including the relationship between the parasite distribution and the clinical signs, is unclear. In this study, to understand the pathogenic mechanism of neosporosis, parasite distribution and lesions were assessed in the brain of mice infected with N. caninum (strain Nc-1). Host gene expression was also analyzed with RNA sequencing (RNA-Seq). The histopathological lesions in the frontal lobe and the medulla oblongata were significantly more severe in symptomatic mice than in asymptomatic mice, although no association between the severity of the lesions and parasite numbers was found. In infected mice, the expression of 772 mouse brain genes was upregulated. A GOstat analysis predicted that the upregulated genes were involved in the host immune response. Genes whose expression correlated positively and negatively with parasite numbers were involved in the host immune response, and neuronal morphogenesis and lipid metabolic processes, respectively. These results suggest that changes in the gene expression profile associated with neuronal functions as well as immune responses can contribute to the pathogenesis in N. caninum-infected animals.

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Related in: MedlinePlus

Immunohistochemical analysis of macrophages/microglia and iNOS in lesions of N. caninum-infected mouse brain.(A–C) Serial sections of N. caninum-infected mouse brain. (A and A′) HE staining. (A′) A high-magnification image showing focal necrosis with mononuclear cell infiltration and cuffing. (B and B′) Immunohistochemical analysis with anti-Iba1 antibody. Infiltration of activated macrophages/microglia was observed around the necrotic area. (C and C′) Immunohistochemical analysis with an anti-iNOS antibody. Expression of iNOS was detected in inflammatory cells around the necrotic areas.
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f3: Immunohistochemical analysis of macrophages/microglia and iNOS in lesions of N. caninum-infected mouse brain.(A–C) Serial sections of N. caninum-infected mouse brain. (A and A′) HE staining. (A′) A high-magnification image showing focal necrosis with mononuclear cell infiltration and cuffing. (B and B′) Immunohistochemical analysis with anti-Iba1 antibody. Infiltration of activated macrophages/microglia was observed around the necrotic area. (C and C′) Immunohistochemical analysis with an anti-iNOS antibody. Expression of iNOS was detected in inflammatory cells around the necrotic areas.

Mentions: Tachyzoites were found within some lesions, but no tissue cysts were found in the present study. Therefore, the tropism of tissue cysts was not determined histopathologically. We also investigated the distribution of the parasite in the brain with real-time PCR. The numbers of parasites for each area of the brain are shown in Figure 2F. A sporadically high parasite load was detected in the frontal lobe and periaqueductal gray of the symptomatic mice. However we could not evaluate the difference of parasite number among the areas statistically because of small sample number. No association between the parasite load and the severity of the lesions was found. In an immunohistochemical analysis, the infiltration of macrophages or microglia and the production of inducible nitric oxide synthase (iNOS) were predominantly observed in the necrotic and inflammatory lesions (See Figure 3).


Transcriptome and histopathological changes in mouse brain infected with Neospora caninum.

Nishimura M, Tanaka S, Ihara F, Muroi Y, Yamagishi J, Furuoka H, Suzuki Y, Nishikawa Y - Sci Rep (2015)

Immunohistochemical analysis of macrophages/microglia and iNOS in lesions of N. caninum-infected mouse brain.(A–C) Serial sections of N. caninum-infected mouse brain. (A and A′) HE staining. (A′) A high-magnification image showing focal necrosis with mononuclear cell infiltration and cuffing. (B and B′) Immunohistochemical analysis with anti-Iba1 antibody. Infiltration of activated macrophages/microglia was observed around the necrotic area. (C and C′) Immunohistochemical analysis with an anti-iNOS antibody. Expression of iNOS was detected in inflammatory cells around the necrotic areas.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4300462&req=5

f3: Immunohistochemical analysis of macrophages/microglia and iNOS in lesions of N. caninum-infected mouse brain.(A–C) Serial sections of N. caninum-infected mouse brain. (A and A′) HE staining. (A′) A high-magnification image showing focal necrosis with mononuclear cell infiltration and cuffing. (B and B′) Immunohistochemical analysis with anti-Iba1 antibody. Infiltration of activated macrophages/microglia was observed around the necrotic area. (C and C′) Immunohistochemical analysis with an anti-iNOS antibody. Expression of iNOS was detected in inflammatory cells around the necrotic areas.
Mentions: Tachyzoites were found within some lesions, but no tissue cysts were found in the present study. Therefore, the tropism of tissue cysts was not determined histopathologically. We also investigated the distribution of the parasite in the brain with real-time PCR. The numbers of parasites for each area of the brain are shown in Figure 2F. A sporadically high parasite load was detected in the frontal lobe and periaqueductal gray of the symptomatic mice. However we could not evaluate the difference of parasite number among the areas statistically because of small sample number. No association between the parasite load and the severity of the lesions was found. In an immunohistochemical analysis, the infiltration of macrophages or microglia and the production of inducible nitric oxide synthase (iNOS) were predominantly observed in the necrotic and inflammatory lesions (See Figure 3).

Bottom Line: A GOstat analysis predicted that the upregulated genes were involved in the host immune response.Genes whose expression correlated positively and negatively with parasite numbers were involved in the host immune response, and neuronal morphogenesis and lipid metabolic processes, respectively.These results suggest that changes in the gene expression profile associated with neuronal functions as well as immune responses can contribute to the pathogenesis in N. caninum-infected animals.

View Article: PubMed Central - PubMed

Affiliation: National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido, Japan.

ABSTRACT
Neospora caninum is a protozoan parasite that causes neurological disorders in dogs and cattle. It can cause nonsuppurative meningoencephalitis and a variety of neuronal symptoms are observed, particularly in dogs. However, the pathogenic mechanism, including the relationship between the parasite distribution and the clinical signs, is unclear. In this study, to understand the pathogenic mechanism of neosporosis, parasite distribution and lesions were assessed in the brain of mice infected with N. caninum (strain Nc-1). Host gene expression was also analyzed with RNA sequencing (RNA-Seq). The histopathological lesions in the frontal lobe and the medulla oblongata were significantly more severe in symptomatic mice than in asymptomatic mice, although no association between the severity of the lesions and parasite numbers was found. In infected mice, the expression of 772 mouse brain genes was upregulated. A GOstat analysis predicted that the upregulated genes were involved in the host immune response. Genes whose expression correlated positively and negatively with parasite numbers were involved in the host immune response, and neuronal morphogenesis and lipid metabolic processes, respectively. These results suggest that changes in the gene expression profile associated with neuronal functions as well as immune responses can contribute to the pathogenesis in N. caninum-infected animals.

Show MeSH
Related in: MedlinePlus