Apoptosis in the <i>Cerebellum</i> of Dogs with Distemper

Moro, Luciana; Martins, Almir de Sousa; Alves, Camille Marques; Santos, F.G.A.; Puerto, Helen L. Del; Vasconcelos, A.C.

doi:10.1046/j.1439-0450.2003.00657.x

Cited by 27 publications

(28 citation statements)

References 27 publications

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“…CDV infection caused apoptosis of Vero cells (30) and activated peripheral blood mononuclear cells in vitro (45). In vivo apoptosis was seen in the cerebellum and retropharyngeal lymph nodes of both naturally and experimentally CDV infected dogs (28,29). In vitro CDVeGFP infection of the canine cell lines CLGL-90 and 17-71 led to substantial cell death via apoptosis, as evidenced by the typical ''DNA laddering'' of genomic DNA and the increased binding of Annexin V (Fig.…”

Section: Discussionmentioning

confidence: 96%

In vitroCanine Distemper Virus Infection of Canine Lymphoid Cells: A Prelude to Oncolytic Therapy for Lymphoma

Suter¹,

Chein²,

Messling

et al. 2005

Clinical Cancer Research

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Purpose: Measles virus (MV) causes the regression of human lymphoma xenografts. The purpose of this study was to determine if canine lymphoid cells could be infected in vitro with MV or canine distemper virus (CDV, the canine Morbillivirus equivalent of MV) and determine if in vitro viral infection leads to apoptotic cell death. Experimental Design: Reverse transcriptase-PCR was used to examine the expression of both signal lymphocyte activation molecule (CD150) and membrane cofactor molecule (CD46) mRNA. An attenuated CDV expressing enhanced green fluorescent protein was used to infect canine cells in vitro. Both flow cytometry and reverse transcriptase-PCR was used to document CDV infection. Cell death was examined using a propidium iodide staining assay and Annexin V binding. Results: Canine lymphoid cell lines and neoplastic B and T lymphocytes collected from dogs with spontaneous lymphoma expressed the Morbillivirus receptor CD150 mRNA. In contrast, only neoplastic lymphocytes expressed detectable levels of CD46 mRNA. Although MV did not infect canine cells, CDV efficiently infected between 40% and 70% of all three canine lymphoid lines tested. More importantly, CDV infected 50% to 90% of neoplastic lymphocytes isolated from dogs with both B and T cell lymphoma. Apoptosis of CDV-infected cell lines was documented. Conclusions: Attenuated CDV may be a useful treatment for canine lymphoma. As such, dogs with lymphoma may represent a biologically relevant large animal model to investigate the feasibility, safety, and efficacy of Morbillivirus therapy in a clinical setting with findings that may have direct applicability in the treatment of human non-Hodgkin's lymphoma.

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Section: Discussionmentioning

confidence: 96%

In vitroCanine Distemper Virus Infection of Canine Lymphoid Cells: A Prelude to Oncolytic Therapy for Lymphoma

Suter¹,

Chein²,

Messling

et al. 2005

Clinical Cancer Research

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“…Moro et al (2003b) and Kumagai et al (2004) observed that CD causes apoptosis in the lymph nodes. Moro et al (2003a) also observed apoptosis in the cerebellum, and Schobesberger et al (2005) observed that CDV infection induced apoptosis of lymphocytes and monocytes. Apoptosis can be triggered by various physiological and pathological stimuli, and it is prevalent in several immunosuppressive diseases of humans and animals (Ameisen and Capron, 1991;Lam and Vasconcelos, 1994).…”

Section: Introductionmentioning

confidence: 93%

“…In CDV-infected dogs apoptosis was reported to occur in vitro and in vivo (Guo and Lu, 2000;Moro et al, 2003a). Moro et al (2003b) and Kumagai et al (2004) observed that CD causes apoptosis in the lymph nodes.…”

Section: Introductionmentioning

confidence: 99%

Caspase-3/-8/-9, Bax and Bcl-2 expression in the cerebellum, lymph nodes and leukocytes of dogs naturally infected with canine distemper virus

Puerto¹,

Martins²,

Moro³

et al. 2010

Genet. Mol. Res.

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ABSTRACT. Canine distemper is an immunosuppressive disease caused by the canine distemper virus (CDV). Pathogenesis mainly involves the central nervous system and immunosuppression. Dogs naturally infected with CDV develop apoptotic cells in lymphoid tissues and the cerebellum, but this apoptotic mechanism is not well characterized. To better understand this process, we evaluated the expression of Bax, Bcl-2, and caspase-3, -8 and -9, by evaluating mRNA levels in the peripheral blood, lymph nodes and cerebellum of CDV-infected (CDV+) and uninfected (CDV-) dogs by real-time polymerase chain reaction (PCR). Blood samples from 12 CDV+ and 8 CDV-dogs, diagnosed by reverse transcription-PCR, were subjected to hematological analysis and apoptotic gene expression was evaluated using real-time-PCR. Tissues from the cerebellum and lymph nodes of four CDV+ and three CDVdogs were also subjected to real time-PCR. No significant differences were found between CDV+ and CDV-dogs in the hemotological results or in the expression of caspase-3, -8, -9, Bax, and Bcl-2 in the peripheral blood. However, expression of Bax, caspase-3, -8 and -9 was significantly higher in the cerebellum of CDV+ compared to CDV-dogs. Expression of caspase-3 and -8 was significantly higher in the lymph nodes of CDV+ compared to CDV-dogs. We concluded that infection with CDV induces apoptosis in the cerebellum and lymph nodes in different ways. Lymph node apoptosis apparently occurs via caspase-3 activation, through the caspase-8 pathway, and cerebellum apoptosis apparently occurs via caspase-3 activation, through the caspase-8 and mitochondrial pathways.

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“…It is suggested that granular cells might enter apoptosis through direct lesion by CDV and secondary lesion as a result of previous glial cells impairment. Some searchers (13,14) reported apoptosis in astrocytic syncytia in vitro unlike these studies. Moro et all (14) reported TUNEL reaction in inclusion bodies, several gemistocytes, Gitter cells in white matter and the granular layer of grey matter.…”

Section: Discussionmentioning

confidence: 85%

“…In the case of CDV, cell death is observed during the infection (15). Some searchers reported that CD causes apoptosis in the brain and lymph nodes (7,12,13).…”

Section: Introductionmentioning

confidence: 99%

Distemper virus-induced apoptotic changes in cerebellum

Vural¹,

Alçığır²

2010

Ankara Üniversitesi Veteriner Fakültesi Dergisi

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Summary:In the study, it was purposed that detection of apoptotic changes with terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-digoxigenin nick end-labelling (TUNEL) method in the cerebellum of 10 dogs (n:3 females, n:7 males), varied 3 months to 2.5 years-old, different breed (1 Husky, 9 Mongrel) and sex (3 females, 7 males) in distemper disease. Histopathologically, acute (n:4) and chronic (n:6) nonpurulent encephalitis, moderate and/or mild demyelination, and intranuclear inclusion bodies were seen. Immunohistochemically distemper virus antigen was also detected in demyelinated white matter, astrocytes, and inclusion bodies in all dogs by using monoclonal canine distemper virus nucleoprotein sera. Morphologically multiple consendations of nuclear chromatin in astrocytes were found with Cresyl violet stain. TUNEL reaction in markedly astrocytes localized surrounding the demyelination areas, rarely inclusion bodies, gemistocytic astrocytes, Gitter cells in white matter and granular layer of cerebellum was demonstrated. The reactions in chronic inflammatory lesions were also detected in perivascular mononuclear cells.Key words: Dog, distemper virus, apoptosis, TUNEL Distemper virusuna bağlı serebellumda oluşan apoptotik değişikliklerÖzet: Bu çalışmada, canine distemper virusu belirlenen 3 ay-2.5 yaşlı, değişik ırk (1 Husky, 9 melez) ve cinsiyetteki (3 dişi, 7 erkek) 10 adet köpeğin serebellumunda TUNEL (terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-digoxigenin nick endlabeling) metodu ile gözlenen apoptotik değişiklikler araştırıldı. Histopatolojik incelemede 4 hayvanda akut, 6 hayvanda da kronik nonpurulent ensefalitise ve demyelinasyona (hafif ve/veya orta şiddette) ilgili bulgular gözlendi. Monoclonal canine distemper virus nucleoprotein serumu kullanılarak yapılan immunohistokimyasal boyamada demyelinize beyaz maddede, astrositlerde ve inkluzyon cisimciklerinde distemper virusu antijeni saptandı. Morfolojik olarak Cresyl violet boyamasında, astrositlerde kromatinin kaba partiküller halinde çekirdek membranına yakın olarak toplandığı görüldü. TUNEL metodu ile yapılan boyamalarda ise akut olgularda daha yoğun olmak üzere özellikle demyelinize alanların etrafında bulunan astrositlerde, daha nadir olarak da inkluzyon cisimciklerinde, gemistositik astrositlerde, Gitter hücrelerinde, granuler tabaka hücrelerinde ve perivasküler mononüklear hücrelerde apoptotik değişiklikler saptandı.

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Apoptosis in the Cerebellum of Dogs with Distemper

Cited by 27 publications

References 27 publications

In vitroCanine Distemper Virus Infection of Canine Lymphoid Cells: A Prelude to Oncolytic Therapy for Lymphoma

In vitroCanine Distemper Virus Infection of Canine Lymphoid Cells: A Prelude to Oncolytic Therapy for Lymphoma

Caspase-3/-8/-9, Bax and Bcl-2 expression in the cerebellum, lymph nodes and leukocytes of dogs naturally infected with canine distemper virus

Distemper virus-induced apoptotic changes in cerebellum

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