PMID- 30995165 OWN - NLM STAT- MEDLINE DCOM- 20191217 LR - 20191217 IS - 1937-2345 (Electronic) IS - 0022-3395 (Linking) VI - 105 IP - 2 DP - 2019 Apr TI - Neuroprotection During Neospora caninum Infection Is Related To the Release of Neurotrophic Factors BDNF and NGF. PG - 313-320 AB - Neospora caninum is a parasite that infects many animal species and has tropism for various tissues, particularly the nervous system, where it generally remains in cysts. Under N. caninum infection, glial cells activate immune responses by a Th2 profile, suggesting an immunologically privileged environment that controls parasite proliferation, with neuronal preservation. In this study, we investigated the role of soluble neurotrophic factors released by glial cells on neuronal integrity during N. caninum infection in vitro. Primary cultures of rat glial cells enriched in astrocytes were infected with N. caninum tachyzoites (1:1) for 24 hr. Neuron-glia co-cultures were cultured for 24 hr with conditioned medium from glial cells infected with N. caninum (CM(Nc)) and from uninfected cultures (control). Cell viability was determined through a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test; astrocyte morphology and reactivity were determined through immunocytochemistry for glial fibrillar acid protein (GFAP) and the integrity of neurons through immunocytochemistry for beta-tubulin III. Expression of inflammatory cytokines and neurotrophic factors was determined through RT-qPCR. The MTT test demonstrated that 1:1 was the best parasite/host cell ratio, considering that it was enough to increase metabolism of glial cells when compared with control cultures and was not cytotoxic after 48 hr infection. N. caninum-infected glial cultures responded with astrogliosis characterized by an increase in GFAP expression and increase in IL-10 (2-fold), BDNF (1.6-fold), and NGF (1.7-fold) gene expression. In the neuron/glia co-cultures, it was observed that treatment with CM(Nc) induced neuritis outgrowth without toxicity. Together, these results show that modulatory mechanisms by neurotrophic factors derived from glial cells, primarily astrocytes during the N. caninum infection, can favor neuroprotection. FAU - Grangeiro, Maria Socorro AU - Grangeiro MS AD - 1 Laboratory of Neurochemistry and Cell Biology, Department of Biochemistry and Biophysics, Institute of Health Sciences, Federal University of Bahia, Av. Reitor Miguel Calmon s/no. Vale do Canela, Salvador-BA, 40110-902, Brazil. FAU - Santos, Cleonice Creusa Dos AU - Santos CCD AD - 1 Laboratory of Neurochemistry and Cell Biology, Department of Biochemistry and Biophysics, Institute of Health Sciences, Federal University of Bahia, Av. Reitor Miguel Calmon s/no. Vale do Canela, Salvador-BA, 40110-902, Brazil. FAU - Borges, Julita Maria Pereira AU - Borges JMP AD - 1 Laboratory of Neurochemistry and Cell Biology, Department of Biochemistry and Biophysics, Institute of Health Sciences, Federal University of Bahia, Av. Reitor Miguel Calmon s/no. Vale do Canela, Salvador-BA, 40110-902, Brazil. AD - 2 Department of Science and Technology, University State Southwest of Bahia (UESB), Campus Jequie, Avenida Jose Moreira Sobrinho 398/399 Jequiezinho, Jequie, BA, 45208-091, Brazil. FAU - Sousa, Cleide Dos Santos AU - Sousa CDS AD - 1 Laboratory of Neurochemistry and Cell Biology, Department of Biochemistry and Biophysics, Institute of Health Sciences, Federal University of Bahia, Av. Reitor Miguel Calmon s/no. Vale do Canela, Salvador-BA, 40110-902, Brazil. FAU - Freitas, Simone AU - Freitas S AD - 1 Laboratory of Neurochemistry and Cell Biology, Department of Biochemistry and Biophysics, Institute of Health Sciences, Federal University of Bahia, Av. Reitor Miguel Calmon s/no. Vale do Canela, Salvador-BA, 40110-902, Brazil. FAU - Argolo, Deivison AU - Argolo D AD - 1 Laboratory of Neurochemistry and Cell Biology, Department of Biochemistry and Biophysics, Institute of Health Sciences, Federal University of Bahia, Av. Reitor Miguel Calmon s/no. Vale do Canela, Salvador-BA, 40110-902, Brazil. FAU - de Jesus, Livia Bacelar AU - de Jesus LB AD - 1 Laboratory of Neurochemistry and Cell Biology, Department of Biochemistry and Biophysics, Institute of Health Sciences, Federal University of Bahia, Av. Reitor Miguel Calmon s/no. Vale do Canela, Salvador-BA, 40110-902, Brazil. FAU - Cunha, Elisabete Freire Santos AU - Cunha EFS AD - 1 Laboratory of Neurochemistry and Cell Biology, Department of Biochemistry and Biophysics, Institute of Health Sciences, Federal University of Bahia, Av. Reitor Miguel Calmon s/no. Vale do Canela, Salvador-BA, 40110-902, Brazil. FAU - de Oliveira, Diego Madureira AU - de Oliveira DM AD - 3 University of Brasilia (UNB) Campus Ceilandia, QNN 14 Area Especial Ceilandia, Brasilia-DF, 72220-140 Brazil. FAU - El-Bacha, Ramon Dos Santos AU - El-Bacha RDS AD - 1 Laboratory of Neurochemistry and Cell Biology, Department of Biochemistry and Biophysics, Institute of Health Sciences, Federal University of Bahia, Av. Reitor Miguel Calmon s/no. Vale do Canela, Salvador-BA, 40110-902, Brazil. AD - 4 National Institute of Translational Neuroscience/CNPq, ICB / UFRJ Av. Carlos Chagas Filho 373, CEP 21941-902, Rio de Janeiro, Brazil. FAU - Costa, Silvia Lima AU - Costa SL AD - 1 Laboratory of Neurochemistry and Cell Biology, Department of Biochemistry and Biophysics, Institute of Health Sciences, Federal University of Bahia, Av. Reitor Miguel Calmon s/no. Vale do Canela, Salvador-BA, 40110-902, Brazil. AD - 4 National Institute of Translational Neuroscience/CNPq, ICB / UFRJ Av. Carlos Chagas Filho 373, CEP 21941-902, Rio de Janeiro, Brazil. FAU - de Fatima Dias Costa, Maria AU - de Fatima Dias Costa M AD - 1 Laboratory of Neurochemistry and Cell Biology, Department of Biochemistry and Biophysics, Institute of Health Sciences, Federal University of Bahia, Av. Reitor Miguel Calmon s/no. Vale do Canela, Salvador-BA, 40110-902, Brazil. AD - 4 National Institute of Translational Neuroscience/CNPq, ICB / UFRJ Av. Carlos Chagas Filho 373, CEP 21941-902, Rio de Janeiro, Brazil. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Parasitol JT - The Journal of parasitology JID - 7803124 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Culture Media, Conditioned) RN - 0 (DNA, Complementary) RN - 0 (Nerve Growth Factors) RN - 0 (Neurotrophin 3) RN - 0 (RNA, Protozoan) RN - 9061-61-4 (Nerve Growth Factor) RN - P658DCA9XD (neurotrophin 4) SB - IM MH - Analysis of Variance MH - Animals MH - Animals, Newborn MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Cells, Cultured MH - Cerebral Cortex/cytology MH - Chlorocebus aethiops MH - Coculture Techniques MH - Culture Media, Conditioned MH - DNA, Complementary/biosynthesis MH - Neospora/genetics/*physiology MH - Nerve Growth Factor/*metabolism MH - Nerve Growth Factors/metabolism MH - Neuroglia/cytology/metabolism/*parasitology MH - Neurons/cytology MH - Neurotrophin 3/metabolism MH - RNA, Protozoan/genetics/isolation & purification MH - Rats MH - Rats, Wistar MH - Real-Time Polymerase Chain Reaction MH - Vero Cells OTO - NOTNLM OT - Neuron-Glial Culture OT - Neuroprotection OT - Neurotrophic Factor EDAT- 2019/04/18 06:00 MHDA- 2019/12/18 06:00 CRDT- 2019/04/18 06:00 PHST- 2019/04/18 06:00 [entrez] PHST- 2019/04/18 06:00 [pubmed] PHST- 2019/12/18 06:00 [medline] AID - 10.1645/18-81 [pii] PST - ppublish SO - J Parasitol. 2019 Apr;105(2):313-320.