Neuroprotector effect of melatonin and N-acetilserotonin in the epileptogenesis and in the control of seizures in animals submitted to the pilocarpine model

PURPOSE: The aim of this research was to study the effects of treatment with melatonin and N-acetilserotonin in the development of pilocarpina model of epilepsy in adult male rats. METHODS: Part I - The animals were divided in 4 groups: SALINE - animals that received only saline; SE - animals submitted to status epilepticus (SE); NAS + SE - animals that received pre-treatment with N-acetylserotonin and were submitted to SE and MEL + SE - animals that received pre-treatment with melatonin and were submitted to SE. Part II - The animals were divided in 6 groups: SALINE - animals that received only saline; SE - animals submitted to status epilepticus (SE); PX + SE - animals submitted to pinealectomy and to SE 7 days later; SH + SE - animals submitted to sham-surgery and to SE 7 days later; SE + NAS - animals submitted to SE and treated with N-acetylserotonin (2,5 mg/kg), 30 min, 1 h, 2 h, 4 h, 6 h, 12 h, 24 h, 36 h and 48 h after the SE and SE + MEL - animals submitted to SE and treated with melatonin (2,5 mg/kg), 30 min, 1 h, 2 h, 4 h, 6 h, 12 h, 24 h, 36 h and 48 h after the SE. Following the treatment the animals were continuously video-recorded for 60 days. The behavioral parameters were observed: latency for the SE in minutes, latency for the first spontaneous seizures (ie, duration of the silent period), number of spontaneous seizures during the chronic period and mortality. Five animals per group were perfused for neo-Timm assay. RESULTS: Part I - The animals treated with melatonin and N-acetylserotonin presented an increased of latency for the status epilepticus and decreased number of spontaneous seizures during the chronic period when compared to SE group. The mortality was reduced 100% in animals treated with melatonin and theses animals presented a minor mossy fibers sprouting. Part II - The latency for the first spontaneous seizures and mortality were similar in all groups. The animals treated with melatonin presented a decreased number of spontaneous seizures during the chronic period when compared to PX + SE group and a minor mossy fibers sprouting when compared to SE, SH + SE and PX + SE groups. CONCLUSION: Our data show that the melatonin and N-acetylserotonin have an important neuroprotector effect in the epileptogenesis and in the control of seizures during the chronic period of the pilocarpina model of epilepsy induced by pilocarpina.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaUNIFESP, EPMSciEL

Utilização de peptídeos combinados com nanotecnologia e imagem molecular – novos métodos para diagnóstico e tratamento de doenças neuropsiquiátricas

Inst Israelita Ensino & Pesquisa Albert Einstein, Sao Paulo, BrazilUniv Fed Sao Paulo, LiNC, Sao Paulo, BrazilUniv Fed Sao Paulo, LiNC, Sao Paulo, BrazilWeb of Scienc

Maternal Exercise during Pregnancy Increases BDNF Levels and Cell Numbers in the Hippocampal Formation but Not in the Cerebral Cortex of Adult Rat Offspring

International audienceClinical evidence has shown that physical exercise during pregnancy may alter brain devel- opment and improve cognitive function of offspring. However, the mechanisms through which maternal exercise might promote such effects are not well understood. The present study examined levels of brain-derived neurotrophic factor (BDNF) and absolute cell num- bers in the hippocampal formation and cerebral cortex of rat pups born from mothers exer- cised during pregnancy. Additionally, we evaluated the cognitive abilities of adult offspring in different behavioral paradigms (exploratory activity and habituation in open field tests, spatial memory in a water maze test, and aversive memory in a step-down inhibitory avoid- ance task). Results showed that maternal exercise during pregnancy increased BDNF lev- els and absolute numbers of neuronal and non-neuronal cells in the hippocampal formation of offspring. No differences in BDNF levels or cell numbers were detected in the cerebral cortex. It was also observed that offspring from exercised mothers exhibited better cognitive performance in nonassociative (habituation) and associative (spatial learning) mnemonic tasks than did offspring from sedentary mothers. Our findings indicate that maternal exer- cise during pregnancy enhances offspring cognitive function (habituation behavior and spa- tial learning) and increases BDNF levels and cell numbers in the hippocampal formation of offspring

Reduced IgG anti-small nuclear ribonucleoprotein autoantibody production in systemic lupus erythematosus patients with positive IgM anti-cytomegalovirus antibodies

INTRODUCTION: Systemic lupus erythematosus is characterized by production of autoantibodies to RNA or DNA-protein complexes such as small nuclear ribonucleoproteins (snRNPs). A role of Epstein-Barr virus in the pathogenesis has been suggested. Similar to Epstein-Barr virus, cytomegalovirus (CMV) infects the majority of individuals at a young age and establishes latency with a potential for reactivation. Homology of CMV glycoprotein B (UL55) with the U1snRNP-70 kDa protein (U1-70 k) has been described; however, the role of CMV infection in production of anti-snRNPs is controversial. We investigated the association of CMV serology and autoantibodies in systemic lupus erythematosus. METHODS: Sixty-one Mexican patients with systemic lupus erythematosus were tested for CMV and Epstein-Barr virus serology (viral capsid antigen, IgG, IgM) and autoantibodies by immunoprecipitation and ELISA (IgG and IgM class, U1RNP/Sm, U1-70 k, P peptide, rheumatoid factor, dsDNA, beta2-glycoprotein I). RESULTS: IgG anti-CMV and IgM anti-CMV were positive in 95% (58/61) and 33% (20/61), respectively, and two cases were negative for both. Clinical manifestation and autoantibodies in the IgM anti-CMV+ group (n = 20) versus the IgM anti-CMV(-)IgG+ (n = 39) group were compared. Most (19/20) of the IgM anti-CMV+ cases were IgG anti-CMV+, consistent with reactivation or reinfection. IgM anti-CMV was unrelated to rheumatoid factor or IgM class autoantibodies and none was positive for IgM anti-Epstein-Barr virus-viral capsid antigen, indicating that this is not simply due to false positive results caused by rheumatoid factor or nonspecific binding by certain IgM. The IgM anti-CMV+ group has significantly lower levels of IgG anti-U1RNP/Sm and IgG anti-U1-70 k (P = 0.0004 and P = 0.0046, respectively). This finding was also confirmed by immunoprecipitation. Among the IgM anti-CMV(-) subset, anti-Su was associated with anti-U1RNP and anti-Ro (P < 0.05). High levels of IgG anti-CMV were associated with production of lupus-related autoantibodies to RNA or DNA-protein complex (P = 0.0077). CONCLUSIONS : Our findings suggest a potential role of CMV in regulation of autoantibodies to snRNPs and may provide a unique insight to understand the pathogenesis

Mesenchymal stem cell-like properties of CD133+ glioblastoma initiating cells

Glioblastoma is composed of dividing tumor cells, stromal cells and tumor initiating CD133+ cells. Recent reports have discussed the origin of the glioblastoma CD133+ cells and their function in the tumor microenvironment. The present work sought to investigate the multipotent and mesenchymal properties of primary highly purified human CD133+ glioblastoma-initiating cells. To accomplish this aim, we used the following approaches: i) generation of tumor subspheres of CD133+ selected cells from primary cell cultures of glioblastoma; ii) analysis of the expression of pluripotency stem cell markers and mesenchymal stem cell (MSC) markers in the CD133+ glioblastoma-initiating cells; iii) side-by-side ultrastructural characterization of the CD133+ glioblastoma cells, MSC and CD133+ hematopoietic stem cells isolated from human umbilical cord blood (UCB); iv) assessment of adipogenic differentiation of CD133+ glioblastoma cells to test their MSC-like in vitro differentiation ability; and v) use of an orthotopic glioblastoma xenograft model in the absence of immune suppression. We found that the CD133+ glioblastoma cells expressed both the pluripotency stem cell markers (Nanog, Mush-1 and SSEA-3) and MSC markers. In addition, the CD133+ cells were able to differentiate into adipocyte-like cells. Transmission electron microscopy (TEM) demonstrated that the CD133+ glioblastoma-initiating cells had ultrastructural features similar to those of undifferentiated MSCs. In addition, when administered in vivo to non-immunocompromised animals, the CD133+ cells were also able to mimic the phenotype of the original patient’s tumor. In summary, we showed that the CD133+ glioblastoma cells express molecular signatures of MSCs, neural stem cells and pluripotent stem cells, thus possibly enabling differentiation into both neural and mesodermal cell types