Hippocampus and Prefrontal Cortex Modulation of Contextual Fear Memory Is Dissociated by Inhibiting De Novo Transcription During Late Consolidation.

To uncover the factors that dictate the persistence of a memory, it is critical to determine the molecular basis of consolidation. Here, we submitted male adult C57/BL6 mice to contextual fear conditioning using 1US (US: foot-shock, 0.7 mA, 2 s) or 5US, to generate recent (24 to 48 h) and remote (30 days) memories, respectively. To access the functional role of de novo transcription, we injected actinomycin D (ActD: 2.5 ng/side) directly into the dorsal hippocampus (HIP) or dorsomedial prefrontal cortex (dmPFC), 0 (early consolidation) or 12 h (late consolidation) after training. Our results showed that de novo transcription at 0 h was required for recent and remote memories. However, 12 h was a critical time point to memory persistence. In the dHIP, de novo transcription at 12 h post-training differentiated the recent memory from the remote. In the dmPFC, ActD affected memory formation depending on the training intensity (1 or 5US). Specifically, freezing was amplified after 5US conditioning. Furthermore, inhibiting de novo transcription at 12 h post-training in the dmPFC rapidly increased c-Fos expression in the amygdala. Altogether, our results indicate that contextual fear memory duration is particularly sensitive to de novo transcription in the dHIP and dmPFC, at a specific time point of late consolidation.

Estradiol effect on short-term object memory under hypocholinergic condition.

Estrogens positively affect object recognition memory (ORM). However, whether this effect rely on acetylcholine is unknown. Here we investigated if 17ß-estradiol (E2) would be able to recover ORM deficits in animals with decreased expression of the Vesicular Acetylcholine Transporter (VAChT KDHET). We found that E2 improved short-term ORM (STM) in VAChT KDHET male and in OVX female mutant mice. However, E2 did not recover long-term (LTM) ORM in both sexes. Next, we tested whether hippocampal ERs activation could also rescue STM in mutant mice. Our results showed that ERα seems to be both sufficient and necessary for STM consolidation in female VAChT KDHET. Differently, in male, both ERα and ERß activation recovered STM. In addition, we tested whether mRNA level of estrogen receptors (ER) is also sensitive to VAChT expression. Female mutant mice showed lower levels of ER alpha (ERα) mRNA in the hippocampus, while no differences in male were observed. Together, our results showed that under hypocholinergic function, E2 improve short-term object recognition in both male and female. Furthermore, we showed that changes in VAChT expression might potentially modulate hippocampal ERα expression in a sex-dependent-manner.

Exploring the impact of malocclusion and dentofacial anomalies on the occurrence of traumatic dental injuries in adolescents.

OBJECTIVE: To investigate the association between malocclusion/dentofacial anomalies and traumatic dental injuries (TDI) in adolescents. MATERIALS AND METHODS: The sample of this cross-sectional study comprised 509 adolescents aged 11 to 14 years enrolled at public schools in the city of Osório, southern Brazil. Parents answered a structured questionnaire addressing demographic and socioeconomic characteristics. An examiner who had undergone a training and calibration exercise recorded malocclusion/dentofacial anomalies (Dental Aesthetic Index, DAI), TDI (Andreasen), and dental caries (World Health Organisation). Statistical analyses (SPSS software) involved Poisson regression with robust variance. RESULTS: The prevalence of TDI was 11.6%, and the prevalence of defined, severe, and handicapping malocclusion was 24.0%, 21.6%, and 22.0%, respectively. The multivariate analysis demonstrated that the probability of TDI was approximately twofold higher among adolescents with severe malocclusion (prevalence ratio [PR] 2.22; 95% confidence interval [CI] 1.14-4.31) and handicapping malocclusion (PR 1.95; 95% CI 1.01-3.85) in comparison to those with normal occlusion or minor malocclusion. Defined malocclusion was not significantly associated with the outcome. Among the dentofacial anomalies evaluated, the probability of TDI was nearly twofold higher among adolescents with overjet greater than 3 mm (PR 1.96; 95% CI 1.14-3.37) and 2.2-fold higher among those with an abnormal molar relationship (PR 2.24; 95% CI 1.17-4.32), after controlling for confounding variables. CONCLUSIONS: Severe and handicapping malocclusion, accentuated overjet, and abnormal molar relationship were strongly associated with the occurrence of TDI. Future studies should investigate whether the treatment of these conditions can help reduce the occurrence of TDI in adolescents.

Object recognition memory deficit and depressive-like behavior caused by chronic ovariectomy can be transitorialy recovered by the acute activation of hippocampal estrogen receptors.

It is well known that estradiol (E2) replacement therapy is effective on restoring memory deficits and mood disorders that may occur during natural menopause or after surgical ovarian removal (ovariectomy, OVX). However, it is still unknown the effectiveness of acute and localized E2 administration on the effects of chronic OVX. Here we tested the hypothesis that the intra-hippocampal E2 infusion, as well as specific agonists of estrogen receptors (ERs) alpha (ERα) and beta (ERß), are able to mend novel object recognition (NOR) memory deficit and depressive-like behavior caused by 12 weeks of OVX. We found that both ERα and ERß activation, at earlier stages of consolidation, recovered the NOR memory deficit caused by 12 w of OVX. Conversely, only the ERß activation was effective in decreasing the depressive-like behavior caused by 12 w of OVX. Furthermore, we investigated the effect of OVX on hippocampal volume and ERs expression. The structural MRI showed no alteration in the hippocampus volume of 12 w OVX animals. Interestingly, ERα expression in the hippocampus decreased after one week of OVX, but increased in 12 w OVX animals. Overall, we may conclude that the chronic estrogen deprivation, induced by 12 weeks of OVX, modulates the hippocampal ERα expression and induces NOR memory deficit and depressive-like behaviors. Nonetheless, it is noteworthy that the acute effects of E2 on NOR memory and depressive-like behavior are still apparent even after 12 weeks of OVX.

Estradiol enhances object recognition memory in Swiss female mice by activating hippocampal estrogen receptor α.

In rodents, 17ß-estradiol (E2) enhances hippocampal function and improves performance in several memory tasks. Regarding the object recognition paradigm, E2 commonly act as a cognitive enhancer. However, the types of estrogen receptor (ER) involved, as well as the underlying molecular mechanisms are still under investigation. In the present study, we asked whether E2 enhances object recognition memory by activating ERα and/or ERß in the hippocampus of Swiss female mice. First, we showed that immediately post-training intraperitoneal (i.p.) injection of E2 (0.2 mg/kg) allowed object recognition memory to persist 48 h in ovariectomized (OVX) Swiss female mice. This result indicates that Swiss female mice are sensitive to the promnesic effects of E2 and is in accordance with other studies, which used C57/BL6 female mice. To verify if the activation of hippocampal ERα or ERß would be sufficient to improve object memory, we used PPT and DPN, which are selective ERα and ERß agonists, respectively. We found that PPT, but not DPN, improved object memory in Swiss female mice. However, DPN was able to improve memory in C57/BL6 female mice, which is in accordance with other studies. Next, we tested if the E2 effect on improving object memory depends on ER activation in the hippocampus. Thus, we tested if the infusion of intra-hippocampal TPBM and PHTPP, selective antagonists of ERα and ERß, respectively, would block the memory enhancement effect of E2. Our results showed that TPBM, but not PHTPP, blunted the promnesic effect of E2, strongly suggesting that in Swiss female mice, the ERα and not the ERß is the receptor involved in the promnesic effect of E2. It was already demonstrated that E2, as well as PPT and DPN, increase the phospho-ERK2 level in the dorsal hippocampus of C57/BL6 mice. Here we observed that PPT increased phospho-ERK1, while DPN decreased phospho-ERK2 in the dorsal hippocampus of Swiss female mice subjected to the object recognition sample phase. Taken together, our results suggest that the type of receptor as well as the molecular mechanism used by E2 to improve object memory may differ in Swiss female mice.

Sensibilidade da técnica de reação em cadeia da polimerase para HIV-1 em relação à técnica de ensaio imunoenzimático / Polymerase chain reaction sensitivity against enzyme immuno assay test virus HIV -1

O vírus da imunodeficiência humana (HIV) é o agente etiológico da Síndrome da Imunodeficiência Adquirida, AIDS, uma doença de grande preocupaçäo médica. O genoma deste vírus encontra-se arranjado em nove genes individuais e por duas estruturas idênticas denominadas de repetiçöes terminais nas extremidades 5' e 3'. Tivemos como objetivo analisar a sensibilidade do teste da reaçäo em cadeia da polimerase (PCR) e o teste de ensaio imunoenzimático (ELISA), como teste para triagem de doadores de sangue para HIV. Foram analisadas 200 amostras de doadores e pacientes, da Fundaçäo HEMOPA, com padräo positivo e indeterminado no teste ELISA. Na triagem sorológica pelo ELISA tiveram como resultado 35 amostras positivas, 75 amostras negativas e 90 amostras indeterminadas as quais foram submetidas ao teste pela PCR. Vinte e cinco amostras tiveram resultado positivo e 175 amostras negativas. Com estes resultados concluímos que a reaçäo de PCR apresenta-se positiva somente nas amostras em que o teste ELISA apresenta relaçäo DO/cutoff, acima de 3

Chromosome fragility in hematologic disease presumably induced by environmental pollutants

Chromosome instability consists of chromosome abnoprmalities as multiple breaks in in metaphase chromosomes in syndromes of chromosaome instability such as fanconi's anemia (FA) which is mainly characaterized by bone marrow aplasia; some cases progress to acute leukemia. FA is a hereditary disease with recessive and monogenic transmission. This pair of mutated genes is related to chromosome fragility and therefore is responsible for the inefficiency of DNA repair. In normal individuals, these genes are assumed to be expressed normally, but their products ara insufficient to perform DNA repair when the intensity of the polluting agent lelads to exposure above basal levels. In the present study, the bone marrow of four patients with different hematologic diseases was submitted to cytogenetic analysis. Two had aplastic anemia, and one bad lymphoblastic leukemia. These patients were from towns unb the Amazon Region where the mercuri used for gold prospecting and the substances used and/or released in aluminium mining have been introduced into the environment. The last patient had fanconi's anemia and was used as a model in the discussion of the results. The cytogenetic findings were similar for all patients, the major ones being chromosome fragmentation and pulverization. In view of these findings, we believe that chromosome fragility, observed in the first three patients, presumably was induced by environmental pllutants

Cariótipo de paciente com leucemia mielóide crônica tratado com interferon / Karyotype of the chronic myeloid leukemia patient treated with interferon

Neste trabalho, estudamos citogeneticamente um paciente com LMC tratado com interferon. Foram analisadas 12 células metafásicas. O cromossomo Pb foi encontrado em 100 por cento das células analisadas e apenas uma apresentou isocromossomo 17q. Este achado, apesar de näo ser clonal, pode indicar prenúncio da fase blástica. Porém, o tratamento com interferon pode estar exercendo pressäo sobre as células i(17q), näo permitindo que proliferem bloqueando o início da fase blástica. Portanto acreditamos que o tratamento com interferon é capaz de sprimir as células com alteraçöes cromossômicas pós-philadelfia, melhorando o prognóstico do paciente