Clarified Açaí ( Euterpe oleracea

Seizures affect about 50 million people around the world. Approximately 30% of seizures are refractory to the current pharmacological arsenal, so, the pursuit of new therapeutic alternatives is essential. Clarified Euterpe oleracea (EO) juice showed anticonvulsant properties similar to diazepam in an in vivo model with pentylenetetrazol, a GABAA receptor blocker. This study investigated the effects of EO on the main GABAergic targets for anticonvulsant drugs, analyzing the effect on the GABA receptor’s benzodiazepine and picrotoxinin binding sites and the GABA uptake. Primary cultures of cortical neurons and astrocytes were treated with EO (0–25%) for up to 90 min. [3H]Flunitrazepam and [3H]TBOB binding, [3H]GABA uptake, cell viability, and morphology were assayed. Nonlethal concentrations of EO increased agonist binding and decreased antagonist binding in cortical neurons. Low concentrations significantly inhibited GABA uptake, especially in astrocytes, suggesting an accumulation of endogenous GABA in the synaptic cleft. The results demonstrate, for the first time, that EO can improve GABAergic neurotransmission via interactions with GABAA receptor and modulation of GABA uptake. Understanding these molecular mechanisms will help in the treatment of seizures and epilepsy, especially in developing countries where geographic isolation and low purchasing power are the main barriers to access to adequate treatment

Adult Hippocampal Neurogenesis in Different Taxonomic Groups: Possible Functional Similarities and Striking Controversies

Adult neurogenesis occurs in many species, from fish to mammals, with an apparent reduction in the number of both neurogenic zones and new neurons inserted into established circuits with increasing brain complexity. Although the absolute number of new neurons is high in some species, the ratio of these cells to those already existing in the circuit is low. Continuous replacement/addition plays a role in spatial navigation (migration) and other cognitive processes in birds and rodents, but none of the literature relates adult neurogenesis to spatial navigation and memory in primates and humans. Some models developed by computational neuroscience attribute a high weight to hippocampal adult neurogenesis in learning and memory processes, with greater relevance to pattern separation. In contrast to theories involving neurogenesis in cognitive processes, absence/rarity of neurogenesis in the hippocampus of primates and adult humans was recently suggested and is under intense debate. Although the learning process is supported by plasticity, the retention of memories requires a certain degree of consolidated circuitry structures, otherwise the consolidation process would be hampered. Here, we compare and discuss hippocampal adult neurogenesis in different species and the inherent paradoxical aspects

Revisiting Astrocytic Roles in Methylmercury Intoxication

Intoxication by heavy metals such as methylmercury (MeHg) is recognized as a global health problem, with strong implications in central nervous system pathologies. Most of these neuropathological conditions involve vascular, neurotransmitter recycling, and oxidative balance disruption leading to accelerated decline in fine balance, and learning, memory, and visual processes as main outcomes. Besides neurons, astrocytes are involved in virtually all the brain processes and perform important roles in neurological response following injuries. Due to astrocytes’ strategic functions in brain homeostasis, these cells became the subject of several studies on MeHg intoxication. The most heterogenous glial cells, astrocytes, are composed of plenty of receptors and transporters to dialogue with neurons and other cells and to monitor extracellular environment responding tightly through fluctuation of cytosolic ions. The overall toxicity of MeHg might be determined on the basis of the balance between MeHg-mediated injury to neurons and protective responses from astrocytes. Although the role of neurons in MeHg intoxication is relatively well-established, the role of the astrocytes is only beginning to be understood. In this review, we update the information on astroglial modulation of the MeHg-induced neurotoxicity, providing remarks on their protective and deleterious roles and insights for future studies.This research was funded by Conselho Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, grant numbers 27724/2018–2 and 307564/2017–7), Ministerio de Ciencia e Innovación (MCINN, grant number PID2019-106285RB-C22) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, grant numbers 88887.200500/2018–00)

In the Heart of the Amazon: Noncommunicable Diseases and Apolipoprotein E4 Genotype in the Riverine Population

The Amazon River basin is the largest tropical forest in the world. Most of the Amazon belongs to Brazil, a developing country that currently faces huge challenges related to the consolidation of its universal healthcare system. Noncommunicable diseases (NCDs) are the leading cause of death in Brazil, accounting for 74% of all deaths, and NCDs are probably underestimated in Amazonian population because of their geographical isolation and the precariousness of riverine communities. Important risk factors, such as genetic susceptibility, remain undetermined in the riverine population. This study performed fasting blood sugar (FBS) and blood pressure measurements and investigated the presence of the ε4 allele of apolipoprotein E (APOE4) to determine the prevalence of diabetes, hypertension and the genetic risk of NCDs. FBS and APOE4 were measured in blood samples from 763 participants using spectrometry and real-time PCR; 67.5% showed altered measurements, and 57.9% had never been diagnosed or treated. Altered FBS was found in 28.3% of the participants, hypertension in 57.6% and APOE4 in 32.0%. The health profile of the riverine population appears to differ from that of urban population in the Amazon. Additional risk factors for NCDs, such as environmental contamination and nutritional transition, may contribute more than increased genetic susceptibility to the prevalence of altered FBS and hypertension. Our results will help guide the development of preventive strategies and governmental actions for more effective management of NCDs in the Amazon area

Is Low Non-Lethal Concentration of Methylmercury Really Safe? A Report on Genotoxicity with Delayed Cell Proliferation.

Human exposure to relatively low levels of methylmercury is worrying, especially in terms of its genotoxicity. It is currently unknown as to whether exposure to low levels of mercury (below established limits) is safe. Genotoxicity was already shown in lymphocytes, but studies with cells of the CNS (as the main target organ) are scarce. Moreover, disturbances in the cell cycle and cellular proliferation have previously been observed in neuronal cells, but no data are presently available for glial cells. Interestingly, cells of glial origin accumulate higher concentrations of methylmercury than those of neuronal origin. Thus, the aim of this work was to analyze the possible genotoxicity and alterations in the cell cycle and cell proliferation of a glioma cell line (C6) exposed to a low, non-lethal and non-apoptotic methylmercury concentration. Biochemical (mitochondrial activity) and morphological (integrity of the membrane) assessments confirmed the absence of cell death after exposure to 3 μM methylmercury for 24 hours. Even without promoting cell death, this treatment significantly increased genotoxicity markers (DNA fragmentation, micronuclei, nucleoplasmic bridges and nuclear buds). Changes in the cell cycle profile (increased mitotic index and cell populations in the S and G2/M phases) were observed, suggesting arrest of the cycle. This delay in the cycle was followed, 24 hours after methylmercury withdrawal, by a decrease number of viable cells, reduced cellular confluence and increased doubling time of the culture. Our work demonstrates that exposure to a low sublethal concentration of MeHg considered relatively safe according to current limits promotes genotoxicity and disturbances in the proliferation of cells of glial origin with sustained consequences after methylmercury withdrawal. This fact becomes especially important, since this cellular type accumulates more methylmercury than neurons and displays a vital role protecting the CNS, especially in chronic intoxication with this heavy metal

Cell proliferation after exposure to methylmercury (MeHg) 3 μM for 24h.

<p>Cellular viability was evaluated at the beginning (day 0) and the end (day 1) of exposure and after 24h (day 2) and 48h (day 3) of MeHg withdrawal (panel A). Number of viable cells were registered on day 2 (panel B). Micrographs (40X) of culture confluence at days 0, 1 and 2 are shown (panel C). Data are shown as mean ± SEM (n = 3–9). Student’s t-test between control and MeHg groups of the same day was performed. *P < 0.01 <i>vs</i> control group of the same day.</p

Alterations of the cell cycle after intoxication with 3 μM of methylmercury (MeHg) for 24h.

<p>Mitotic index (panel A) and cell cycle profile with illustrative spectrograms (panel B) and proportion of events (panel C). Data are shown as mean ± SEM (n = 3). Student’s t-test between control and MeHg groups was performed. *P < 0.01 <i>vs</i> control.</p

Genotoxicity detected after 24h of exposure to 3 μM of methylmercury (MeHg).

<p>DNA fragmentation was analyzed by comet assay (panel A) and indexes of micronuclei, nucleoplasmic bridges and nuclear buds were analyzed by cytokinesis-block micronucleus assay (panel B). Insets show micrographs (100X). Data are reported as mean ± SEM (n = 6). Student’s t-test between control and MeHg groups was performed. *P < 0.01 <i>vs</i> control.</p

Cell survival after exposure to methylmercury (MeHg) for 24h.

<p>Cellular viability of cells intoxicated with increased concentrations (panel A) and number of viable and non-viable cells in control and cells exposed to 3 μM (panel B). Insets show micrographs (40X and 100X). Data are expressed as mean ± SEM (n = 4–9). One-way ANOVA followed by <i>post-hoc</i> Tukey test (panel A) and Student’s t-test between control and MeHg groups (panel B) were performed. *P < 0.01 <i>vs</i> all groups.</p