UNIVERSIDADE FEDERAL DO RIO GRANDE DO NORTE iNSTITUTO DO CÉREBRO
Boletim de Publicações
outubro a dezembro
Natal2018
APRESENTAÇÃO
Este boletim é uma fonte de informação secundária destinada a promover o acesso e a
divulgação da produção científica dos pesquisadores do Instituto do Cérebro (ICe) da
Universidade Federal do Rio Grande do Norte (UFRN). Esta edição reuniu artigos publicados
entre os meses de outubro a dezembro de 2018. Além de apresentar o título e o resumo dos
documentos, fornece um link de acesso ao texto completo, preferencialmente pelo Repositório
Institucional desta Universidade.
O ICe é Unidade Acadêmica Especializada que passou a integrar a estrutura
acadêmica e administrativa da UFRN em 29 de dezembro de 2010, por meio da resolução no
016/2010 do Conselho Universitário (CONSUNI). Essa Unidade é voltada para o
desenvolvimento da tríade ensino, pesquisa e extensão, com forte ação para a
internacionalização dos programas na área de Neurociências, abrangendo os Cursos de:
Pós-Graduação Stricto Sensu em Neurociências, em nível de Mestrado e Doutorado.
Bacharelado em Ciências e Tecnologia, com formação generalista no eixo de
Neurociências.
SUMÁRIO
ARTIGO
S
Non-visual exploration of novel objects increases the levels of plasticity factors in the rat primary visual cortex..................................................................................................................5
Characterizing speed cells in the rat hippocampus.....................................................................6
Acute effects of ayahuasca in a juvenile non-human primate model of depression...................7
Evidence of müller glia conversion into retina ganglion cells using neurogenin2.....................9
Social interactions and androgens levels in marmosets (Callithrix jacchus) in field and laboratory studies: a preliminary investigation of the Challenge Hypothesis..........................10
Sex-biased gene expression in the frontal cortex of common marmosets (Callithrix jacchus) and potential behavioral correlates...........................................................................................11
Consistency of three different questionnaires for evaluating sexual function in healthy young women.......................................................................................................................................13
Brain derived neutrophic factor, a link of aerobic metabolism to neuroplasticity....................15
Uncovering association networks through an eQTL analysis involving human miRNAs and lincRNAs...................................................................................................................................16
Resveratrol decreases the expression of genes involved in inflammation through transcriptional regulation..........................................................................................................17
Computational models of memory consolidation and long-term synaptic plasticity during sleep..........................................................................................................................................19
The maturation of speech structure in psychosis is resistant to formal education....................20
Decifrar o enigma da política de drogas requer mais ciência do que nunca.............................21
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ARTIGOS
5
Pereira CM, Freire MAM, Santos JR, Guimarães JS, Dias-Florencio G, Santos S, et al. Non-visual exploration of novel objects increases the levels of plasticity factors in the rat primary visual cortex. PeerJ., 2018; 6:e5678. doi:10.7717/peerj.5678
Non-visual exploration of novel objects increases the levels of plasticity factors in the rat
primary visual cortex
Abstract
BACKGROUND: Historically, the primary sensory areas of the cerebral cortex have been
exclusively associated with the processing of a single sensory modality. Yet the presence of
tactile responses in the primary visual (V1) cortex has challenged this view, leading to the
notion that primary sensory areas engage in cross-modal processing, and that the associated
circuitry is modifiable by such activity. To explore this notion, here we assessed whether the
exploration of novel objects in the dark induces the activation of plasticity markers in the V1
cortex of rats.
METHODS: Adult rats were allowed to freely explore for 20 min a completely dark box with
four novel objects of different shapes and textures. Animals were euthanized either 1 (n = 5)
or 3 h (n = 5) after exploration. A control group (n = 5) was placed for 20 min in the same
environment, but without the objects. Frontal sections of the brains were submitted to
immunohistochemistry to measure protein levels of egr-1 and c-fos, and phosphorylated
calcium-dependent kinase (pCaKMII) in V1 cortex.
RESULTS: The amount of neurons labeled with monoclonal antibodies against c-fos, egr-1 or
pCaKMII increased significantly in V1 cortex after one hour of exploration in the dark. Three
hours after exploration, the number of labeled neurons decreased to basal levels.
CONCLUSIONS: Our results suggest that non-visual exploration induces the activation of
immediate-early genes in V1 cortex, which is suggestive of cross-modal processing in this
area. Besides, the increase in the number of neurons labeled with pCaKMII may signal a
condition promoting synaptic plasticity.
Keywords: Immediate-early gene. CaMKII. Phosphorylation. Cross-modal processing.
Visual cortex.
URI: https://repositorio.ufrn.br/jspui/handle/123456789/25929
6
Góis ZHT, Tort ABL. Characterizing speed cells in the rat hippocampus. Cell Rep., 2018;25(7):1872-84.e4. doi: 10.1016/j.celrep.2018.10.054
Characterizing speed cells in the rat hippocampus
Abstract
Spatial navigation relies on visual landmarks as well as on self-motion information. In
familiar environments, both place and grid cells maintain their firing fields in darkness,
suggesting that they continuously receive information about locomotion speed required for
path integration. Consistently, "speed cells" have been previously identified in the
hippocampal formation and characterized in detail in the medial entorhinal cortex. Here we
investigated speed-correlated firing in the hippocampus. We show that CA1 has speed cells
that are stable across contexts, position in space, and time. Moreover, their speed-correlated
firing occurs within theta cycles, independently of theta frequency. Interestingly, a
physiological classification of cell types reveals that all CA1 speed cells are inhibitory. In
fact, while speed modulates pyramidal cell activity, only the firing rate of interneurons can
accurately predict locomotion speed on a sub-second timescale. These findings shed light on
network models of navigation.
Keywords: CA1. Hippocampus. Neuronal coding. Path integration. Place cells. Rate coding.
Spatial navigation. Speed cells. Theta.
URI: https://repositorio.ufrn.br/jspui/handle/123456789/26422
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Silva FS, Silva EAS, Sousa Jr. GM, Maia-de-Oliveira JP, Soares-Rachetti VP, Araujo DB, et al. Acute effects of ayahuasca in a juvenile non-human primate model of depression. Brazilian Journal of Psychiatry, 2018. doi: 10.1590/1516-4446-2018-0140
Acute effects of ayahuasca in a juvenile non-human primate model of depression
Abstract
OBJECTIVE: The incidence rate of major depression in adolescents reaches approximately
14%. This disorder is usually recurrent, without remission of symptoms even after
pharmacological treatment, and persists throughout adult life. Since the effects of
antidepressants take approximately 2 weeks to begin, new pharmacological therapies are
under continuous exploration. Recent evidence suggests that psychedelics could produce rapid
antidepressant effects. In this study, we evaluated the potential antidepressant effects of
ayahuasca in a juvenile non-human primate model of depression.
METHODS: While living with their families, juvenile marmosets (8 males; 7 females) were
observed on alternate days for four weeks during a baseline phase. This was followed by 8
weeks of an induced depressive state protocol, the social isolated context (IC), in which the
animals were monitored in the first and last weeks. Subsequently, five males and four females
were randomly selected for treatment, first with a single administration of saline vehicle (1.67
mL/300 g of body weight, via gavage), followed by a single dose of ayahuasca (1.67 mL/300
g of body weight, via gavage). Both phases lasted 1 week and the animals were monitored
daily. A third week of sampling was called the tardive-pharmacological effects phase. In all
phases the marmosets were assessed for behavior, fecal cortisol levels, and body weight.
RESULTS: After IC, the animals presented typical hypocortisolemia, but cortisol recovered to
baseline levels 24 h after an acute dose of ayahuasca; this recovery was not observed in
vehicle-treated animals. Additionally, in males, ayahuasca, but not the vehicle, reduced
scratching, a stereotypic behavior, and increased feeding. Ayahuasca treatment also improved
body weight to baseline levels in both sexes. The ayahuasca-induced behavioral response had
long-term effects (14 days). Thus, in this translational juvenile animal model of depression,
ayahuasca presented beneficial effects.
CONCLUSIONS: These results can contribute to the validation of ayahuasca as an
antidepressant drug and encourage new studies on psychedelic drugs as a tool for treating
mood disorders, including for adolescents with early-onset depression.
Keywords: Translational animal model. Non-human primate. Common marmoset. Marmoset.
Cortisol. Early-age depression. Psychedelic drugs.
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URI: https://repositorio.ufrn.br/jspui/handle/123456789/26423
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Guimarães RPM, Landeira BS, Coelho DM, Golbert DCF, Silveira MS, Costa MR, et al. Evidence of müller glia conversion into retina ganglion cells using neurogenin2. Frontiers in Cellular Neuroscience, 2018;12(410). doi: 10.3389/fncel.2018.00410
Evidence of müller glia conversion into retina ganglion cells using neurogenin2
Abstract
Degenerative retinopathies are the leading causes of irreversible visual impairment in the
elderly, affecting hundreds of millions of patients. Müller glia cells (MGC), the main type of
glia found in the vertebrate retina, can resume proliferation in the rodent adult injured retina
but contribute weakly to tissue repair when compared to zebrafish retina. However, postnatal
and adult mouse MGC can be genetically reprogrammed through the expression of the
transcription factor (TF) Achaete-scute homolog 1 (ASCL1) into induced neurons (iNs),
displaying key hallmarks of photoreceptors, bipolar and amacrine cells, which may contribute
to regenerate the damaged retina. Here, we show that the TF neurogenin 2 (NEUROG2) is
also sufficient to lineage-reprogram postnatal mouse MGC into iNs. The efficiency of MGC
lineage conversion by NEUROG2 is similar to that observed after expression of ASCL1 and
both TFs induce the generation of functionally active iNs. Treatment of MGC cultures with
EGF and FGF2 prior to Neurog2 or Ascl1 expression enhances reprogramming efficiencies,
what can be at least partially explained by an increase in the frequency of MGCs expressing
sex determining region Y (SRY)-box 2 (SOX2). Transduction of either Neurog2 or Ascl1 led
to the upregulation of key retina neuronal genes in MGC-derived iNs, but only NEUROG2
induced a consistent increase in the expression of putative retinal ganglion cell (RGC) genes.
Moreover, in vivo electroporation of Neurog2 in late progenitors from the neonatal rat retina,
which are transcriptionally similar to MGCs, also induced a shift in the generation of retinal
cell subtypes, favoring neuronal differentiation at the expense of MGCs and resuming the
generation of RGCs. Altogether, our data indicate that NEUROG2 induces lineage conversion
of postnatal rodent MGCs into RGC-like iNs in vitro and resumes the generation of this
neuronal type from late progenitors of the retina in vivo.
Keywords: Retina. Müller glia cells. Induced neurons. Lineage-reprogramming.
Neurogenin2. Ascl1. Retina ganglion cells.
URI: https://repositorio.ufrn.br/jspui/handle/123456789/26100
10
Sousa MBC, Pontes MC, Galvão ACM, Silva HPAD, Galvão-Coelho NL. Social interactions and androgens levels in marmosets (Callithrix jacchus) in field and laboratory studies: a preliminary investigation of the Challenge Hypothesis. Gen Comp Endocrinol., 2018. doi: 10.1016/j.ygcen.2018.07.016
Social interactions and androgens levels in marmosets (Callithrix jacchus) in field and
laboratory studies: a preliminary investigation of the Challenge Hypothesis
URI: https://repositorio.ufrn.br/jspui/handle/123456789/26424
11
Nogueira VB, Imparato DO, Souza SJ, Sousa MBC. Sex-biased gene expression in the frontal cortex of common marmosets (Callithrix jacchus) and potential behavioral correlates. Brain Behav., 2018;8(12):e01148. doi: 10.1002/brb3.1148
Sex-biased gene expression in the frontal cortex of common marmosets (Callithrix
jacchus) and potential behavioral correlates
Abstract
INTRODUCTION: The common marmoset (Callithrix jacchus), a small New World monkey,
has been widely used as a biological model in neuroscience to elucidate neural circuits
involved in cognition and to understand brain dysfunction in neuropsychiatric disorders. In
this regard, the availability of gene expression data derived from next-generation sequencing
(NGS) technologies represents an opportunity for a molecular contextualization. Sexual
dimorphism account for differences in diseases prevalence and prognosis. Here, we explore
sex differences on frontal cortex of gene expression in common marmoset's adults.
METHODS: Gene expression profiles in six different tissues (cerebellum, frontal cortex,
liver, heart, and kidney) were analyzed in male and female marmosets. To emphasize the
translational value of this species for behavioral studies, we focused on sex-biased gene
expression from the frontal cortex of male and female in common marmosets and compared
to humans (Homo sapiens).
RESULTS: In this study, we found that frontal cortex genes whose expression is male-biased
are conserved between marmosets and humans and enriched with "house-keeping" functions.
On the other hand, female-biased genes are more related to neural plasticity functions
involved in remodeling of synaptic circuits, stress cascades, and visual behavior. Additionally,
we developed and made available an application-the CajaDB-to provide a friendly interface
for genomic, expression, and alternative splicing data of marmosets together with a series of
functionalities that allow the exploration of these data. CajaDB is available at
cajadb.neuro.ufrn.br.
CONCLUSION: The data point to differences in gene expression of male and female
common marmosets in all tissues analyzed. In frontal cortex, female-biased expression in
synaptic plasticity, stress, and visual processing might be linked to biological and behavioral
mechanisms of this sex. Due to the limited sample size, the data here analyzed are for
exploratory purposes.
Keywords: Adaptive strategies. Database. Neuropsychiatric primate model. Sexual
dimorphism. Synaptic plasticity. Transcriptomics.
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URI: https://repositorio.ufrn.br/jspui/handle/123456789/26430
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Costa CKL, Spyrides MHC, Sousa MBC. Consistency of three different questionnaires for evaluating sexual function in healthy young women. BMC Womens Health, 2018;18(1):204 doi: 10.1186/s12905-018-0693-y
Consistency of three different questionnaires for evaluating sexual function in healthy
young women
Abstract
BACKGROUND: Most studies on female sexual dysfunction are performed in population
inventories and under specific clinical conditions. These approaches are performed using
validated psychometric scales. Different scales to assess sexual function use different
numbers of questions to characterize their domains. They also may or may not include
domains of interaction between sexual partners. The objective of this study was to compare
the precision between scales to be able to analyze their accuracy for better diagnosis of sexual
dysfunction.
METHODS: Fifty (50) healthy young women were enrolled in this study. Three
questionnaires (FSFI, SQ-F, and GRISS) were applied to assess sexual function (n = 44). The
accuracy measured by the area under the ROC curve (AUC) for individual domains and to
cross-validated pairwise comparison of the three analyzed instruments was used. Kruskall-
Wallis test to analyze individual domains of the scales was also used.The P-value was
established as 0.05.
RESULTS: The results showed that all domains and total FSFI and GRISS scores were
significantly different between normal and dysfunctional women, but not for SQ-F domains.
Indeed, AUC accuracy varied from excellent-good domain discrimination for FSFI and
GRISS, but fair-poor for SQ-F. For the paired comparison between the three questionnaires a
fair accuracy was detected. The specificity percentage was around 84% whereas that for
sensibility was low, around 30%.
CONCLUSIONS: The best agreement was between FSFI and SQ-F, probably being related to
high similar shared questions when compared to GRISS. The agreement between SQ-F and
GRISS was low possible due to low number of questions in SQ-F to characterize similar
domains. This study evidenced high agreement between scales to sensitivity and low
agreement for specificity, thereby conferring fair accuracy between them. Thus, the limited
grade for discriminatory capacity (AUC) for sexual response should be considered when
comparing results from these three different questionnaires and also when comparing with
other different scales. In addition, despite the diversity of scales, the high reliability and fit for
14
their desire domain suggest that the FSFI scale has good accuracy for the current clinical
assessment of women's sexual health.
Keywords: Female sexual function. Psychometric scales accuracy. Couple relationships.
Primary diagnosis of dysfunction.
URI: https://repositorio.ufrn.br/jspui/handle/123456789/26431
15
Assis GG, Gasanov EV, Sousa MBC, Kozacz A, Murawska-Cialowicz E. Brain derived neutrophic factor, a link of aerobic metabolism to neuroplasticity. J Physiol Pharmacol., 2018;69(3). doi: 10.26402/jpp.2018.3.12
Brain derived neutrophic factor, a link of aerobic metabolism to neuroplasticity
Abstract
Currently, literature has accumulated great knowledge over the effect of exercise on the
neurotrophin named brain derived neurotrophic factor (BDNF) and its role in neuronal
plasticity. However, there is no enough discussion about how the exercise is related to
enrichment of BDNF in specific metabolic properties. This review provides the current
evidences regarding aerobic metabolism relation to BDNF concentrations in healthy
individuals. A PICOS strategy was applied considering the mesh terms for: P - healthy
subjects; I - physical exercise; C - aerobic metabolism demands; O - BDNF concentrations; S
- before and after aerobic exercise; on PubMed, Scopus and Medline databases. Studies
presenting at least one session the exercise with reports of BDNF analysis before and after
were included. Reviews, letters, case-reports, articles not written in English, non- published or
involving non-healthy populations were excluded. Compiling results, it was possible to
observe a close interaction between different aerobic energy demands from the exercise
models and the responses of BDNF, suggesting thus that increases in BDNF concentrations
are associated to the amount of aerobic energy required by exercise in a dose-dependent
manner. Moreover, the dynamics of BDNF synthesis and reuptake resemble the functioning
of the metabolic systems of aerobic energy generation, with which they share a co-
transcriptional factor dependence.
Keywords: Brain derived neurotrophic factor. Aerobic metabolism. Aerobic exercise.
Neuroplasticity. Prolonged exercise. Proliferator-activated receptor gamma co-activator 1-
alpha.
URI: https://repositorio.ufrn.br/jspui/handle/123456789/26432
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Branco PR, Araújo GS, Barrera J, Suarez-Kurtz G, Souza SJ. Uncovering association networks through an eQTL analysis involving human miRNAs and lincRNAs. Sci Rep., 2018;8(1):15050. doi: 10.1038/s41598-018-33420-z
Uncovering association networks through an eQTL analysis involving human miRNAs
and lincRNAs
Abstract
Non-coding RNAs (ncRNA) have an essential role in the complex landscape of human
genetic regulatory networks. One area that is poorly explored is the effect of genetic
variations on the interaction between ncRNA and their targets. By integrating a significant
amount of public data, the present study cataloged the vast landscape of the regulatory effect
of microRNAs (miRNA) and long intergenic noncoding RNAs (lincRNA) in the human
genome. An expression quantitative trait loci (eQTL) analysis was used to identify genetic
variants associated with miRNA and lincRNA and whose genotypes affect gene expression.
Association networks were built for eQTL associated to traits of clinical and/or
pharmacological relevance.
URI: https://repositorio.ufrn.br/jspui/handle/123456789/26433
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Pinheiro DML, Oliveira AHS, Coutinho LG, Fontes FL, Medeiros Oliveira RK, Oliveira TT, et al. Resveratrol decreases the expression of genes involved in inflammation through transcriptional regulation. Free Radic Biol Med., 2018;130:8-22. doi: 10.1016/j.freeradbiomed.2018.10.432
Resveratrol decreases the expression of genes involved in inflammation through
transcriptional regulation
Abstract
Oxidative stress generated during inflammation is associated with a wide range of
pathologies. Resveratrol (RESV) displays anti-inflammatory and antioxidant activities, being
a candidate for the development of adjuvant therapies for several inflammatory diseases.
Despite this potential, the cellular responses induced by RESV are not well known. In this
work, transcriptomic analysis was performed following lipopolysaccharide (LPS) stimulation
of monocyte cultures in the presence of RESV. Induction of an inflammatory response was
observed after LPS treatment and the addition of RESV led to decreases in expression of the
inflammatory mediators, tumor necrosis factor-alpha (TNF-α), interleukin-8 (IL-8), and
monocyte chemoattractant protein-1 (MCP-1), without cytotoxicity. RNA sequencing
revealed 823 upregulated and 2098 downregulated genes (cutoff ≥2.0 or ≤-2.0) after RESV
treatment. Gene ontology analysis showed that the upregulated genes were associated with
metabolic processes and the cell cycle, consistent with normal cell growth and differentiation
under an inflammatory stimulus. The downregulated genes were associated with
inflammatory responses, gene expression, and protein modification. The prediction of master
regulators using the iRegulon tool showed nuclear respiratory factor 1 (NRF1) and GA-
binding protein alpha subunit (GABPA) as the main regulators of the downregulated genes.
Using immunoprecipitation and protein expression assays, we observed that RESV was able
to decrease protein acetylation patterns, such as acetylated apurinic/apyrimidinic
endonuclease-1/reduction-oxidation factor 1 (APE1/Ref-1), and increase histone methylation.
In addition, reductions in p65 (nuclear factor-kappa B (NF-κB) subunit) and lysine-specific
histone demethylase-1 (LSD1) expression were observed. In conclusion, our data indicate that
treatment with RESV caused significant changes in protein acetylation and methylation
patterns, suggesting the induction of deacetylase and reduction of demethylase activities that
mainly affect regulatory cascades mediated by NF-кB and Janus kinase/signal transducers and
activators of transcription (JAK/STAT) signaling. NRF1 and GABPA seem to be the main
regulators of the transcriptional profile observed after RESV treatment.
18
Keywords: Resveratrol. Inflammation. RNAseq. Chromatin. Transcription.
URI: https://repositorio.ufrn.br/jspui/handle/123456789/26434
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Rennó-Costa C, Silva ACC, Blanco W, Ribeiro S. Computational models of memory consolidation and long-term synaptic plasticity during sleep. Neurobiol Learn Mem., 2018;(18):30239-9. doi: 10.1016/j.nlm.2018.10.003
Computational models of memory consolidation and long-term synaptic plasticity
during sleep
Abstract
The brain stores memories by persistently changing the connectivity between neurons. Sleep
is known to be critical for these changes to endure. Research on the neurobiology of sleep and
the mechanisms of long-term synaptic plasticity has provided data in support of various
theories of how brain activity during sleep affects long-term synaptic plasticity. The
experimental findings – and therefore the theories – are apparently quite contradictory, with
some evidence pointing to a role of sleep in the forgetting of irrelevant memories, whereas
other results indicate that sleep supports the reinforcement of the most valuable recollections.
A unified theoretical framework is in need. Computational modeling and simulation provide
grounds for the quantitative testing and comparison of theoretical predictions and observed
data, and might serve as a strategy to organize the rather complicated and diverse pool of data
and methodologies used in sleep research. This review article outlines the emerging progress
in the computational modeling and simulation of the main theories on the role of sleep in
memory consolidation.
Keywords: Homeostasis. Sequential. Replay. Active consolidation. Embossing. Down-
scaling. Up-scaling. Simulation. LTP. LTD.
URI: https://repositorio.ufrn.br/jspui/handle/123456789/26048
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Mota NB, Sigman M, Cecchi G, Copelli M, Ribeiro S. The maturation of speech structure in psychosis is resistant to formal education. npj Schizophrenia, 2018;4(1):25. doi: 10.1038/s41537-018-0067-3
The maturation of speech structure in psychosis is resistant to formal education
Abstract
Discourse varies widely with age, level of education, and psychiatric state. Word graphs have
been recently shown to provide behavioral markers of formal thought disorders in psychosis
(e.g., disorganized flow of ideas) and to track literacy acquisition in children with typical
development. Here we report that a graph-theoretical computational analysis of verbal reports
from subjects spanning 6 decades of age and 2 decades of education reveals asymptotic
changes over time that depend more on education than age. In typical subjects, short-range
recurrence and lexical diversity stabilize after elementary school, whereas graph size and
long-range recurrence only steady after high school. Short-range recurrence decreases towards
random levels, while lexical diversity, long-range recurrence, and graph size increase away
from near-randomness towards a plateau in educated adults. Subjects with psychosis do not
show similar dynamics, presenting at adulthood a children-like discourse structure. Typical
subjects increase the range of word recurrence over school years, but the same feature in
subjects with psychosis resists education.
URI: https://repositorio.ufrn.br/jspui/handle/123456789/26290
21
Ribeiro S. Decifrar o enigma da política de drogas requer mais ciência do que nunca. Ciência e Cultura, 2018;70(3):51-52. doi: 10.21800/2317-66602018000300013
Decifrar o enigma da política de drogas requer mais ciência do que nunca
URI: https://repositorio.ufrn.br/jspui/handle/123456789/26435