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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

https://repositorio.ufrn.br/jspui/handle/123456789/25929

https://doi.org/10.7717/peerj.5678

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.



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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.

https://dx.doi.org/10.1590/1516-4446-2018-0140

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9

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.



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



https://doi.org/10.1016/j.ygcen.2018.07.016

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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13

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

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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.



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.



16

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.



17

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.

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Keywords: Resveratrol. Inflammation. RNAseq. Chromatin. Transcription.



19

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.



20

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.



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



https://dx.doi.org/10.21800/2317-66602018000300013

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