Environmental Enrichment Increased Bdnf Transcripts in the Prefrontal Cortex: Implications for an Epigenetically Controlled Mechanism.

Environmental enrichment (EE) is a condition characterized by its complexity regarding social contact, exposure to novelty, tactile stimuli and voluntary exercise, also is considered as a eustress model. The impact of EE on brain physiology and behavioral outcomes may be at least partly underpinned by mechanisms involving the modulation of the brain-derived neurotrophic factor (BDNF), but the connection between specific Bdnf exon expression and their epigenetic regulation remain poorly understood. This study aimed to dissect the transcriptional and epigenetic regulatory effect of 54-day exposure to EE on BDNF by analysing individual BDNF exons mRNA expression and the DNA methylation profile of a key transcriptional regulator of the Bdnf gene, exon IV, in the prefrontal cortex (PFC) of C57BL/6 male mice (sample size = 33). Bdnf exons II, IV, VI and IX mRNA expression were upregulated and methylation levels at two CpG sites of exon IV were reduced in the PFC of EE mice. As deficit in exon IV expression has also been causally implicated in stress-related psychopathologies, we also assessed anxiety-like behavior and plasma corticosterone levels in these mice to determine any potential correlation. However, no changes were observed in EE mice. The findings may suggest an EE-induced epigenetic control of BDNF exon expression via a mechanism involving exon IV methylation. The findings of this study contribute to the current literature by dissecting the Bdnf gene topology in the PFC where transcriptional and epigenetic regulatory effect of EE takes place.

Efeitos do metilfenidato sobre as glândulas salivares maternas de camundongos / Methylphenidate effects on maternal salivary glands of mice

Introdução: O metilfenidato (MFD) é um derivado anfetamínico estimulante do sistema nervoso central, que vem sendo cada vez mais consumido pela população mundial, incluindo as mulheres em idade fértil. Ainda não foram estabelecidos os efeitos deste medicamento nas glândulas salivares, durante a gestação. Objetivo: Identificar alterações histomorfológicas em glândulas salivares maternas expostas ao metilfenidato. Material e método: Para análise histológica, foram utilizadas 32 fêmeas de camundongos Swiss prenhes, distribuídas em um grupo controle e um grupo tratado. A administração foi realizada do quinto ao 17º dia de gestação, via injeção subcutânea; o grupo tratado recebeu 5 mg/kg de metilfenidato, enquanto o grupo controle recebeu o mesmo volume de solução salina estéril. As fêmeas foram eutanasiadas e tiveram suas glândulas salivares removidas e incluídas em parafina para análise em microscopia óptica. Para avaliar a associação entre as variáveis dos grupos, o teste de Kolmogorov-Smirnov e o teste T foram utilizados. Resultado: As glândulas parótidas do grupo tratado apresentaram alterações no raio dos ductos e na quantidade de ácinos, quando comparadas às glândulas parótidas do grupo controle. A glândula submandibular do grupo tratado foi a mais afetada: mostrou diferença estatisticamente significativa na espessura da parede dos ductos secretores, no raio dos ductos e no raio dos ácinos, quando comparada à glândula submandibular do grupo controle. A glândula sublingual não apresentou alterações significativas. Conclusão: Neste delineamento experimental, o metilfenidato apresentou-se como agente indutor de alterações morfológicas das glândulas salivares, promovendo alterações significativas nos raios de ductos e ácinos das mesmas, sendo a glândula submandibular a mais susceptível a este fármaco.

Introduction: Methylphenidate (MFD) is a stimulant amphetamine derivative of the central nervous system, which is being increasingly consumed by the world population, including women of childbearing age. It has not yet established the effects of this medicine in the salivary glands during pregnancy. Objective: Evaluate the exposure effects to the MPD in the maternal salivary glands. Material and method: For prenatal study, 32 pregnant female Swiss mice were used, divided into a control and a treated group. The treated group received 5 mg/kg of MPD via subcutaneous injection from the 5th to the 17th day and the control received sterile saline in the same volume and pregnancy period. Females were euthanized and had their salivary glands removed and embedded in paraffin for analysis in optical microscopy. To evaluate the association between the variables of the groups, the Kolmogorov-Smirnov test and and T test were used. Result: The parotid glands of the treated group showed statistically significant change within the ducts and the amount of acini when compared to the control group. The submandibular gland was the most affected, it showed a difference statistically significant in wall thickness of the secretory ducts, within the ducts and within the acini when compared to the control group. The sublingual gland showed no significant changes. Conclusion: In this experiment methylphenidate is presented as inducing agent morphological changes of the salivary glands, promoting significant changes in ducts radii and acini, submandibular gland being more susceptible to this drug.