Network Dynamics Mediate Circadian Clock Plasticity

A circadian clock governs most aspects of mammalian behavior. Although its properties are in part genetically determined, altered light-dark environment can change circadian period length through a mechanism requiring de novo DNA methylation. We show here that this mechanism is mediated not via cell-autonomous clock properties, but rather through altered networking within the suprachiasmatic nuclei (SCN), the circadian “master clock,” which is DNA methylated in region-specific manner. DNA methylation is necessary to temporally reorganize circadian phasing among SCN neurons, which in turn changes the period length of the network as a whole. Interruption of neural communication by inhibiting neuronal firing or by physical cutting suppresses both SCN reorganization and period changes. Mathematical modeling suggests, and experiments confirm, that this SCN reorganization depends upon GABAergic signaling. Our results therefore show that basic circadian clock properties are governed by dynamic interactions among SCN neurons, with neuroadaptations in network function driven by the environment

CROATIAN SOCIETY OF CLINICAL EMBRYOLOGISTS – GUIDELINES ON THE EPIDEMIOLOGICAL FRAMEWORK FOR THE IMPLEMENTATION OF MEDICALLY ASSISTED REPRODUCTION (MAR) PROCEDURES DURING THE COVID-19 PANDEMIC REGARDING THE SAFETY OF PATIENTS AND MEDICAL HEALTH WORKERS

Due to the high virulence of the SARS-CoV-2 virus, the infection rate in the community has led to a state of pandemic, leading to the introduction of new emergency measures all over the world. With the aim of controlling and preventing the SARS-CoV-2 viral epidemic, the health institutions performing medically assisted reproduction (MAR) suspended any new MAR treatments in order to reduce the burden on the health care system and implement current social distancing recommendations. Considering the favorable epidemiological situation in Croatia, our perspective is that it is time to conceive, plan and bring forth guidelines for restarting work in MAR centres, taking into account the selection of patients and organization of good laboratory and clinical practices with emphasis on the safety of patients and health workers. In regard to epidemiological knowledge, it is important to establish the reorganization of work in MAR centres including epidemiological measures of reducing unnecessary stays in closed spaces, the usage of protective gear by patients and health workers and disinfection of the working spaces and equipment

TET enzymes and DNA hydroxymethylation in neural development and function : how critical are they?

Epigenetic modifications of the genome play important roles in controlling gene transcription thus regulating several molecular and cellular processes. A novel epigenetic modification - 5-hydroxymethylcytosine (5hmC) - has been recently described and attracted a lot of attention due to its possible involvement in the active DNA demethylation mechanism. TET enzymes are dioxygenases capable of oxidizing the methyl group of 5-methylcytosines (5mC) and thus converting 5mC into 5hmC. Although most of the work on TET enzymes and 5hmC has been carried out in embryonic stem (ES) cells, the highest levels of 5hmC occur in the brain and in neurons, pointing to a role for this epigenetic modification in the control of neuronal differentiation, neural plasticity and brain functions. Here we review the most recent advances on the role of TET enzymes and DNA hydroxymethylation in neuronal differentiation and function.We apologize to those researchers whose important work we were not able to cite. We would like to thank all members of the Neurosciences Research Domain (ICVS) for useful discussions, in particular Luisa Pinto and Joao Oliveira for critically reading the manuscript. Our work is funded by the Fundacao para a Ciencia e Tecnologia (FCT, Portugal) and Compete Program with the project reference PTDC/BIA-BCM/121276/2010. C.J. Marques is the recipient of an FCT Investigator Starting Grant

BDNF Methylation and Maternal Brain Activity in a Violence-Related Sample

It is known that increased circulating glucocorticoids in the wake of excessive, chronic, repetitive stress increases anxiety and impairs Brain-Derived Neurotrophic Factor (BDNF) signaling. Recent studies of BDNF gene methylation in relation to maternal care have linked high BDNF methylation levels in the blood of adults to lower quality of received maternal care measured via self-report. Yet the specific mechanisms by which these phenomena occur remain to be established. The present study examines the link between methylation of the BDNF gene promoter region and patterns of neural activity that are associated with maternal response to stressful versus non-stressful child stimuli within a sample that includes mothers with interpersonal violence-related PTSD (IPV-PTSD). 46 mothers underwent fMRI. The contrast of neural activity when watching children-including their own-was then correlated to BDNF methylation. Consistent with the existing literature, the present study found that maternal BDNF methylation was associated with higher levels of maternal anxiety and greater childhood exposure to domestic violence. fMRI results showed a positive correlation of BDNF methylation with maternal brain activity in the anterior cingulate (ACC), and ventromedial prefrontal cortex (vmPFC), regions generally credited with a regulatory function toward brain areas that are generating emotions. Furthermore we found a negative correlation of BDNF methylation with the activity of the right hippocampus. Since our stimuli focus on stressful parenting conditions, these data suggest that the correlation between vmPFC/ACC activity and BDNF methylation may be linked to mothers who are at a disadvantage with respect to emotion regulation when facing stressful parenting situations. Overall, this study provides evidence that epigenetic signatures of stress-related genes can be linked to functional brain regions regulating parenting stress, thus advancing our understanding of mothers at risk for stress-related psychopathology