37 research outputs found
AP2γ: a new player on adult hippocampal neurogenesis regulation
Since the recognition that the mammalian brain retains the ability to generate newborn neurons with functional relevance throughout life, the matrix of molecular regulators that govern adult neurogenesis has been the focus of much interest. In a recent study published in Molecular Psychiatry, we demonstrate Activating Protein 2γ (AP2γ), a transcription factor previously implicated in cell fate determination in the developing cortex, as a novel player in the regulation of glutamatergic neurogenesis in the adult hippocampus. Using distinct experimental approaches, we showed that AP2γ is specifically present in a subpopulation of transient amplifying progenitors, where it acts as a crucial promoter of proliferation and differentiation of adult-born glutamatergic granule neurons. Strikingly, deficiency of AP2γ in the adult brain compromises the generation of new glutamatergic neurons, with impact on the function of cortico-limbic circuits. Here, we share our view on how AP2γ integrates the transcriptional orchestration of glutamatergic neurogenesis in the adult hippocampus, and consequently, how it emerges as a novel molecular candidate to study the translation of environmental pressures into alterations of brain neuroplasticity in homeostatic, but also in neuropathological contexts.Bial Foundation (427/14); Northern Portugal Regional Operational Programme (NORTE
2020); European Regional Development Fund (FEDER) (projects NORTE-01-0145-FEDER-000013 e NORTE-01-0145-FEDER-000023); Competitiveness Factors Operational Programme (COMPETE)info:eu-repo/semantics/publishedVersio
Collisionless kinetic theory of rolling molecules
We derive a collisionless kinetic theory for an ensemble of molecules
undergoing nonholonomic rolling dynamics. We demonstrate that the existence of
nonholonomic constraints leads to problems in generalizing the standard methods
of statistical physics. In particular, we show that even though the energy of
the system is conserved, and the system is closed in the thermodynamic sense,
some fundamental features of statistical physics such as invariant measure do
not hold for such nonholonomic systems. Nevertheless, we are able to construct
a consistent kinetic theory using Hamilton's variational principle in
Lagrangian variables, by regarding the kinetic solution as being concentrated
on the constraint distribution. A cold fluid closure for the kinetic system is
also presented, along with a particular class of exact solutions of the kinetic
equations.Comment: Revised version; 31 pages, 1 figur
Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system
Oligodendrocytes have been considered as a functionally homogeneous population in the central nervous system (CNS). We performed single-cell RNA sequencing on 5072 cells of the oligodendrocyte lineage from 10 regions of the mouse juvenile and adult CNS. Thirteen distinct populations were identified, 12 of which represent a continuum from Pdgfra(+) oligodendrocyte precursor cells (OPCs) to distinct mature oligodendrocytes. Initial stages of differentiation were similar across the juvenile CNS, whereas subsets of mature oligodendrocytes were enriched in specific regions in the adult brain. Newly formed oligodendrocytes were detected in the adult CNS and were responsive to complex motor learning. A second Pdgfra(+) population, distinct from OPCs, was found along vessels. Our study reveals the dynamics of oligodendrocyte differentiation and maturation, uncoupling them at a transcriptional level and highlighting oligodendrocyte heterogeneity in the CNS
Classes and continua of hippocampal CA1 inhibitory neurons revealed by single-cell transcriptomics
Understanding any brain circuit will require a categorization of its constituent neurons. In hippocampal area CA1, at least 23 classes of GABAergic neuron have been proposed to date. However, this list may be incomplete; additionally, it is unclear whether discrete classes are sufficient to describe the diversity of cortical inhibitory neurons or whether continuous modes of variability are also required. We studied the transcriptomes of 3,663 CA1 inhibitory cells, revealing 10 major GABAergic groups that divided into 49 fine-scale clusters. All previously described and several novel cell classes were identified, with three previously described classes unexpectedly found to be identical. A division into discrete classes, however, was not sufficient to describe the diversity of these cells, as continuous variation also occurred between and within classes. Latent factor analysis revealed that a single continuous variable could predict the expression levels of several genes, which correlated similarly with it across multiple cell types. Analysis of the genes correlating with this variable suggested it reflects a range from metabolically highly active faster-spiking cells that proximally target pyramidal cells to slower-spiking cells targeting distal dendrites or interneurons. These results elucidate the complexity of inhibitory neurons in one of the simplest cortical structures and show that characterizing these cells requires continuous modes of variation as well as discrete cell classes.</p
Regional Innovation and Research Policy Outlook: Policy Practices in Eight European Regions
This publication is part of a project called 'Practical Regional Research and Innovation policy in Action. The Efficient Tools for Regional Catching-up in New Member States'
Evidence-based psychotherapeutic interventions for young people with mental disorders : a systematic review
INTRODUCTION: Young People (YP) with mental disorders have the
highest rates of long-term morbidity and mortality. Mental disorders increase markably in young adulthood: 75% of mental disorders emerge before the age of 25 years but less than half of YP receive appropriate treatment. Recognizing this public health concern, the European Cooperation in Science and Technology
(COST) funded the “European Network of Individualized Psychotherapy Treatment of Young People with Mental Disorders”
(TREATme).OBJECTIVES: To conduct systematic literature reviews elucidating
the efficacy of psychotherapeutic interventions for YP diagnosed
with mental disorders.[excerpt]peer-reviewe
Evidence-based psychotherapeutic interventions for young people with substance use disorder : a systematic literature review.
INTRODUCTION: Substance use disorders (SUD) are a global problem
with many health and economic consequences, impacting the user,
the mental health system and society at large. Over half of SUD
problems begin during adolescence. Treatment approaches and
effective management frequently involve psychotherapeutic interventions, which prevents long term morbidity and mortality. Recognizing this public health concern and the need for more empirical
based knowledge, the European Cooperation in Science and Technology (COST) funded the ‘European Network of Individualized
Psychotherapy Treatment of Young People with Mental Disorders’
(TREATme).OBJECTIVES: As part of the aims of TREATme, in this particular
study a systematic review of the published literature was conducted
to determine the effectiveness of specific psychotherapeutic interventions (PI) in young people (YP) with SUDs.[excerpt]peer-reviewe
Origin, fate and dynamics of macrophages at central nervous system interfaces.
Perivascular, subdural meningeal and choroid plexus macrophages are non-parenchymal macrophages that mediate immune responses at brain boundaries. Although the origin of parenchymal microglia has recently been elucidated, much less is known about the precursors, the underlying transcriptional program and the dynamics of the other macrophages in the central nervous system (CNS). It was assumed that they have a high turnover from blood-borne monocytes. However, using parabiosis and fate-mapping approaches in mice, we found that CNS macrophages arose from hematopoietic precursors during embryonic development and established stable populations, with the notable exception of choroid plexus macrophages, which had dual origins and a shorter life span. The generation of CNS macrophages relied on the transcription factor PU.1, whereas the MYB, BATF3 and NR4A1 transcription factors were not required