Il cervello dal di dentro

The functional magnetic resonance imaging (fMRI) techniques are a potent probe able to visualize brain functions, by analyzing modification of blood oxygenation, and see the action in specific brain areas in response to activity or thoughts. fMRI thus promise to be a formidable tool not only to draw a new cartography of brain functional areas, but also a new tool to understand some aspects of brain function’s evolution, as well to get insights and to breach the wall into cognition, morality and consciousness. Nevertheless fMRI is not deprived of pitfalls such as limitation in spatial accuracy, reliable reproducibility of brain scan amongst different individuals or in the same person at different stages of life ( age or health versus disease), the different time scale of fMRI measurements (seconds) and neuron’s action potentials (milliseconds). Thus often caution is required in the appreciation of fMRI results and conclusions, that could lead to incorrect interpretation of brain signals and induce to draw spurious conclusions. New applications combining fMRI and real time visualization of one's own brain activity in healthy volunteers or patients promise to enable individuals to modify brain response and thus therapeutically or with other goals intervene in modifying individual behaviors. Specially this last aspect, as well as the concern about the confidentiality and storage of sensible information or forensic uses of such approaches, raises the problem of mind privacy and new ethical questions

The serotonin receptor 7 and the structural plasticity of brain circuits

Serotonin (5-hydroxytryptamine, 5-HT) modulates numerous physiological processes in the nervous system. Together with its function as neurotransmitter, 5-HT regulates neurite outgrowth, dendritic spine shape and density, growth cone motility and synapse formation during development. In the mammalian brain 5-HT innervation is virtually ubiquitous and the diversity and specificity of its signaling and function arise from at least 20 different receptors, grouped in 7 classes. Here we will focus on the role 5-HT7 receptor (5-HT7R) in the correct establishment of neuronal cytoarchitecture during development, as also suggested by its involvement in several neurodevelopmental disorders. The emerging picture shows that this receptor is a key player contributing not only to shape brain networks during development but also to remodel neuronal wiring in the mature brain, thus controlling cognitive and emotional responses. The activation of 5-HT7R might be one of the mechanisms underlying the ability of the CNS to respond to different stimuli by modulation of its circuit configuration

Enhancement of Dopaminergic Differentiation in Proliferating Midbrain Neuroblasts by Sonic Hedgehog and Ascorbic Acid

We analyzed the molecular mechanisms involved in the acquisition and maturation of dopaminergic (DA) neurons generated in vitro from rat ventral mesencephalon (MES) cells in the presence of mitogens or specific signaling molecules. The addition of basic fibroblast growth factor (bFGF) to MES cells in serum-free medium stimulates the proliferation of neuroblasts but delays DA differentiation. Recombinant Sonic hedgehog (SHH) protein increases up to three fold the number of tyrosine hydroxylase (TH)-positive cells and their differentiation, an effect abolished by anti-SHH antibodies. The expanded cultures are rich in nestin-positive neurons, glial cells are rare, all TH+ neurons are DA, and all DA and GABAergic markers analyzed are expressed. Adding ascorbic acid to bFGF/SHH-treated cultures resulted in a further five- to seven-fold enhancement of viable DA neurons. This experimental system also provides a powerful tool to generate DA neurons from single embryos. Our strategy provides an enriched source of MES DA neurons that are useful for analyzing molecular mechanisms controlling their function and for experimental regenerative approaches in DA dysfunction

Transcription factor KLF7 regulates differentiation of neuroectodermal and mesodermal cell lineages

Previous gene targeting studies in mice have implicated the nuclear protein Krüppel-like factor 7 (KLF7) in nervous system development while cell culture assays have documented its involvement in cell cycle regulation. By employing short hairpin RNA (shRNA)-mediated gene silencing, here we demonstrate that murine Klf7 gene expression is required for in vitro differentiation of neuroectodermal and mesodermal cells. Specifically, we show a correlation of Klf7 silencing with down-regulation of the neuronal marker microtubule-associated protein 2 (Map2) and the nerve growth factor (NGF) tyrosine kinase receptor A (TrkA) using the PC12 neuronal cell line. Similarly, KLF7 inactivation in Klf7-null mice decreases the expression of the neurogenic marker brain lipid-binding protein/fatty acid-binding protein 7 (BLBP/FABP7) in neural stem cells (NSCs). We also report that Klf7 silencing is detrimental to neuronal and cardiomyocytic differentiation of embryonic stem cells (ESCs), in addition to altering the adipogenic and osteogenic potential of mouse embryonic fibroblasts (MEFs). Finally, our results suggest that genes that are key for self-renewal of undifferentiated ESCs repress Klf7 expression in ESCs. Together with previous findings, these results provide evidence that KLF7 has a broad spectrum of regulatory functions, which reflect the discrete cellular and molecular contexts in which this transcription factor operates. © 2010 Elsevier Inc

Comparison of gene expression profile in embryonic mesencephalon and neuronal primary cultures

Peer reviewe

Lmx1a-Dependent Activation of miR-204/211 Controls the Timing of Nurr1-Mediated Dopaminergic Differentiation

The development of midbrain dopaminergic (DA) neurons requires a fine temporal and spatial regulation of a very specific gene expression program. Here, we report that during mouse brain development, the microRNA (miR-) 204/211 is present at a high level in a subset of DA precursors expressing the transcription factor Lmx1a, an early determinant for DA-commitment, but not in more mature neurons expressing Th or Pitx3. By combining different in vitro model systems of DA differentiation, we show that the levels of Lmx1a influence the expression of miR-204/211. Using published transcriptomic data, we found a significant enrichment of miR-204/211 target genes in midbrain dopaminergic neurons where Lmx1a was selectively deleted at embryonic stages. We further demonstrated that miR-204/211 controls the timing of the DA differentiation by directly downregulating the expression of Nurr1, a late DA differentiation master gene. Thus, our data indicate the Lmx1a-miR-204/211-Nurr1 axis as a key component in the cascade of events that ultimately lead to mature midbrain dopaminergic neurons differentiation and point to miR-204/211 as the molecular switch regulating the timing of Nurr1 expression

An underground Sagnac gyroscope with sub-prad/s rotation rate sensitivity: toward General Relativity tests on Earth

Measuring in a single location on Earth its angular rotation rate with respect to the celestial frame, with a sensitivity enabling access to the tiny Lense-Thirring effect is an extremely challenging task. GINGERINO is a large frame ring laser gyroscope, operating free running and unattended inside the underground laboratory of the Gran Sasso, Italy. The main geodetic signals, i.e., Annual and Chandler wobbles, daily polar motion and Length of the Day, are recovered from GINGERINO data using standard linear regression methods, demonstrating a sensitivity better than 1 prad/s, therefore close to the requirements for an Earth-based Lense-Thirring test.Comment: 7 pages, 5 figure

Erratum to: Constraining theories of gravity by GINGER experiment

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