A novel mechanism regulating cortical plasticity

GABA is the chief inhibitory neurotransmitter in the mammalian central nervous system. Several studies have demonstrated that GABA plays a critical role in shaping cortical circuits during early postnatal development as, while GABA is an inhibitory transmitter in the mature brain, its action is primarily excitatory during early brain development.  

In this study, Deidda et al. show that a brief alteration in the excitatory action of GABA during early development can impair plasticity in the visual cortex later in development, and this effect is mediated by brain-derived neurotrophic factor (BDNF). BDNF is a secreted protein that is found in the brain and the periphery where it supports the survival of neurons and the growth of new ones.


Early depolarizing GABA controls critical period plasticity in the rat visual cortex.
Deidda G., Allegra M., Cerri C., Naskar S., Bony G., Zunino G., Bozzi Y.,  Caleo M., Cancedda L.
Nature Neuroscience, in press (2014).


Neurofibromin deficiency in a mouse model of autism  

Autism belongs to a heterogeneous group of diseases primarily characterized by deficits in social behaviors. Recent studies suggest that multiple genetic defects concur in autism to disrupt the formation and function of brain circuits during embryonic and postnatal development, leading to a varying range of cognitive dysfunctions. Autism symptoms are also present in patients affected by neurological diseases of known genetic origin, such as Rett’s syndrome, Fragile X syndrome and neurofibromatosis.

In this study, Provenzano et al. show that mice bearing a mutation in the En2 gene present learning deficits accompanied by a marked down regulation of neurofibromin, the causative gene of neurofibromatosis. These results demonstrate that multiple genetic defects contribute to cognitive deficits in a mouse model of autism.


Hippocampal dysregulation of neurofibromin-dependent pathways is associated with impaired spatial learning in Engrailed 2 knockout mice.
Provenzano G., Pangrazzi L., Poli A., Sgadò P., Genovesi S., Zunino G., Berardi N., Casarosa S., Bozzi Y.
The Journal of Neuroscience, 1 October 2014, 34(40): 13281-13288
doi: 10.1523/JNEUROSCI.2894-13.2014.


Transcriptome profiling in Engrailed2 knockout mice reveals common molecular pathways associated with ASD

Sgadò P, Provenzano G, Dassi E, Adami V, Zunino G, Genovesi S, Casarosa S, Bozzi Y (2013)

Molecular Autism, 4:51  doi:10.1186/2040-2392-4-51

Transcriptome analysis has been used in autism spectrum disorder (ASD) to unravel common pathogenic pathways based on the assumption that distinct rare genetic variants or epigenetic modifications affect common biological pathways. We performed a transcriptome profiling of the cerebellum and hippocampus of En2 mutant mice, a model for ASD. Our functional analysis revealed that the molecular signature of En2 mutant cerebellum and hippocampus shares convergent pathological pathways with ASD, confirming that En2 mutant mice are valuable tool to investigate molecular alterations related to ASD.


Punctuated Evolution of Prostate Cancer Genomes

Sylvan C. Baca, Davide Prandi, Michael S. Lawrence, Juan Miguel Mosquera, Alessandro Romanel,Yotam Drier, Kyung Park, Naoki Kitabayashi, Theresa Y. MacDonald, Mahmoud Ghandi, Eliezer Van Allen, Gregory V. Kryukov, Andrea Sboner, Jean-Philippe Theurillat, T. David Soong, Elizabeth Nickerson, Daniel Auclair, Ashutosh Tewari, Himisha Beltran, Robert C. Onofrio, Gunther Boysen, Candace Guiducci, Christopher E. Barbieri, Kristian Cibulskis, Andrey Sivachenko, Scott L. Carter, Gordon Saksena, Douglas Voet, Alex H Ramos, Wendy Winckler, Michelle Cipicchio, Kristin Ardlie, Philip W. Kantoff, Michael F. Berger, Stacey B. Gabriel, Todd R. Golub, Matthew Meyerson, Eric S. Lander, Olivier Elemento, Gad Getz, Francesca Demichelis*, Mark A. Rubin*, Levi A. Garraway*

Cell, 25 April, 2013, Volume 153, Issue 3

The characterization of the clonal hierarchy of genomic lesions in prostate tumors charted the path of oncogenic events that may drive prostate carcinogenesis through interdependent genomic structural rearrangements named chromoplexy.  Chromoplexy accounts for the co-ordinated dysregulation of multiple prostate cancer genes leading to cancer evolution in relatively few events.


Single-Cell Imaging of HIV-1 Provirus (SCIP)

Cristina Di Primio, Valentina Quercioli, Awatef Allouchb, Rik Gijsbersc, Frauke Christc, Zeger Debyserc, Daniele Arosio and Anna Cereseto

PNAS, April 2, 2013, vol. 110, no. 14. p. 5636–5641 www.pnas.org/cgi/doi/10.1073/pnas.1216254110

SCIP, Single-Cell Imaging of HIV-1Provirus, is an imaging technique to efficiently visualize HIV-1 DNA integrated into the host genome of individual cells. The possibility to analyze viral integrated DNA within structurally intact nuclei of individual cells allows studying the topology of HIV-1 in the nuclear compartment and provides the possibility to individually track integrated-viral DNA within the nuclei of infected cells. The power of SCIP to monitor expression /integration in individual cells might be key to investigate the still obscure mechanisms leading to HIV-1 latency and to screen for HIV-1 potential cofactors and antiretroviral drugs.