TY - JOUR T1 - A Novel Activator of CBP/p300 Acetyltransferases Promotes Neurogenesis and Extends Memory Duration in Adult Mice JF - The Journal of Neuroscience JO - J. Neurosci. SP - 10698 LP - 10712 DO - 10.1523/JNEUROSCI.5772-12.2013 VL - 33 IS - 26 AU - Snehajyoti Chatterjee AU - Pushpak Mizar AU - Raphaelle Cassel AU - Romain Neidl AU - B. Ruthrotha Selvi AU - Dalvoy Vasudevarao Mohankrishna AU - Bhusainahalli M. Vedamurthy AU - Anne Schneider AU - Olivier Bousiges AU - Chantal Mathis AU - Jean-Christophe Cassel AU - Muthusamy Eswaramoorthy AU - Tapas K. Kundu AU - Anne-Laurence Boutillier Y1 - 2013/06/26 UR - http://www.jneurosci.org/content/33/26/10698.abstract N2 - Although the brain functions of specific acetyltransferases such as the CREB-binding protein (CBP) and p300 have been well documented using mutant transgenic mice models, studies based on their direct pharmacological activation are still missing due to the lack of cell-permeable activators. Here we present a small-molecule (TTK21) activator of the histone acetyltransferases CBP/p300, which, when conjugated to glucose-based carbon nanosphere (CSP), passed the blood–brain barrier, induced no toxicity, and reached different parts of the brain. After intraperitoneal administration in mice, CSP-TTK21 significantly acetylated histones in the hippocampus and frontal cortex. Remarkably, CSP-TTK21 treatment promoted the formation of long and highly branched doublecortin-positive neurons in the subgranular zone of the dentate gyrus and reduced BrdU incorporation, suggesting that CBP/p300 activation favors maturation and differentiation of adult neuronal progenitors. In addition, mRNA levels of the neuroD1 differentiation marker and BDNF, a neurotrophin required for the terminal differentiation of newly generated neurons, were both increased in the hippocampus concomitantly with an enrichment of acetylated-histone on their proximal promoter. Finally, we found that CBP/p300 activation during a spatial training, while not improving retention of a recent memory, resulted in a significant extension of memory duration. This report is the first evidence for CBP/p300-mediated histone acetylation in the brain by an activator molecule, which has beneficial implications for the brain functions of adult neurogenesis and long-term memory. We propose that direct stimulation of acetyltransferase function could be useful in terms of therapeutic options for brain diseases. ER -