The Retrosplenial Cortex (RSC) has a persistent role in the establishment of spatial and contextual memory, with also the connections between visuo-spatial association cortices. The RSC’s ability to form afferent and efferent connections with the Parahippocampal areas of the brain allow it to be another prime location in the brains of both rodents and humans where multiple cues are linked together in memory formation, storage and retrieval of Long Term Memories. Due to the high nature of memory formation and retrieval, the RSC has become a section of the brain that in recent years has been more heavily focused on for the research of Alzheimer’s and Dementia. The RSC has not been examined fully in previous studies with examination of the expression of the apolipoprotein E (APOE) gene along with other genetic and regulatory factors. There are 3 major alleles of the APOE gene (APOE2, APOE3, and APOE4), with APOE4 having the greatest risk for AD. In this research, I identify the relative connection between DEK the proto-oncogene and APOE3 and APOE4 in a rodent model, looking specifically at the RSC and how it affects spatial memory with an induced model of chronic stress.
Overnight, room temperature hold
(ONH) of whole blood before component processing
offers several benefits. This study evaluated the storage
and in vivo recovery characteristics of ONH red blood
cells (RBCs) stored in additive solution-7 (AS-7).
Wu et al. map an Nf1-Stat3-Arid1b/ b-catenin pathway that initiates
Neurofibromatosis type 1 (Nf1) neurofibromas, using unbiased
insertional mutagenesis screening. Stat3 transcriptionally represses Gsk3b and Arid1b, thereby activating b-catenin in Schwann cell precursors and resulting in neurofibroma initiation and maintenance.
Stat3-mediated modification plays a role in early tumorigenesis.
PM-18. EGFR-STAT3 ACTIVATES b-CATENIN SIGNALING TO
DRIVE NEUROFIBROMA INITIATION IN NF1, AND PLAYS A
ROLE IN TUMOR MAINTENANCE
Nancy Ratner1, Vincent Keng2, Deanna M. Patmore1, Jed K. Kendall1,
Edwin Jousma1, Kwangmin Choi1, Danhua Fan2, Eric B. Schwartz2, James
R. Fuchs2, Yuanshu Zou2, Mi-Ok Kim1, Eva Dombi5, David E. Levy6, Jose
A. Cancelas1, Anat Stemmer-Rachamimov4, Robert J. Spinner3, and David
Cincinnati Children’s, Cincinnati, OH, USA; 2
Minnesota, Minneapolis, MN, USA; 3
Mayo Clinic, Rochester, MN, USA; 4
Massachusetts General Hospital, Boston, MA, USA; 5
Institute Pediatric Branch, Bethesda, MD, USA; 6
New York University School
of Medicine, New York, NY, USA
To identify genes and signaling pathways that drive peripheral nerve tumor
initiationand growth beyond the Ras-MAPK pathwaywe used unbiased insertional
mutagenesis screening. We identified Stat3 as a potential driver of
Neurofibromatosis type 1 neurofibroma. Targeted genetic deletion of Stat3
in Schwann cell precursors (SCPs) and Schwann cells (SCs) largely prevented
neurofibroma formation, and self-renewal of tumor initiating cells. Genetic
gain- and loss-of-function identified EGFR as the major upstream regulator
of P-Stat3 in mouse and human neurofibroma SCP and in neurofibroma initiation;
IL-6 reinforced EGFR/Jak/Stat signaling. Preclinical tests of a Jak2/
Stat3 inhibitor reduced established neurofibroma growth, supporting an additional
role for Stat3 in benign nerve tumor maintenance. Unexpectedly, downstream
of Stat3, we identified b-catenin, and b-catenin expression rescued
phenotypic effects of Stat3 loss in SCPs. Phosphorylated STAT3 (Y705) and
b-catenin were strongly correlated in NF1 human plexiform neurofibromas.
The data support testing of JAK/STAT inhibition and Wnt/ b-catenin
pathway inhibition in neurofibroma therapeutic trials. Supported by: NIH
R01 NS28840 to N.R. and NIH P50 NS057531 to N.R. and D.L.), a
DAMD New Investigator Award (W81XWH-11-1-0259) and an Ohio State
University Comprehensive Cancer Center Pelotonia Idea Grant (to J.W.).
The American Cancer Society (IRG-67-003-44) supported J.R.F.