Researchers at the Montreal Neurological Institute and Hospital - The Neuro at McGill University, have compiled a new detailed map of the hippocampal region of the brain. This new submillimetric data set has been designed to help the scientific community to develop better treatments for patients suffering from epilepsy and other psychiatric and neurological disorders. Research has been set out to build and share a detailed model of the substructures, the hippocampus, the keycentre of the brain involved in epilepsy. The goal of this project is to improve the tools available for clinicians and researchers of the neurological field around the globe and accelerate research.
Neuronal BRCA1 levels are regulated by neuronal activity. Neuronal reductions in BRCA1 cause increased persistence of DSBs, abnormal chromatin remodeling, cellular dysfunction and cognitive deficits. Knockdown of BRCA1 does not cause neuronal apoptosis but causes abnormal chromatin remodeling in vitro and in vivo, reduces neuronal size, increases neuronal excitability and impairs LTP. BRCA1 depletion alters neuronal structure and function. BRCA1 reduction causes learning and memory deficits in mice.
In exploring the mechanisms that may underlie these abnormalities, scientists discovered that the size of cell bodies and dendritic arbours was reduced in neurons expressing low levels of BRCA1. Changes in dendritic complexity, including length and branching, also occur in AD patients, AD-related animal models and other neurodegenerative diseases. Physiological neuronal activation increased BRCA1 levels, whereas stimulating predominantly extrasynaptic N-methyl-D-aspartate receptors promoted the proteasomal degradation of BRCA1.
The conclusion is that BRCA1 is regulated by neuronal activity, protects the neuronal genome, and critically supports neuronal integrity and cognitive functions. Pathological accumulation of Aβ depletes neuronal BRCA1, which may contribute to cognitive deficits in AD.