Neuronal aging and memory loss. Contribution of lipid alterations and epigenetic factors.
Aging is associated with the loss of cognitive abilities. The vast majority of individuals show mild alterations such as memory loss associated with old age. In addition to this, aging provides an appropriate context for the development of more severe pathologies such as Alzheimer’s disease.
One of the characteristics of brain aging is that it is accompanied by changes in the lipid composition of neuronal membranes. In particular, in our laboratory we have described the loss of cholesterol and the accumulation of sphingolipids in old neurons of the hippocampus, a brain structure closely related to learning and memory processes.
The processes that occur in the cell membrane are strictly required for correct neuronal function, since memory formation begins with the activation of receptors on the plasma membrane. Furthermore, there is growing evidence that the signals transmitted between neurons induce changes in the chromatin structure, thus modulating the expression of genes involved in memory formation.
Using molecular and cell biology tools in cultures of hippocampal neurons and in aged mice, our laboratory is dedicated to analyzing the causes of changes in lipid composition that occur in old neurons, how these changes affect neuronal function, and how these lipid alterations lead to defects in the epigenetic mechanisms that regulate memory formation.
Lic. Qca. Leandro German Allende
CONICET doctoral fellow
Neuroscience PhD student, UNC.
FONCyT, CONICET, SECyT-UNC
PUBLICATIONS (LAST 5 YEARS)
Martin MG*, Ahmed T, Korovaichuk A, Venero C, Menchón S, Salas I, Munck S, Herreras O, Balschun D and Dotti CG*. 2014. Constitutive hippocampal cholesterol loss underlies poor cognition in old rodents. EMBO Mol Med. 6(7):902-17.
Martín MG*, Pfrieger F*, Dotti CG*. 2014. Cholesterol in brain disease: sometimes determinant and frequently implicated. EMBO Rep.15(10):1036-1052.
Palomer E, Carretero J, Benvegnú S, Dotti CG* and Martin MG*. 2016. Neuronal activity controls Bdnf expression via Polycomb de-repression and CREB/CBP/JMJD3 activation in mature neurons. Nature Communications. 7: 11081. DOI: 10.1038/ncomms11081.
Palomer E, Martín-Segura A, Baliyan S, Ahmed T, Balschun D, Venero C, Martin MG*, Dotti CG*. 2016. Aging Triggers a Repressive Chromatin State at Bdnf Promoters in Hippocampal Neurons. Cell Rep. Sep 13;16(11):2889-900.