IQUIBICEN   23947
INSTITUTO DE QUIMICA BIOLOGICA DE LA FACULTAD DE CIENCIAS EXACTAS Y NATURALES
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
"Protein malnutrition and premature aging: impact on cognitive skills and epigenetics mechanisms"
Autor/es:
EDUARDO T. CÁNEPA; NADINA M. FERRONI; SILVINA V. SONZOGNI
Lugar:
Alejandría
Reunión:
Workshop; IBRO-ARC Workshop on Epigenetic regulation of neurological functions: implications for pathology and therapeutics; 2018
Institución organizadora:
INTERNATIONAL BRAIN RESEARCH ORGANIZATION
Resumen:
Early‐life adversity increases the vulnerability to develop psychopathologies and cognitive decline later in life. Experiences of stress during this sensitive period, like malnutrition elicit long‐term effects on brain structure and function.Aging is an inevitable natural phenomenon mainly characterized by increased oxidative stress, elevated inflammatory response, accelerated cellular senescence and epigenetic changes. One important class of proteins governing the effects of aging is the sirtuin family. They are upregulated in aging and their function is the maintenance of genomic integrity against genotoxic agents, metabolites and oxidative stress. The aim of this work is to study if perinatal protein malnutrition (PM) predisposes the occurrence of premature aging in a murine model and the possible mechanisms. Mice dams were fed with a normal protein diet (NP, casein 20%) and a low protein diet (LP, casein 8%) during gestation and lactation. Offprings were evaluated at the ages of 2 month (young), 7 month (adult) and 12 month (old). We performed the Novel Place Recognition Test to evaluate spatial memory dependent of the hippocampus and we found than PM impaired this memory since they are young. Also, we performed a social olfactory test to study olfactory system functionality and discovered that LP mice lose this sense earlier than NP.The expression of sirtuin family was analyzed in the hippocampus. Sirt7 was upregulated by PM and aging while expression of Sirt1, Sirt2 and Sirt3 did not change. It is well known that Sirt7 is recruited to DNA double-strand breaks and it is widely expressed in brain regions affected during aging like hippocampus and olfactory areas. This might suggest an increased genome instability in the hippocampus of malnourished mice that could be related to impaired performance in cognitive tests. miR-26a is a senescence-associated microRNA which activates p16/pRb pathway and it downregulates brain-derived neurotrophic factor, a neurotrophin that plays an essential role in neuronal development and plasticity. We confirmed that miR-26a-5p expression increases with aging and we found a tendency in LP mice having higher levels in the hippocampus than NP. This might also contribute to the impaired spatial memory formation found in LP mice.