Spatial learning as activator of hippocampal neurogenesis during aging and development of Alzheimer\’s disease-like pathology

Poster (download) Alena Burnyasheva1, Tatiana Kozlova2, Ekaterina Rudnitskaya3, Natalia Stefanova41Institute of Cytology and Genetics SB RAS, burnyasheva@bionet.nsc.ru2Institute of Cytology and Genetics SB RAS, kozlova@bionet.nsc.ru3Institute of Cytology and Genetics SB RAS, rudnickaya@bionet.nsc.ru4Institute of Cytology and Genetics SB RAS, stefanovan@bionet.nsc.ru Adult neurogenesis in dentate gyrus (DG) is one of the key mechanisms of neuronal plasticity in hippocampus and plays an important role in cognitive function. However, the consequences of its alteration during healthy aging as well as development of neurodegeneration including Alzheimer’s disease (AD) remain unclear. It was shown that factors which can activate neurogenesis – such as physical exercises and learning – are able to improve cognitive function. Animal models are useful to clarify the connection between adult neurogenesis and cognitive function during development of AD signs, and OXYS rats are a suitable model for the most common sporadic form of AD. Here we examined effects of spatial learning on neurogenesis in DG of OXYS rats prior to and during manifestation of AD signs. We showed altered reference memory of OXYS rats already at the period prior to neurodegeneration. At the period of active manifestation of AD signs OXYS rats demonstrated altered spatial learning and reversal learning, whereas reference memory was altered only a little. At the period of active amyloid-ОІ accumulation in the brain only reference memory of OXYS rats was altered. Spatial learning resulted in accelerated maturation of immature cells of neuronal and astrocytic cell lineages in DG of OXYS and Wistar rats and decrease of amyloid-ОІ content in aged animals.

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MAPK pathways and alphaB-crystallin phosphorylation in brain: a focus on aging and Alzheimer’s disease

Poster (download) Natalia Muraleva11Institute of Cytology and Genetics SB RAS Novosibirsk, Russia, myraleva@bionet.nsc.ru Accumulation of intracellular damage and protein aggregates is an universal hallmark of aging and accompanies the development of some age-related diseases include Alzheimer’s disease (AD). Alpha-B-Crystallin (CryaB) as the molecular chaperone contributes maintenance of proteostasis by prevention of aggregation of proteins (e.g. amyloid beta) and enables their correct refolding. CryaB activity is regulated by MAPK signaling pathway (MAPKsp) through its phosphorylation. Nevertheless, the link between changes in MAPK-dependent CryaB phosphorylation with age and the development of AD remains unclear. Here, we examined p38 MAPK- and ERK-dependent phosphorylation of CryaB in the brain of Wistar rats with normal aging and senescence-accelerated OXYS rats at the different stages of the development of AD-like pathology, including the presymptomatic stage.  The most significant changes identified in the p38 MAPK-dependent CryaB phosphorylation. The level of p-Ser59-CryaB in the brain of Wistar rats increased with the age on the background of p38-MAPKsp activation. Similar but more significant changes accompanied the development of AD-like pathology in OXYS rats. The activation of ERK1/2-dependent CryaB phosphorylation (p-Ser45-CryaB) was detected at the early age and at the late stages of AD-like pathology in OXYS, while changes in the ERK1/2 signaling pathway were detected in Wistar rats with age. Thus, alteration of MAPK-dependent phosphorylation CryaB occurs with the normal aging. Manifestation and progression of the signs of the AD occurs against the background of activation of p38MAPK-dependent phosphorylation of CryaB. Activation of EPK-dependent CryaB phosphorylation is characteristic of the preclinical and progressive stage of the AD-like pathology.

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