New Article with drawings: Wnt-5a increases NO and modulates NMDA receptor in rat hippocampal neurons

Wnt-5a increases NO and modulates NMDA receptor in rat hippocampal neurons

Francisco J. Muñoz^a, b, 

Juan A. Godoy^a, 

Waldo Cerpa^c, 

Inés M. Poblete^a, d, 

Juan Pablo Huidobro-Toro^a,d, 

Nibaldo C. Inestrosa^a, e

Abstract

Wnt signaling has a crucial role in synaptic function at the central nervous system. Here we evaluate whetherWnts affect nitric oxide (NO) generation in hippocampal neurons. We found that non-canonical Wnt-5atriggers NO production; however, Wnt-3a a canonical ligand did not exert the same effect. Co-administration of Wnt-5a with the soluble Frizzled related protein-2 (sFRP-2) a Wnt antagonist blocked the NO production.Wnt-5a activates the non-canonical Wnt/Ca²⁺ signaling through a mechanism that depends on Ca²⁺ release from Ryanodine-sensitive internal stores. The increase in NO levels evoked by Wnt-5a promotes the insertion of the GluN2B subunit of the NMDA receptor (NMDAR) into the neuronal cell surface. To the best of our knowledge, this is the first time that Wnt-5a signaling is related to NO production, which in turn increases NMDARs trafficking to the cell surface.

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New research Article with drawings: SIRT1 Protects Dendrites, Mitochondria and Synapses from Aβ Oligomers in Hippocampal Neurons

SIRT1 Protects Dendrites, Mitochondria and Synapses from Aβ Oligomers in Hippocampal Neurons

Juan A Godoy¹, ¹Centro de Envejecimiento y Regeneración (CARE); Departamento de Biología Celular, Molecular; Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, ChileClaudio Allard¹, ¹Centro de Envejecimiento y Regeneración (CARE); Departamento de Biología Celular, Molecular; Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, ChileMacarena S Arrázola¹, ²Departamento de Biología, Facultad de Ciencias, Universidad de Tarapacá, Arica, ChileJuan M Zolezzi² and ¹Centro de Envejecimiento y Regeneración (CARE); Departamento de Biología Celular, Molecular; Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, ChileNibaldo C Inestrosa^1*

Aging is a major risk factor in the onset of neurodegenerative diseases, such as Alzheimer’s disease (AD). SIRT1, a β-NAD+-dependent histone deacetylase activity, holds great potential for promoting longevity, preventing against disease and increasing cell survival. We report here, that SIRT1 protects against the damage caused by Aβ oligomers at the level of synaptic contacts, dendritic branching and mitochondrial structure in cultured rat hippocampal neurons. Neurons overexpressing SIRT1 showed increased synaptic contacts, dendritic branching and preserved mitochondrial morphology, suggesting the prevention of the Aβ oligomer-mediated neurodegeneration. Such effects were not observed in neurons overexpressing a dominant negative form of SIRT1. The potential underlying signaling pathways involved in the SIRT1 neuroprotective mechanism are discussed in the context of the peroxisome proliferator-activated receptors (PPARs), peroxisome proliferator activated receptor co-activator 1α (PGC-1α), mTOR, and the Wnt signaling pathway. Our results suggest that SIRT1 modulation might well be a therapeutic agent to protect against neurodegenerative diseases, like AD.