Age-Dependent Decline of Nogo-A Protein in the Mouse Cerebrum

Abstract

Nogo-A, a myelin-associated neurite growth inhibitory protein, is implicated in synaptic plasticity. It binds to its receptor namely the Nogo-66 receptor1 (NgR1) and regulates filamentous (F) actin dynamics via small GTPases of the Rho family, RhoA kinase (ROCK), LimK and cofilin. These proteins are associated with the structural plasticity, one of the components of synaptic plasticity, which is known to decline with normal aging. So, the level of Nogo-A and its receptor NgR1 are likely to vary during normal brain aging. However, it is not clearly understood how the levels of Nogo-A and its receptor NgR1 change in the cerebrum during aging. Several studies show an age- and gender-dependent decline in synaptic plasticity. Therefore, the present study was planned to analyze the relative changes in the mRNA and protein levels of Nogo-A and NgR1 in both male and female mice cerebrum during normal aging. Western blot analysis has shown decrease in Nogo-A protein level during aging in both male and female mice cerebrum. This was further confirmed by immunofluorescence analysis. RT-PCR analysis of Nogo-A mRNA showed no significant difference in the above-mentioned groups. This was also supported by in situ hybridization. NgR1 protein and its mRNA expression levels showed no significant alteration with aging in the cerebrum of both male and female mice. Taken together, we speculate that the downregulation of Nogo-A protein might have a role in the altered synaptic plasticity during aging.

Male brain ages faster: the age and gender dependence of subcortical volumes

“…However, findings of post-mortem histological studies suggested, that it is rather the size than the number of the individual cells explaining the age-related decline of GM (Terry et al 1987;Peters et al 1998). At the molecular level the expression of NoGo-A, a myelin-associated neurite growth inhibitor protein decreases with age (Kumari and Thakur 2014). Recent results also imply the impact of aging on GM/ WM diffusion changes, explaining some cognitive variability and even decline (Salminen et al 2015).…”

Age-associated Cognitive Decline: Insights into Molecular Switches and Recovery Avenues

“…Nogo-A is a myelin-associated neurite growth inhibitory protein, that binds to its receptor Nogo-66 receptor1 (NgR1) and regulates filamentous actin dynamics and involved in structural plasticity of the synapses. We demonstrated that Nogo-A protein level decreased in male and female forebrain of old mice while NgR1 remained unaltered [ 42 ]. In recent years, another set of synaptic proteins neurexins (Nrxns) and neuroligins (Nlgns) have emerged as potential candidates for alterations in structural synaptic plasticity.…”

The Influence of Neuron-Extrinsic Factors and Aging on Injury Progression and Axonal Repair in the Central Nervous System

“…Few studies examined how age alters the expression of these proteins. Nogo-A levels are significantly decreased in aged animals (Trifunovski et al, 2006;Kumari and Thakur, 2014). A decrease in recovery is surprisingly observed in 12-month-old Nogo A/B deficient mice after TBI, compared to young adults, possibly related to hypomyelination (Marklund et al, 2009).…”