Impairment of cognitive features including hippocampus-dependent spatial learning and memory affects nearly half of the aged population. performance in individual rats. Immunohistochemical experiments exhibited that upregulation of MAIs occurs in part in hippocampal neuronal axons and somata. While a number of pathways and processes are altered with brain aging we report a coordinated induction of myelin-associated inhibitors of functional and structural plasticity only in cognitively impaired aged rats. Induction of MAIs may decrease stimulus-induced synaptic strengthening and structural remodeling ultimately impairing synaptic mechanisms of spatial learning and memory and resulting in cognitive decline. 2009 Avasimibe (CI-1011) 2010 2005 As the quality and availability of health care in developed countries continue to improve the aged population is expected to continue to increase (Social Science Data Analysis Network 2010;Shrestha 2006). The prevalence of age-related cognitive decline is usually expected to rise Aviptadil Acetate concomitantly with the increase in our lifespan. As such greater emphasis must be placed on understanding preventing and treating cognitive impairment. The neurobiological basis of n o nneurodegenerative cognitive decline which occurs in the absence of neuronal cell death or neuropathology (Rapp and Gallagher 1996;Rapp 2002;Rasmussen 1996) remains to be determined but most likely involves impaired hippocampal synaptic signaling and regulation [reviewed in (Hof and Morrison 2004)]. Impaired hippocampal function connected with maturing is apparent in human beings (Schaie 1996) monkeys (Rapp and Amaral 1989) rats (Rapp and Gallagher 1996) and mice (Gower and Lamberty 1993). Modifications in neurobiologically-relevant procedures including decreased appearance of synaptic equipment increased oxidative stress decreased glucose metabolism and aberrant protein folding and trafficking are characteristic of the aging hippocampus [reviewed in (VanGuilder and Freeman 2011)]. Although these processes are important to healthy brain function dysregulation of neurotransmission and synaptic plasticity is likely a more immediate cause of cognitive impairment. Avasimibe (CI-1011) Electrophysiological studies of hippocampal function demonstrate signaling disruptions with aging and spatial learning and memory impairment and are consistent with unstable encoding of spatial information. This instability manifests in decreased long-term potentiation increased long-term depressive disorder and errors in activation of spatiotemporal ensemble network sequences (Barnes 1997;Kumar 2007;Norris 1996;Rosenzweig and Barnes 2003). These electrophysiological characteristics are associated with impaired neurotransmitter synthesis and receptor signaling dysregulated neuronal gene and protein expression and atypical synapse morphology (Burke and Barnes 2006;Liu 2008;Poe 2001;Shi 2005). We have previously reported the age-related downregulation of neurotransmission-associated proteins with functions in synaptic vesicle mobilization release and reuptake in agreement with deficits of neurotransmission characteristic of hippocampal aging (VanGuilder 2010). Additionally we have described decreased expression of proteins that mediate activity-dependent plasticity [14-3-3 theta (Skoulakis and Davis 1998) CamK2α (Lu and Hawkins 2006) and PSD-95 (Vickers 2006)] and increased expression of modulators/stabilizers of neuronal and synaptic structure [MAP2 (Harada 2002) drebrin (Majoul 2007) Avasimibe (CI-1011) Avasimibe (CI-1011) Nogo-A (Zagrebelsky 2010)] in hippocampal synaptosomes derived aged cognitively impaired rats compared to aged cognitively intact and adult rats (VanGuilder 2011b). Together with exhibited deficits of electrophysiological correlates of learning and memory in cognitively impaired rodents these data further implicate age-associated dysregulation of synaptic plasticity in cognitively impaired subjects as a potential basis of hippocampal dysfunction and impaired spatial learning and memory. In recent years the myelin-associated inhibitors (MAIs) myelin-associated glycoprotein (MAG) Nogo-A (neurite outgrowth inhibitor A) and oligodendrocyte myelin glycoprotein (OMgp) have emerged as potent inhibitors of neuronal outgrowth and structural plasticity (Akbik 2011;Cafferty and Strittmatter 2006;Cafferty 2010;Llorens 2011). By signaling through one of their common receptors NgR1 (Nogo-66 receptor 1) MAIs Avasimibe (CI-1011) stabilize synaptic ultrastructure by modulating cytoskeletal rearrangements (Lee 2008;Zagrebelsky 2010) and suppress activity- and experience-dependent synaptic plasticity (Delekate 2011;Raiker 2010). These actions are similar to.