Neuroscience PerspectiveAcetylcholinesterase Inhibitors May Improve Myelin Integrity
Section snippets
The Myelin Model of the Human Brain
The four types of data outlined above are interpreted in the context of a myelin-centered model of human brain development and degeneration (Bartzokis 2004a, Bartzokis 2004b, Bartzokis 2005) that will briefly be summarized here. The human brain is unique, even among primates (Schoenemann et al. 2005), in its extensive and pervasive myelination process that supports its high-capacity information processing (Bartzokis 2004a). The lifelong trajectory of brain myelination has a quadratic-like
The Cholinergic System and the Continual Process of Myelination and Repair
The complex cholinergic (nicotinic and muscarinic) receptor changes in brain development, aging, and associated disease states (Court et al 1997, Pimlott et al 2004, Sihver et al 1998) support the possibility that nonneuronal cholinergic targets may contribute to efficacy of cholinergic treatments. A large proportion (up to 90%) of cholinergic transmission both in the developing and adult brain is nonsynaptic, with acetylcholine being released from cholinergic varicosities into the
Nonsynaptic Effects of Cholinergic Treatments may Explain Their Wide Spectrum of Efficacy
Recent clinical trials have revealed a very wide spectrum of efficacy of cholinergic treatments that span developmental and degenerative disorders as well as the “normal” myelin breakdown process leading to dementia. AChEIs can improve cognition in patients with MCI (Salloway et al. 2004). Moreover, such treatment delayed the progression from MCI to AD especially in patients that carried the ApoE4 allele (Petersen et al. 2005), and the ApoE4 allele is known to lower the age at onset of AD (
Conclusions
It is proposed that at least part of the efficacy demonstrated by cholinergic treatments of neuropsychiatric diseases may be attributed to nonsynaptic effects on oligodendrocytes and myelin. Many details remain to be investigated in order to fully understand the role of nonsynaptic cholinergic effects on brain development-to-degeneration myelination trajectories. The hypotheses presented above are testable through in vivo imaging technologies that provide new avenues of assessing the trajectory
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Substance abuse and white matter: Findings, limitations, and future of diffusion tensor imaging research
2019, Drug and Alcohol DependenceButyrylcholinesterase genotype and gender influence Alzheimer's disease phenotype
2013, Alzheimer's and DementiaCitation Excerpt :Hypoactive or dystrophic microglia and low levels of apoE may underlie the synaptic failure, neuronal tau aggregation, and accumulation of Aβ characteristic of the early synaptic failure phenotype. These focal areas of cortical pathology are also in the later-myelinating regions, such as the temporal and frontal lobes, which hint at potential commonality between upstream pathophysiologic mechanisms underlying both phenotypes [26]. Indeed, the difference between the two phenotypes may be that chronic exposure to higher levels of Aβ aggregates in ɛ4- and K-carriers before the symptomatic stage suggests—in areas of the brain such as the default mode network with high Aβ production—that glia have become senescent and nonfunctional.
Brain axial and radial diffusivity changes with age and gender in healthy adults
2013, Brain ResearchNeuroglialpharmacology: Myelination as a shared mechanism of action of psychotropic treatments
2012, NeuropharmacologyCitation Excerpt :In addition to acetylcholine, catecholamines (primarily dopamine, serotonin, and norepinephrine) are also largely (>50–80%) non-synaptically released (Descarries et al., 1996; Parent et al., 2010; Smiley et al., 1994; Umbriaco et al., 1995) (reviewed in Fuxe and Agnati, 1991). These non-synaptic and extra-synaptic neuroglial communications can impact oligodendrocyte differentiation and myelination (reviewed in Bartzokis, 2007, 2011b). It is of interest to note that glia may also influence neurotransmitter-based extra- and non-synaptic signaling through secretion of most of the extracellular matrix components such as reelin (see Section 5.2.1) and chondroitin sulfate proteoglycans.