Oligodendrocytes are multifunctional central nervous system (CNS) glia that are essential for neural function in gnathostomes. The evolutionary origins and specializations of the oligodendrocyte cell type are among the many remaining mysteries in glial biology and neuroscience. The role of oligodendrocytes as CNS myelinating glia is well established, but recent studies demonstrate that oligodendrocytes also participate in several myelin-independent aspects of CNS development, function, and maintenance. Furthermore, many recent studies have collectively advanced our understanding of myelin plasticity, and it is now clear that experience-dependent adaptations to myelination are an additional form of neural plasticity. These observations beg the questions of when and for which functions the ancestral oligodendrocyte cell type emerged, when primitive oligodendrocytes evolved new functionalities, and the genetic changes responsible for these evolutionary innovations. Here, I review recent findings and propose working models addressing the origins and evolution of the oligodendrocyte cell type and adaptive myelination. The core gene regulatory network (GRN) specifying the oligodendrocyte cell type is also reviewed as a means to probe the existence of oligodendrocytes in basal vertebrates and chordate invertebrates.
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Regional gray matter oligodendrocyte- and myelin-related measures are associated with differential susceptibility to stress-induced behavior in rats and humans
Individual reactions to traumatic stress vary dramatically, yet the biological basis of this variation remains poorly understood. Recent studies demonstrate the surprising plasticity of oligodendrocytes and myelin with stress and experience, providing a potential mechanism by which trauma induces aberrant structural and functional changes in the adult brain. In this study, we utilized a translational approach to test the hypothesis that gray matter oligodendrocytes contribute to traumatic-stress-induced behavioral variation in both rats and humans. We exposed adult, male rats to a single, severe stressor and used a multimodal approach to characterize avoidance, startle, and fear-learning behavior, as well as oligodendrocyte and myelin basic protein (MBP) content in multiple brain areas. We found that oligodendrocyte cell density and MBP were correlated with behavioral outcomes in a region-specific manner. Specifically, stress-induced avoidance positively correlated with hippocampal dentate gyrus oligodendrocytes and MBP. Viral overexpression of the oligodendrogenic factor Olig1 in the dentate gyrus was sufficient to induce an anxiety-like behavioral phenotype. In contrast, contextual fear learning positively correlated with MBP in the amygdala and spatial-processing regions of the hippocampus. In a group of trauma-exposed US veterans, T1-/T2-weighted magnetic resonance imaging estimates of hippocampal and amygdala myelin associated with symptom profiles in a region-specific manner that mirrored the findings in rats. These results demonstrate a species-independent relationship between region-specific, gray matter oligodendrocytes and differential behavioral phenotypes following traumatic stress exposure. This study suggests a novel mechanism for brain plasticity that underlies individual variance in sensitivity to traumatic stress.
more » « less- NSF-PAR ID:
- 10383264
- Publisher / Repository:
- Nature Publishing Group
- Date Published:
- Journal Name:
- Translational Psychiatry
- Volume:
- 11
- Issue:
- 1
- ISSN:
- 2158-3188
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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null (Ed.)Abstract The developing brain is marked by high plasticity, which can lead to vulnerability to early life stressors. Previous studies indicate that childhood maltreatment is associated with structural aberrations across a number of brain regions. However, prior work is limited by small sample sizes, heterogeneous age groups, the examination of one structure in isolation, the confounding of different types of early life stressors, and not accounting for socioeconomic status. These limitations may contribute to high variability across studies. The present study aimed to investigate how trauma is specifically associated with cortical thickness and gray matter volume (GMV) differences by leveraging a large sample of children ( N = 9270) from the Adolescent Brain Cognitive Development SM Study (ABCD Study ® ). A latent measure of trauma exposure was derived from DSM-5 traumatic events, and we related this measure of trauma to the brain using structural equation modeling. Trauma exposure was associated with thinner cortices in the bilateral superior frontal gyri and right caudal middle frontal gyrus ( p fdr - values < .001) as well as thicker cortices in the left isthmus cingulate and posterior cingulate ( p fdr - values ≤ .027), after controlling age, sex, and race/ethnicity. Furthermore, trauma exposure was associated with smaller GMV in the right amygdala and right putamen ( p fdr - values ≤ .048). Sensitivity analyses that controlled for income and parental education were largely consistent with the main findings for cortical thickness. These results suggest that trauma may be an important risk factor for structural aberrations, specifically for cortical thickness differences in frontal and cingulate regions in children.more » « less
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Scope Traumatic brain injury (TBI) compromises neuronal function required for hippocampal synaptic plasticity and cognitive function. Despite the high consumption of blueberries, information about its effects on brain plasticity and function under conditions of brain trauma is limited. The efficacy of dietary blueberry (BB) supplementation to mitigate the effects of TBI on plasticity markers and associated behavioral function in a rodent model of concussive injury are assessed.
Methods and results Rats were maintained on a diet supplemented with blueberry (BB, 5% w/w) for 2 weeks after TBI. It is found that BB supplementation mitigated a loss of spatial learning and memory performance after TBI, and reduced the effects of TBI on anxiety‐like behavior. BB supplementation prevents a reduction of molecules associated with the brain‐derived neurotrophic factor (BDNF) system action on learning and memory such as cyclic‐AMP response element binding factor (CREB), calcium/calmodulin‐dependent protein kinase II (CaMKII). In addition, BB supplementation reverses an increase of the lipid peroxidation byproduct 4‐hydroxy‐nonenal (4‐HNE) after TBI. Importantly, synaptic and neuronal signaling regulators change in proportion with the memory performance, suggesting an association between plasticity markers and behavior.
Conclusion Data herein indicate that BB supplementation has a beneficial effect in mitigating the acute aspects of the TBI pathology.
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Abstract A precise fear memory encoding a traumatic event enables an individual to avoid danger and identify safety. An impaired fear memory (contextual amnesia), however, puts the individual at risk of developing posttraumatic stress disorder (PTSD) due to the inability to identify a safe context when encountering trauma-associated cues later in life. Although it is gaining attention that contextual amnesia is a critical etiologic factor for PTSD, there is no treatment currently available that can reverse contextual amnesia, and whether such treatment can prevent the development of PTSD is unknown. Here, we report that (I) a single dose of transcranial photobiomodulation (PBM) applied immediately after tone fear conditioning can reverse contextual amnesia. PBM treatment preserved an appropriately high level of contextual fear memory in rats revisiting the “dangerous” context, while control rats displayed memory impairment. (II) A single dose of PBM applied after memory recall can reduce contextual fear during both contextual and cued memory testing. (III) In a model of complex PTSD with repeated trauma, rats given early PBM interventions efficiently discriminated safety from danger during cued memory testing and, importantly, these rats did not develop PTSD-like symptoms and comorbidities. (IV) Finally, we report that fear extinction was facilitated when PBM was applied in the early intervention window of memory consolidation. Our results demonstrate that PBM treatment applied immediately after a traumatic event or its memory recall can protect contextual fear memory and prevent the development of PTSD-like psychopathological fear in rats.
