Synaptic Pruning

Santos, Edalmarys; Noggle, Chad A.

doi:10.1007/978-0-387-79061-9_2856

Cited by 11 publications

(8 citation statements)

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“…After reaching the maximum density at 2 to 4 years of age, 9,10 in the following years synapses are physiologically eliminated in a process known as pruning. 11 Synapses that survive to adulthood are the ones stably maintained, although we have a certain degree of synapse formation and elimination throughout life. 12 Neuronal signal transmission in the CNS requires the presence of functional synapses, with properly arranged pre-and postsynaptic compartments.…”

Section: Introductionmentioning

confidence: 99%

Fluid Biomarkers for Synaptic Dysfunction and Loss

et al. 2020

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Synapses are the site for brain communication where information is transmitted between neurons and stored for memory formation. Synaptic degeneration is a global and early pathogenic event in neurodegenerative disorders with reduced levels of pre- and postsynaptic proteins being recognized as a core feature of Alzheimer’s disease (AD) pathophysiology. Together with AD, other neurodegenerative and neurodevelopmental disorders show altered synaptic homeostasis as an important pathogenic event, and due to that, they are commonly referred to as synaptopathies. The exact mechanisms of synapse dysfunction in the different diseases are not well understood and their study would help understanding the pathogenic role of synaptic degeneration, as well as differences and commonalities among them and highlight candidate synaptic biomarkers for specific disorders. The assessment of synaptic proteins in cerebrospinal fluid (CSF), which can reflect synaptic dysfunction in patients with cognitive disorders, is a keen area of interest. Substantial research efforts are now directed toward the investigation of CSF synaptic pathology to improve the diagnosis of neurodegenerative disorders at an early stage as well as to monitor clinical progression. In this review, we will first summarize the pathological events that lead to synapse loss and then discuss the available data on established (eg, neurogranin, SNAP-25, synaptotagmin-1, GAP-43, and α-syn) and emerging (eg, synaptic vesicle glycoprotein 2A and neuronal pentraxins) CSF biomarkers for synapse dysfunction, while highlighting possible utilities, disease specificity, and technical challenges for their detection.

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Section: Introductionmentioning

confidence: 99%

Fluid Biomarkers for Synaptic Dysfunction and Loss

et al. 2020

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“…These physiological processes include myelinogenesis [22,42,46], synaptic pruning and dendritic arborisation [26,42,46,47], which lead to reduction in the size and number of neurons and their synaptic processes [26,42,46]. These neurodevelopmental processes work together to reinforce and strengthen fibres and connections that are used consistently for transmitting brain impulses, while redundant fibres are "pruned" or removed [48]. The process of myelination in the lower cortical layer closest to the cortical white/grey matter interface may be the main process that influences cortical thinning with brain growth [22,42,49].…”

Section: Morphometric Development In Typically-developing Hiv-childre...mentioning

confidence: 99%

Similar cortical morphometry trajectories from 5 to 9 years in children with perinatal HIV who started treatment before age 2 years and uninfected controls

et al. 2023

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Background Life-long early ART (started before age 2 years), often with periods of treatment interruption, is now the standard of care in pediatric HIV infection. Although cross-sectional studies have investigated HIV-related differences in cortical morphology in the setting of early ART and ART interruption, the long-term impact on cortical developmental trajectories is unclear. This study compares the longitudinal trajectories of cortical thickness and folding (gyrification) from age 5 to 9 years in a subset of children perinatally infected with HIV (CPHIV) from the Children with HIV Early antiRetroviral therapy (CHER) trial to age-matched children without HIV infection. Methods 75 CHER participants in follow-up care at FAMCRU (Family Centre for Research with Ubuntu), as well as 66 age-matched controls, received magnetic resonance imaging (MRI) on a 3 T Siemens Allegra at ages 5, 7 and/or 9 years. MR images were processed, and cortical surfaces reconstructed using the FreeSurfer longitudinal processing stream. Vertex-wise linear mixed effects (LME) analyses were performed across the whole brain to compare the means and linear rates of change of cortical thickness and gyrification from 5 to 9 years between CPHIV and controls, as well as to examine effects of ART interruption. Results Children without HIV demonstrated generalized cortical thinning from 5 to 9 years, with the rate of thinning varying by region, as well as regional age-related gyrification increases. Overall, the means and developmental trajectories of cortical thickness and gyrification were similar in CPHIV. However, at an uncorrected p < 0.005, 6 regions were identified where the cortex of CPHIV was thicker than in uninfected children, namely bilateral insula, left supramarginal, lateral orbitofrontal and superior temporal, and right medial superior frontal regions. Planned ART interruption did not affect development of cortical morphometry. Conclusions Although our results suggest that normal development of cortical morphometry between the ages of 5 and 9 years is preserved in CPHIV who started ART early, these findings require further confirmation with longitudinal follow-up through the vulnerable adolescent period.

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“…Microglia-derived cytokines, such as TNF-α, have been reported to regulate the pruning of neuronal synapses (229,230). Efficient synaptic pruning is most active from the age of two and is vital for brain plasticity, which is thought to be lacking in ASD (231,232). Researchers have found an increase in synapse number and evidence of under-pruning when examining the brains of children with ASD (233).…”

Section: Glia In Autism Spectrum Disordermentioning

confidence: 99%

Neuronal Cell Adhesion Molecules May Mediate Neuroinflammation in Autism Spectrum Disorder

et al. 2022

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Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by restrictive and repetitive behaviors, alongside deficits in social interaction and communication. The etiology of ASD is largely unknown but is strongly linked to genetic variants in neuronal cell adhesion molecules (CAMs), cell-surface proteins that have important roles in neurodevelopment. A combination of environmental and genetic factors are believed to contribute to ASD pathogenesis. Inflammation in ASD has been identified as one of these factors, demonstrated through the presence of proinflammatory cytokines, maternal immune activation, and activation of glial cells in ASD brains. Glial cells are the main source of cytokines within the brain and, therefore, their activity is vital in mediating inflammation in the central nervous system. However, it is unclear whether the aforementioned neuronal CAMs are involved in modulating neuroimmune signaling or glial behavior. This review aims to address the largely unexplored role that neuronal CAMs may play in mediating inflammatory cascades that underpin neuroinflammation in ASD, primarily focusing on the Notch, nuclear factor-κB (NF-κB), and mitogen-activated protein kinase (MAPK) cascades. We will also evaluate the available evidence on how neuronal CAMs may influence glial activity associated with inflammation. This is important when considering the impact of environmental factors and inflammatory responses on ASD development. In particular, neural CAM1 (NCAM1) can regulate NF-κB transcription in neurons, directly altering proinflammatory signaling. Additionally, NCAM1 and contactin-1 appear to mediate astrocyte and oligodendrocyte precursor proliferation which can alter the neuroimmune response. Importantly, although this review highlights the limited information available, there is evidence of a neuronal CAM regulatory role in inflammatory signaling. This warrants further investigation into the role other neuronal CAM family members may have in mediating inflammatory cascades and would advance our understanding of how neuroinflammation can contribute to ASD pathology.

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Synaptic Pruning

Cited by 11 publications

References 1 publication

Fluid Biomarkers for Synaptic Dysfunction and Loss

Fluid Biomarkers for Synaptic Dysfunction and Loss

Similar cortical morphometry trajectories from 5 to 9 years in children with perinatal HIV who started treatment before age 2 years and uninfected controls

Neuronal Cell Adhesion Molecules May Mediate Neuroinflammation in Autism Spectrum Disorder

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