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Macro-connectomics and microstructure predict dynamic plasticity patterns in the non-human primate brain.

ABSTRACT: The brain displays a remarkable ability to adapt following injury by altering its connections through neural plasticity. Many of the biological mechanisms that underlie plasticity are known, but there is little knowledge as to when, or where in the brain plasticity will occur following injury. This knowledge could guide plasticity-promoting interventions and create a more accurate roadmap of the recovery process following injury. We causally investigated the time-course of plasticity after hippocampal lesions using multi-modal MRI in monkeys. We show that post-injury plasticity is highly dynamic, but also largely predictable on the basis of the functional connectivity of the lesioned region, gradients of cell densities across the cortex and the pre-lesion network structure of the brain. The ability to predict which brain areas will plastically adapt their functional connectivity following injury may allow us to decipher why some brain lesions lead to permanent loss of cognitive function, while others do not.

SUBMITTER: Froudist-Walsh S

PROVIDER: S-EPMC6249000 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Macro-connectomics and microstructure predict dynamic plasticity patterns in the non-human primate brain.

Froudist-Walsh Sean S Browning Philip Gf PG Young James J JJ Murphy Kathy L KL Mars Rogier B RB Fleysher Lazar L Croxson Paula L PL

eLife 20181121

The brain displays a remarkable ability to adapt following injury by altering its connections through neural plasticity. Many of the biological mechanisms that underlie plasticity are known, but there is little knowledge as to when, or where in the brain plasticity will occur following injury. This knowledge could guide plasticity-promoting interventions and create a more accurate roadmap of the recovery process following injury. We causally investigated the time-course of plasticity after hippo ...[more]

PMID: 30462609

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Project description:MicroRNAs (miRNAs) are small noncoding RNAs that negatively regulate gene expression post-transcriptionally. They play a critical role in developmental and physiological processes and have been implicated in the pathogenesis of several diseases including cancer. To identify miRNA signatures associated with different stages of neoplastic development, we examined the expression profile of 776 primate miRNAs in the following cells: primary African green monkey kidney (pAGMK) cells; spontaneously immortalized, non-tumorigenic, low-passage VERO cells (10-87 LP); tumorigenic, high-passage VERO cells (10-87 HP); and a cell line (10-87 T) derived from a 10-87 HP cell tumor xenograft in athymic nude mice. When compared with pAGMK cells, the majority of miRNAs were expressed at lower levels in 10-87 LP, 10-87 HP, and 10-87 T cells. We identified 10 up-regulated miRNAs whose level of expression correlated with VERO cell evolution from a non-tumorigenic phenotype to a tumorigenic phenotype. Several miRNAs that were components of the tumorigenic phenotype-specific signatures in our AGMK model are also found in a variety of human tumors. This may prove to be of general relevance to the biology of neoplastic development as it occurs both in vivo as well as in vitro. In addition, one or more of these miRNAs could be potential biomarkers for the expression of the tumorigenic phenotype of VERO cells. The spontaneousely transformed VERO cells, non-tumorigenic, were pasasged at low density in culture up to 250. The high passage (p250) was found to be tumorigenic. The cell line from xenograft of high passage was also established. We then evaluated patterns of miRNA expression in pAGMK cells and in derivatives of the 10-87 VERO cell line (10-87 LP cells, 10-87 HP cells, and 10-87 T cells) in an attempt to identify the miRNAs whose altered expression might correlate with, and perhaps be involved in, the evolution of the neoplastic phenotypes that occurred during passage of these AGMK cells in tissue culture. performed high-throughput miRNA profiling to audit the expression level of miRNAs in pAGMK cells and in VERO cells at non-tumorigenic and tumorigenic stages of neoplastic development. The analysis involved pAGMK cells, non-tumorigenic 10-87 low-passage VERO cells (10-87 LP) tumorigenic, high-passage VERO cells (10-87 HP) and a cell line (10-87 T) derived from a 10-87 HP cell tumor xenograft in athymic nude mice.

Dataset Information

Macro-connectomics and microstructure predict dynamic plasticity patterns in the non-human primate brain.

Publications

Macro-connectomics and microstructure predict dynamic plasticity patterns in the non-human primate brain.

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