The Canadian Open Neuroscience Platform-An open science framework for the neuroscience community.

The Canadian Open Neuroscience Platform (CONP) takes a multifaceted approach to enabling open neuroscience, aiming to make research, data, and tools accessible to everyone, with the ultimate objective of accelerating discovery. Its core infrastructure is the CONP Portal, a repository with a decentralized design, where datasets and analysis tools across disparate platforms can be browsed, searched, accessed, and shared in accordance with FAIR principles. Another key piece of CONP infrastructure is NeuroLibre, a preprint server capable of creating and hosting executable and fully reproducible scientific publications that embed text, figures, and code. As part of its holistic approach, the CONP has also constructed frameworks and guidance for ethics and data governance, provided support and developed resources to help train the next generation of neuroscientists, and has fostered and grown an engaged community through outreach and communications. In this manuscript, we provide a high-level overview of this multipronged platform and its vision of lowering the barriers to the practice of open neuroscience and yielding the associated benefits for both individual researchers and the wider community.

HDAC inhibition leads to age-dependent opposite regenerative effect upon PTEN deletion in rubrospinal axons after SCI.

Epigenetic changes associated with aging have been linked to functional and cognitive deficits in the adult CNS. Histone acetylation is involved in the control of the transcription of plasticity and regeneration-associated genes. The intrinsic axon growth capacity in the CNS is negatively regulated by phosphatase and tensin homolog (Pten). Inhibition of Pten is an effective method to stimulate axon growth following an injury to the optic nerve, corticospinal tract (CST), and rubrospinal tract (RST). Our laboratory has previously demonstrated that the deletion of Pten in aged animals diminishes the regenerative capacity in rubrospinal neurons. We hypothesize that changes in the chromatin structure might contribute to this age-associated decline. Here, we assessed whether Trichostatin A (TSA), a histone deacetylases (HDACs) inhibitor, reverses the decline in regeneration in aged Ptenf/f mice. We demonstrate that HDAC inhibition induces changes in the expression of GAP43 in both young and aged Ptenf/f mice. The regenerative capacity of the RST did not improve significantly in young mice, neither their motor function on the horizontal ladder or cylinder test after TSA treatment for 7 days. Interestingly, TSA treatment in the aged mice worsened their motor function deficits, suggesting that the systemic treatment with TSA might have an overall adverse effect on motor recovery after SCI in aged animals.

Power to the People: Addressing Big Data Challenges in Neuroscience by Creating a New Cadre of Citizen Neuroscientists.

Global neuroscience projects are producing big data at an unprecedented rate that informatic and artificial intelligence (AI) analytics simply cannot handle. Online games, like Foldit, Eterna, and Eyewire-and now a new neuroscience game, Mozak-are fueling a people-powered research science (PPRS) revolution, creating a global community of "new experts" that over time synergize with computational efforts to accelerate scientific progress, empowering us to use our collective cerebral talents to drive our understanding of our brain.

SPARC expression by cerebral microvascular endothelial cells in vitro and its influence on blood-brain barrier properties.

BACKGROUND: SPARC (secreted protein acidic and rich in cysteine) is a nonstructural, cell-matrix modulating protein involved in angiogenesis and endothelial barrier function, yet its potential role in cerebrovascular development, inflammation, and repair in the central nervous system (CNS) remains undetermined. METHODS: This study examines SPARC expression in cultured human cerebral microvascular endothelial cells (hCMEC/D3)-an in vitro model of the blood-brain barrier (BBB)-as they transition between proliferative and barrier phenotypes and encounter pro-inflammatory stimuli. SPARC protein levels were quantified by Western blotting and immunocytochemistry and messenger RNA (mRNA) by RT-PCR. RESULTS: Constitutive SPARC expression by proliferating hCMEC/D3s is reduced as cells mature and establish a confluent monolayer. SPARC expression positively correlated with the proliferation marker Ki-67 suggesting a role for SPARC in cerebrovascular development. The pro-inflammatory molecules tumor necrosis factor-α (TNF-α) and endotoxin lipopolysaccharide (LPS) increased SPARC expression in cerebral endothelia. Interferon gamma (IFN-γ) abrogated SPARC induction observed with TNF-α alone. Barrier function assays show recombinant human (rh)-SPARC increased paracellular permeability and decreased transendothelial electrical resistance (TEER). This was paralleled by reduced zonula occludens-1 (ZO-1) and occludin expression in hCMEC/D3s exposed to rh-SPARC (1-10 µg/ml) compared with cells in media containing a physiological dose of SPARC. CONCLUSIONS: Together, these findings define a role for SPARC in influencing cerebral microvascular properties and function during development and inflammation at the BBB such that it may mediate processes of CNS inflammation and repair.

BigNeuron: Large-Scale 3D Neuron Reconstruction from Optical Microscopy Images.

Understanding the structure of single neurons is critical for understanding how they function within neural circuits. BigNeuron is a new community effort that combines modern bioimaging informatics, recent leaps in labeling and microscopy, and the widely recognized need for openness and standardization to provide a community resource for automated reconstruction of dendritic and axonal morphology of single neurons.

Epigenetics DNA methylation in the core ataxin-2 gene promoter: novel physiological and pathological implications.

Pathogenic CAG (cytosine-adenine-guanine) expansions beyond certain thresholds in the ataxin-2 (ATXN2) gene cause spinocerebellar ataxia type 2 (SCA2) and were shown to contribute to Parkinson disease, amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Regulation of ATXN2 gene expression and the function of the protein product are not known. SCA2 exhibits an inverse correlation between the size of the CAG repeat and the age at disease onset. However, a wide range of age at onset are typically observed, with CAG repeat number alone explaining only partly this variability. In this study, we explored the hypothesis that ATXN2 levels could be controlled by DNA methylation and that the derangement of this control may lead to escalation of disease severity and influencing the age at onset. We found that CpG methylation in human ATXN2 gene promoter is associated with pathogenic CAG expansions in SCA2 patients. Different levels of methylation in a SCA2 pedigree without an intergenerational CAG repeat instability caused the disease anticipation in a SCA2 family. DNA methylation also influenced the disease onset in SCA2 homozygotes and SCA3 patients. In conclusion, our study points to a novel regulatory mechanism of ATXN2 expression involving an epigenetic event resulting in differential disease course in SCA2 patients.

A re-assessment of the consequences of delayed transplantation of olfactory lamina propria following complete spinal cord transection in rats.

This study is part of the NIH "Facilities of Research-Spinal Cord Injury" contract to support independent replication of published studies. We repeated a study reporting that delayed transplantation of olfactory lamina propria (OLP) into the site of a complete spinal cord transection led to significant improvement in hindlimb motor function and induced axon regeneration. Adult female rats received complete spinal cord transections at T10. Thirty days post-injury, pieces of OLP, which contains olfactory ensheathing cells (OECs), or respiratory lamina propria (RLP), which should not contain OECs, were placed into the transection site. Hindlimb motor function was tested using the BBB scale from day 1 post-injury through 10 weeks following transplantation. To assess axonal regeneration across the transection site, Fluorogold was injected into the distal segment, and the distribution of 5HT-containing axons was assessed using immunostaining. BBB analyses revealed no significant recovery after OLP transplantation and no significant differences between OLP vs. RLP transplant groups. Fluorogold injections into caudal segments did not lead to retrograde labeling in any animals. Immunostaining for 5HT revealed that a few 5HT-labeled axons extended into both RLP and OLP transplants and a few 5HT-labeled axons were present in sections caudal to the injury in 2 animals that received OLP transplants and 1 animal that received RLP transplants. Our results indicate that, although OLP transplants may stimulate regeneration under some circumstances, the effect is not so robust as to reliably overcome the hostile setting created by a complete transection paradigm.