Velizhanina, M. | Search bioRxiv

bioRxiv2026

Does transection severity determine the way of spinal cord repair in the spiny mouse?

The mechanisms of the spinal cord regeneration after complete spinal cord transection were investigated in spiny mice. In some animals, the appearance of quadrupedal overground stepping together with rewiring of the direct propriospinal projections between the cervical and lumbar enlargements was revealed. In others, no stepping recovery was detected, whereas numerous cells labeled by the neuronal proteins NeuN and {beta}III-tubulin were observed within the injury region. We suggest that depending on trauma severity, different repair mechanisms are elicited: only connectome restoration or both connectome restoration and the activation of neurogenesis. To confirm the high neurogenic potential of spiny mice, a primary culture of bone marrow was established. Unlike in other mammals, bone marrow pluripotent cells in the culture differentiated into neuronal cells without any chemical stimulation. These findings provide strong evidence for the high differentiation potential of spiny mouse stem cells toward neural lineages. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=180 SRC="FIGDIR/small/739224v1_ufig1.gif" ALT="Figure 1"> View larger version (73K): org.highwire.dtl.DTLVardef@1e6f2c1org.highwire.dtl.DTLVardef@14b88f6org.highwire.dtl.DTLVardef@ce5b5org.highwire.dtl.DTLVardef@bcebd9_HPS_FORMAT_FIGEXP M_FIG C_FIG HIGHLIGHTSO_LITwo regenerative mechanisms are proposed in spiny mice, depending on the severity the spinal cord transection C_LIO_LIRegular transection evoked the emergence of the direct propriospinal projections C_LIO_LISevere transection evoked the neurogenesis within the primary injured region C_LIO_LIPrimary culture of bone marrow cells from spiny mice exhibits neurogenic differentiation without chemical induction C_LI

neuroscience↗

bioRxiv2019

Amyloid conformers of the FXR1 protein prevent mRNA degradation in cortical neurons

Functional amyloids regulate vital processes in a variety of organisms from bacteria to higher eukaryotes. The development of methods enabling large-scale screening for amyloids opens up opportunity for systemic analysis of the prevalence of amyloids in nature. Using an original proteomic approach, we identified several proteins forming amyloid-like detergent-resistant aggregates in the rat brain. One of them is the FXR1 protein, which is known to regulate memory and emotions (1, 2). We demonstrated that in brain FXR1 forms amyloid oligomers and insoluble detergent-resistant aggregates that strongly colocalize with amyloid-specific dye Thioflavin S and bind mRNA molecules. Moreover, we demonstrated that mRNAs colocalized with FXR1 amyloid particles are completely resistant to treatment with RNAse A. Taking into consideration that the members of ribonuclease A superfamily function in neurons (3) we can conclude that amyloid conformers of FXR1 control RNA stability in brain. Thus, in contrast to pathological amyloids that cause neurodegeneration, FXR1 is the functional amyloid in forebrain. We showed that amyloid properties of FXR1 depend on its N-terminal part from 1 to 379 amino acids. This fragment forms amyloid fibrils in vitro that bind Congo red and manifest apple-green birefringence when assayed by polarization microscopy. The amyloid-forming region of FXR1 is highly conserved in mammals. These data suggest that the ability of amyloid conformers of FXR1 to protect mRNAs is characteristic of different mammalian species, including humans. Significance StatementAmyloids are highly ordered cross-{beta} sheet protein fibrils associated with many neurodegenerative diseases including Alzheimers disease. However, some amyloid proteins regulate vital processes. We identified a set of proteins that form amyloid-like aggregates in the brain of healthy rats. One of them - the FXR1 protein is known to regulate memory and emotions. FXR1 forms amyloid fibrils that bind RNA molecules and prevent their degradation in brain cortex neurons. Amyloid-forming sequence of FXR1 is highly conserved across mammals including human. Discovery of functional amyloids in mammalian brain shows that strategy aimed at the development of universal anti-amyloid drugs is unpromising. Such potential drugs should prevent or suppress formation of pathological aggregates of a certain protein, but not affect functional amyloids.

neuroscience↗