Abstract
The hippocampus encodes spatial and contextual information involved in memory and learning. The incorporation of new neurons into hippocampal networks increases neuroplasticity and enhances hippocampal-dependent learning performances. Only few studies have described hippocampal abnormalities after spinal cord injury (SCI) although cognitive deficits related to hippocampal function have been reported in rodents and even humans. The aim of this study was to characterize in further detail hippocampal changes in the acute and chronic SCI. Our data suggested that neurogenesis reduction in the acute phase after SCI could be due to enhanced death of amplifying neural progenitors (ANPs). In addition, astrocytes became reactive and microglial cells increased their number in almost all hippocampal regions studied. Glial changes resulted in a non-inflammatory response as the mRNAs of the major pro-inflammatory cytokines (IL-1β, TNFα, IL-18) remained unaltered, but CD200R mRNA levels were downregulated. Long-term after SCI, astrocytes remained reactive but on the other hand, microglial cell density decreased. Also, glial cells induced a neuroinflammatory environment with the upregulation of IL-1β, TNFα and IL-18 mRNA expression and the decrease of CD200R mRNA. Neurogenesis reduction may be ascribed at later time points to inactivation of neural stem cells (NSCs) and inhibition of ANP proliferation. The number of granular cells and CA1 pyramidal neurons decreased only in the chronic phase. The release of pro-inflammatory cytokines at the chronic phase might involve neurogenesis reduction and neurodegeneration of hippocampal neurons. Therefore, SCI led to hippocampal changes that could be implicated in cognitive deficits observed in rodents and humans.
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We thank Dr. Soraya Martín-Suárez for invaluable technical help.
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This work was funded by the grants RyC-2012–11137 (MINECO) and SAF-2015–70866-R (MINECO with FEDER funds) to JME. IJ received The Boehringer Ingelheim Travel Grant to support the internship to the Laboratory of Neural Stem Cells and Neurogenesis in the Achucarro Basque Center for Neuroscience, Leioa Spain. This work was also supported by a grant from the Argentine Ministry of Science and Technology (PICT 2017 Nº0509) granted to FL. These funding sources did not have a role in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.
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FL and JME wrote the manuscript and designed the experiments. IJ collected and analyzed the data. AFDN reviewed and edited the manuscript. All authors read and approved the final manuscript.
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10571_2020_900_MOESM1_ESM.tif
Fig. 1: The number of NeuN+ neurons remained unchanged after Spinal cord injury (SCI) in both the granular cell layer (GCL) and CA1 at 7 days post-injury (dpi). Two-way ANOVA followed by Bonferroni post-test. (TIF 112 kb)
10571_2020_900_MOESM2_ESM.tif
Fig. 2: The number of total astrocytes remained unchanged after Spinal cord injury (SCI) at 7 and 50 days post injury (dpi) in the SGZ and granular cell layer (GCL) (a), hilus (b), Molecular layer (c) and Stratum Radiatum (d). Two-way ANOVA followed by Bonferroni post-test. (TIF 511 kb)
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Jure, I., De Nicola, A.F., Encinas, J.M. et al. Spinal Cord Injury Leads to Hippocampal Glial Alterations and Neural Stem Cell Inactivation. Cell Mol Neurobiol 42, 197–215 (2022). https://doi.org/10.1007/s10571-020-00900-8
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DOI: https://doi.org/10.1007/s10571-020-00900-8