Sublayer- and cell-type-specific neurodegenerative transcriptional trajectories in hippocampal sclerosis

Autor: Aixa V. Morales, Yasunori Hayashi, Liset Menendez de la Prida, Masaaki Sato, Beatriz Gal, José P. López-Atalaya, Ivan Fernandez-Lamo, Angel Barco, Carmen M. Navarrón, Rita Reig-Viader, Manuel Valero, Angel Marquez-Galera, Daniel C. Medeiros, Elena Cid, Luis Ballesteros-Esteban, Daniel Gomez-Dominguez, Àlex Bayés
Přispěvatelé: Ministerio de Ciencia e Innovación (España), Fundación Tatiana Pérez de Guzmán el Bueno, Human Frontier Science Program, Ministerio de Ciencia, Innovación y Universidades (España), Ministerio de Economía y Empresa (España), Fundación Alicia Koplowitz
Rok vydání: 2021
Předmět:
0301 basic medicine
Enfermedad del sistema nervioso
Hippocampus
Transcriptome
Mice
Epilepsy
RNAscope
0302 clinical medicine
sharp-wave ripples
Temporal lobe epilepsy
temporal lobe epilepsy
Neurons
Single-cell
Cell adhesion molecule
Neurodegeneration
Neurodegenerative Diseases
epilepsy
Single-nucleus
RNAseq
Synaptic signaling
Immediate early gene
Célula
Cell type
In vivo recordings
in vivo recordings
Biology
General Biochemistry
Genetics and Molecular Biology
Temporal lobe
Epilepsia
single-cell
03 medical and health sciences
medicine
Animals
Humans
single-nucleus RNAseq
Cell adhesion
Hippocampal sclerosis
Calbindin
Sclerosis
fast ripples
calbindin
Sharp-wave ripples
medicine.disease
Fast ripples
Gene expression profiling
030104 developmental biology
Neuroscience
030217 neurology & neurosurgery
Esclerosis amiotrófica lateral
Zdroj: Digital.CSIC. Repositorio Institucional del CSIC
instname
Cell Reports
r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
ABACUS. Repositorio de Producción Científica
Universidad Europea (UEM)
CELL REPORTS
r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante
ISSN: 2018-0985
2211-1247
DOI: 10.1101/2021.02.03.429560
Popis: Hippocampal sclerosis, the major neuropathological hallmark of temporal lobe epilepsy, is characterized by different patterns of neuronal loss. The mechanisms of cell-type-specific vulnerability and their progression and histopathological classification remain controversial. Using single-cell electrophysiology in vivo and immediate-early gene expression, we reveal that superficial CA1 pyramidal neurons are overactive in epileptic rodents. Bulk tissue and single-nucleus expression profiling disclose sublayer-specific transcriptomic signatures and robust microglial pro-inflammatory responses. Transcripts regulating neuronal processes such as voltage channels, synaptic signaling, and cell adhesion are deregulated differently by epilepsy across sublayers, whereas neurodegenerative signatures primarily involve superficial cells. Pseudotime analysis of gene expression in single nuclei and in situ validation reveal separated trajectories from health to epilepsy across cell types and identify a subset of superficial cells undergoing a later stage in neurodegeneration. Our findings indicate that sublayer- and cell-type-specific changes associated with selective CA1 neuronal damage contribute to progression of hippocampal sclerosis.
This work was supported by grants from MICINN (RTI2018-098581-B-I00 to L.M.P.), Fundación Tatiana Pérez de Guzman el Bueno, and the SynCogDis Network (SAF2014-52624-REDT and SAF2017- 90664-REDT to L.M.P. and A. Bayes). Collaboration between L.M.d.l.P. and Y.H. was supported by Human Frontiers Science Program (HFSP) grant RGP0022/2013. J.P.L.-A. was supported by grants from MICIU co-financed by ERDF (RYC-2015-18056 and RTI2018-102260-B-I00) and Severo Ochoa grant SEV-2017-0723. R.R.-V. and A. Bayes were supported by MINECO BFU2015-69717-P and RTI2018-097037-B-100 and a Marie Curie career integration grant (ref. 304111). A.V.M. was supported by MICINN (SAF2017- 85717-R) and Fundación Alicia Koplowitz. A. Barco was supported by grants SAF2017-87928-R from MICINN co-financed by ERDF and RGP0039/2017 from the Human Frontiers Science Program Organization. The Instituto de Neurociencias is a ‘‘Centre of Excellence Severo Ochoa.’’ D.G.-D. and C.M.N. hold PhD fellowships from MICINN (BES-2013-064171 and BES2016-076281, respectively).
Databáze: OpenAIRE
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