TY - JOUR
T1 - Frizzled 1 and Wnt1 as new potential therapeutic targets in the traumatically injured spinal cord
AU - González, Pau
AU - González-Fernández, Carlos
AU - Campos-Martín, Yolanda
AU - Mollejo, Manuela
AU - Carballosa-Gautam, Melissa
AU - Marcillo, Alexander
AU - Norenberg, Michael
AU - Rodríguez, Francisco Javier
N1 - Funding Information:
We would like to thank Virginia Pérez, Sandra Vázquez, and the technical staff from the Service of Microscopy and Image Analysis and the Service of Flow Cytometry at the National Hospital for Paraplegics for their outstanding technical help, especially to Javier Mazarío for his essential participation in the design of the automatized cell count method. We also like to thank Sam David for his help to obtain the lesioned human spinal cord samples. This work has been supported by the Fondo de Investigación Sanitaria (FIS) of Instituto de Salud Carlos III (Grant number PI12/2895; FEDER co-funded) and the Ministerio de Ciencia, Innovación y Universidades (Grant number RTI2018-097775-B-I00; FEDER co-funded).
Funding Information:
We would like to thank Virginia P?rez, Sandra V?zquez, and the technical staff from the Service of Microscopy and Image Analysis and the Service of Flow Cytometry at the National Hospital for Paraplegics for their outstanding technical help, especially to Javier Mazar?o for his essential participation in the design of the automatized cell count method. We also like to thank Sam David for his help to obtain the lesioned human spinal cord samples. This work has been supported by the Fondo de Investigaci?n Sanitaria (FIS) of Instituto de Salud Carlos III (Grant number PI12/2895; FEDER co-funded) and the Ministerio de Ciencia, Innovaci?n y Universidades (Grant number RTI2018-097775-B-I00; FEDER co-funded).
Publisher Copyright:
© 2020, Springer Nature Switzerland AG.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/11/1
Y1 - 2020/11/1
N2 - Despite the experimental evidence pointing to a significant role of the Wnt family of proteins in physiological and pathological rodent spinal cord functioning, its potential relevance in the healthy and traumatically injured human spinal cord as well as its therapeutic potential in spinal cord injury (SCI) are still poorly understood. To get further insight into these interesting issues, we first demonstrated by quantitative Real-Time PCR and simple immunohistochemistry that detectable mRNA expression of most Wnt components, as well as protein expression of all known Wnt receptors, can be found in the healthy human spinal cord, supporting its potential involvement in human spinal cord physiology. Moreover, evaluation of Frizzled (Fz) 1 expression by double immunohistochemistry showed that its spatio-temporal and cellular expression pattern in the traumatically injured human spinal cord is equivalent to that observed in a clinically relevant model of rat SCI and suggests its potential involvement in SCI progression/outcome. Accordingly, we found that long-term lentiviral-mediated overexpression of the Fz1 ligand Wnt1 after rat SCI improves motor functional recovery, increases myelin preservation and neuronal survival, and reduces early astroglial reactivity and NG2+ cell accumulation, highlighting the therapeutic potential of Wnt1 in this neuropathological situation.
AB - Despite the experimental evidence pointing to a significant role of the Wnt family of proteins in physiological and pathological rodent spinal cord functioning, its potential relevance in the healthy and traumatically injured human spinal cord as well as its therapeutic potential in spinal cord injury (SCI) are still poorly understood. To get further insight into these interesting issues, we first demonstrated by quantitative Real-Time PCR and simple immunohistochemistry that detectable mRNA expression of most Wnt components, as well as protein expression of all known Wnt receptors, can be found in the healthy human spinal cord, supporting its potential involvement in human spinal cord physiology. Moreover, evaluation of Frizzled (Fz) 1 expression by double immunohistochemistry showed that its spatio-temporal and cellular expression pattern in the traumatically injured human spinal cord is equivalent to that observed in a clinically relevant model of rat SCI and suggests its potential involvement in SCI progression/outcome. Accordingly, we found that long-term lentiviral-mediated overexpression of the Fz1 ligand Wnt1 after rat SCI improves motor functional recovery, increases myelin preservation and neuronal survival, and reduces early astroglial reactivity and NG2+ cell accumulation, highlighting the therapeutic potential of Wnt1 in this neuropathological situation.
KW - Frizzled 1
KW - Human
KW - Rat
KW - Spinal cord injury
KW - Wnt
KW - Wnt1
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U2 - 10.1007/s00018-019-03427-4
DO - 10.1007/s00018-019-03427-4
M3 - Article
C2 - 31900623
AN - SCOPUS:85077578685
VL - 77
SP - 4631
EP - 4662
JO - Cellular and Molecular Life Sciences
JF - Cellular and Molecular Life Sciences
SN - 1420-682X
IS - 22
ER -