Frizzled 1 and Wnt1 as new potential therapeutic targets in the traumatically injured spinal cord
Adult
Aged, 80 and over
Male
Neurons
0301 basic medicine
0303 health sciences
Adolescent
Recovery of Function
Wnt1 Protein
Middle Aged
Frizzled Receptors
Rats
3. Good health
Disease Models, Animal
03 medical and health sciences
HEK293 Cells
Spinal Cord
Animals
Humans
Female
Rats, Wistar
Spinal Cord Injuries
Aged
DOI:
10.1007/s00018-019-03427-4
Publication Date:
2020-01-03T15:03:05Z
AUTHORS (8)
ABSTRACT
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.
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