Frizzled 1 and Wnt1 as new potential therapeutic targets in the traumatically injured spinal cord

• DOI: 10.1007/s00018-019-03427-4
• Publication Date: 2020-01-03T15:03:05Z
• Authors: Pau González; Carlos González-F...; Yolanda Campos-Ma...; Manuela Mollejo; Melissa Carballos...; Alexander Marcillo; Michael Norenberg; Francisco Javier ...
• Keywords: 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

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.