Prosaposin and its receptors GRP37 and GPR37L1 show increased immunoreactivity in the facial nucleus following facial nerve transection

Abstract

Neurotrophic factor prosaposin (PS) is a precursor for saposins A, B, C, and D, which are activators for specific sphingolipid hydrolases in lysosomes. Both saposins and PS are widely contained in various tissues. The brain, skeletal muscle, and heart cells predominantly contain unprocessed PS rather than saposins. PS and PS-derived peptides stimulate neuritogenesis and increase choline acetyltransferase activity in neuroblastoma cells and prevent programmed cell death in neurons. We previously detected increases in PS immunoactivity and its mRNA in the rat facial nucleus following facial nerve transection. PS mRNA expression increased not only in facial motoneurons, but also in microglia during facial nerve regeneration. In the present study, we examined the changes in immunoreactivity of the PS receptors GPR37 and GPR37L1 in the rat facial nucleus following facial nerve transection. Following facial nerve transection, many small Iba1- and glial fibrillary acidic protein (GFAP)-positive cells with strong GPR37L1 immunoreactivity, including microglia and astrocytes, were observed predominately on the operated side. These results indicate that GPR37 mainly works in neurons, whereas GPR37L1 is predominant in microglia or astrocytes, and suggest that increased PS in damaged neurons stimulates microglia or astrocytes via PS receptor GPR37L1 to produce neurotrophic factors for neuronal recovery.

C5aR1 antagonism alters microglial polarization and mitigates disease progression in a mouse model of Alzheimer’s disease

“…Patients lacking prosaposin presented increase in reactive astrocytes and lack of mature oligodendrocytes and cortical neurons [ 78 , 79 ]. The Psap-Gpr37l1 signaling has been described to induce production of neurotropic factors by microglia for neuronal recovery [ 80 ]. Our single cell signaling inference results suggest that PMX205 treatment increases prosaposin signaling secreted from disease associated microglia targeting other microglial subtypes that express Gpr37l1.…”

The expression of prosaposin and its receptors, GRP37 and GPR37L1, are increased in the developing dorsal root ganglion

“…Neuro- and glio-protection by PSAP is mediated by GPR37 and GPR37L1 [ 24 , 25 ], although the interactions of these receptors with PSAP have yet to be universally acknowledged [ 26 ]. We previously showed increased GPR37 and GPR37L1 in astrocytes and microglia, as well as in neurons in the facial nucleus, following transection of the facial nerves [ 27 ].…”

C5aR1 antagonism alters microglial polarization and mitigates disease progression in a mouse model of Alzheimer’s disease

“…Patients lacking prosaposin presented increase in reactive astrocytes and lack of mature oligodendrocytes and cortical neurons ( 67, 68 ). The Psap-Gpr37l1 signaling has been described to induce production of neurotropic factors by microglia for neuronal recovery ( 69 ). Our single cell signaling inference results suggest that PMX205 treatment increases prosaposin signaling secreted from disease associated microglia targeting other microglial subtypes that express Gpr37l1.…”