Custom made python script using network assignment and scoring to estimate the impact of biological processes.

Blood-borne factors are essential to maintain neuronal synaptic plasticity
and cognitive resilience throughout life. One such factor is osteocalcin
(OCN), a pro-youthful hormone produced by bones, that influences
hippocampal neuronal homeostasis. However, the way how this blood-borne
factor communicates with neurons remains unclear. Here, we show the
importance of a core primary cilium (PC)-protein/autophagy axis in
mediating OCN's effects. We found that OCN’s receptor, GPR158, is
present at the PC of hippocampal neurons and mediates the regulation of
autophagy machinery by OCN. During aging, autophagy and PC-core proteins
are reduced in neurons and restoring their levels is sufficient to improve
cognitive impairments in aged mice. Mechanistically, the induction of this
axis by OCN is dependent on the PC-dependent cAMP response element-binding
protein signaling pathway. Altogether, this study demonstrates that
PC/autophagy axis is a gateway to mediate blood-borne factor-neuron
communication and advances our understanding of the mechanism involved in
age-related cognitive decline.