Comparative significancea of the main indicators of basic neurobiological processes across the three stages analyzed (Younger, Elder, and MCI groups)
| Functionality | Younger | Elder | MCI |
|---|---|---|---|
| NTRKs signaling | 8.97 | 6.68 | 0 |
| GDNF/RET signaling | 1.49 | 0 | 2.76 |
| Neuroinflammatory response | 2.95 | 5.39 | 0 |
| Cellular response to stress | 3.40 | 4.09 | 0 |
| Regulation of stress response | 2.43 | 2.96 | 0 |
| MAPK cascade | 6.95 | 3.23 | 2.57 |
| Stress-activated MAPK cascade | 1.84 | 1.77 | 0 |
| Response to hypoxia | 6.95 | 5.19 | 0 |
| Response to oxidative stress | 1.97 | 2.79 | 0 |
| Cellular response to Abeta peptide | 5.30 | 6.97 | 5 |
| Positive amyloid fibril formation | 2.01 | 3.35 | 0 |
| ER stress & response to unfolded proteins | 0 | 3.08 | 0 |
| Intrinsic apoptosis in ER stress | 0 | 4.69 | 0 |
| Osmotic stress | 0 | 1.84 | 0 |
| Response to glucocorticoids | 1.70 | 6.59 | 0 |
| MeCP2 transcriptional regulation | 6.39 | 5.32 | 3.79 |
| DREAM pathway | 4.61 | 2.35 | 0 |
| Transcription regulation by NPAS4 | 5.47 | 2.74 | 0 |
| Sumoylation of intracellular receptors | 2.30 | 2.96 | 0 |
| CNS development | 12.52 | 13.32 | 0 |
| Pattern specification (GO: 0007389) | 1.83 | 4.83 | 0 |
| Gliogenesis | 5.65 | 9.16 | 1.37 |
| Astrocyte projection | 3.53 | 1.84 | 0 |
| Astrocyte activation | 2.54 | 4.84 | 1.46 |
| Neurogenesis (positive regulation) | 3.92 | 4.50 | 3.04 |
| Neurogenesis (negative regulation) | 2.57 | 2.26 | 0 |
| Cell fate commitment | 0 | 3.44 | 0 |
| Dendrite development | 7.59 | 6.59 | 0 |
| Dendrite spine organization | 7.27 | 3 | 1.37 |
| Axonogenesis | 11.99 | 9.48 | 1.37 |
| Collateral sprouting | 4.27 | 4.15 | 1.60 |
| Response to axon injury | 1.77 | 2.77 | 1.33 |
| CA3-pyramidal cell dendrites | 1.45 | 0 | 1.86 |
| Hippocampal mossy fibers (DG-CA3) | 3.05 | 1.63 | 0 |
| CA1-Schaffer collateral synapses | 2.62 | 1.84 | 3.45 |
| Fear response | 4.87 | 2.54 | 1.60 |
| Rhythm process | 4.46 | 6.12 | 1.76 |
a The significance is expressed as –log10 (FDR), where FDR is the false discovery rate. ER: endoplasmic reticulum; NTRKs: neurotrophic tropomyosin-receptor kinases; NPAS4: neuronal PAS domain protein 4; CA: cornu ammonis; DG: dentate gyrus. Note that a zero value denotes a non-significant functionality, as FDR = 1 (For details of the genes involved see Tables S1–S3)