Cholinergic-neuroimmune modulation of attention deficits and impaired cognitive functioning reflect brain transcript changes
(A) Higher cognitive functions such as attention are impaired in delirium and involve the prefrontal cortex (1), innervated by cholinergic neuron projections from cholinergic brain nuclei of the basal forebrain (2) and extending to the cholinergic anti-inflammatory brain–spleen circuit of the vagus nerve (3). (B) Age-dependent decline of CHRM3, ACHE, CHRNA7, CHRFAM7A, and SLC5A7 transcripts in the frontal cortex, basal ganglia and spleen. GTEx datasets of male and female transcript levels (blue and pink dots) change with age in both sexes. Note significant decreases in the frontal cortex for CHRM3 (r = −0.23, P=0.0081), CHRNA7 (r = −0.28, P=0.003), and SLC5A7 (r = −0.24; P=0.008), and in basal ganglia for CHRM3 (r = −0.22; P=0.0078), ACHE (r = −0.18; P=0.030) and CHRNA7 (r = −0.24; P=0.004). No significant change was observed in the spleen. Correlation is calculated using Spearman’s correlation test and green lines reflect linear fit. Adjusted P-values are FDR corrected. Subject numbers per the age groups of 20, 30, 40, 50, 60, 70 years were 5, 2, 13, 52, 85, 7 for frontal cortex; 7, 2, 21, 66, 94, 11 for basal ganglia; and 11, 19, 41, 60, 32, 3 for spleen.