Table 2 Loss of oligo- and astroglial cells in SCZ. A comparison between OLs, OPCs and ACs.
Sources, impact on pathophysiology, and therapy options | OLs | OPCs | ACs |
|---|---|---|---|
Presence of glial cell deficits | Replicated findings from different laboratories point to prominent cell losses in different brain areas [7, 19,20,21,22,23, 71,72,73,74,75,76, 79,80,81,82]. | Deficits arising from failure of OPCs to become myelinating OLs and/or deficits from loss of differentiating OPCs (reduced number of clusters containing differentiating OPCs) [23, 35, 72]. | Controversially discussed. A number of GFAP based studies showed mild cell losses in different brain areas [18, 24, 26, 27, 154, 169]. No AC deficits as a consequence of disturbed AC differentiation or maturation [9, 175,176,177,178]. |
Cell pathological process leading to cell loss | Atrophy (?) Degeneration (?) | ||
Influence of medication | No significant influence of haloperidol on OL death in monkeys [97]. However, treatment with haloperidol and clozapine causes chemical alterations in human cultured OLs [94, 95]. Quetiapine enhances OL regeneration and myelin repair after cuprizone-induced demyelination [98]. | Antipsychotics promote the differentiation of OPCs by regulating the transcription factors OLIG 1 and OLIG2 [118]. Olanzapine increased the numbers of new-born cells differentiating to the OL lineage but not the neuronal lineage [123]. Olanzapine stimulates proliferation but inhibits differentiation of cultured rat OPC [124]. Haloperidol activates quiescent OPCs in the adult mouse brain [125]. Quetiapine modulates OPC cell cycle and thereby facilitates OL differentiation [126, 127]. Haloperidol and clozapine have protective effects on energy-deprived OLN-93 OLs [128]. | Haloperidol induces AC death in monkeys and cytotoxicity in human ACs in culture [97, 179, 180]. |
Putative impact on pathophysiology | Contributes to myelin loss [11, 46, 52, 54], Impairment of higher brain functions (including cognition) [37, 99], Influence on glutamatergic and dopaminergic neurotransmission [100,101,102]. | Might significantly contribute to myelin loss. Possible influence on interneuron migration. Impairment of higher brain functions (including cognition). | Might contribute to disturbed neocortical neuron-glia interaction [18, 37, 99]. |
Possible therapeutic options in addition to antipsychotics | Antidepressants [188], Resveratrol [180], Aerobic exercise alone or in combination with clemastine [37, 39, 211], Engrafting of healthy cells [212]? | D-aspartate [199], Aerobic exercise [37, 39, 211], Engrafting of healthy cells [212]? | Antidepressants [188], Resveratrol [180], Aerobic exercise [37, 39, 211], Engrafting of healthy cells [212]? |
