Review article
Neuroprotective effect of antidepressant and mood-stabilizing drugs

The pathway of the pathogenic and therapeutic concepts of affective illnesses in recent decades has evolved from disturbances of synaptic neurotransmission in the central nervous system (CNS), and their regulation, to disturbances of neural activity and restoring its normal function (neuroprotective action). A molecular and cellular theory of depression was proposed in 1997, claiming disturbances of neural plasticity in the pathogenesis of depression, such as atrophy of hippocampal cells, diminished expression of neurotrophic factors and impairment of neurogenesis. The changes are stress-induced and occur in persons with genetic predisposition. Antidepressant drugs counteract these processes by preventing ”toxic” action of hypercortisolaemia on hippocampal cells, causing increased expression of neurotrophic factors, especially brain-derived neurotrophic factor (BDNF), and stimulation of neurogenesis. Evidence has also been accumulated in recent years for neuroprotective properties of mood-stabilizing drugs (mainly lithium and valproate), which may play a role in the therapeutic action of these drugs in bipolar affective illness. Neuroprotective effects of these drugs are probably related to their effect on intracellular signalling, such as phosphatidylinositol system, protein kinase C activity, neuroprotective factor bcl-2 and glycogen 3-beta synthase, as well as increased expression of BDNF and stimulation of neurogenesis. Increasing data have also pointed to neuroprotective properties of novel (atypical) neuroleptic drugs, which exert mood-stabilizing effect. These properties include prevention of apoptosis, increased expression of neurotrophic factors and increased neurogenesis.