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Działanie neuroprotekcyjne leków przeciwdepresyjnych i normotymicznych

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Author(s): Janusz Rybakowski

Journal: Neuropsychiatria i Neuropsychologia
ISSN 1896-6764

Volume: 1;
Issue: 1;
Start page: 49;
Date: 2006;
Original page

Keywords: neuroprotection | neuronal plasticity | antidepressant drugs | mood-stabilizing drugs | atypical antipsychotic drugs

ABSTRACT
The pathway of the pathogenic and therapeutic conceptsof affective illnesses in recent decades has evolved fromdisturbances of synaptic neurotransmission in the centralnervous system (CNS), and their regulation, todisturbances of neural activity and restoring its normalfunction (neuroprotective action). A molecular and cellulartheory of depression was proposed in 1997, claimingdisturbances of neural plasticity in the pathogenesis ofdepression, such as atrophy of hippocampal cells, diminishedexpression of neurotrophic factors and impairmentof neurogenesis. The changes are stress-induced and occurin persons with genetic predisposition. Antidepressantdrugs counteract these processes by preventing ”toxic”action of hypercortisolaemia on hippocampal cells, causingincreased expression of neurotrophic factors, especiallybrain-derived neurotrophic factor (BDNF), andstimulation of neurogenesis. Evidence has also beenaccumulated in recent years for neuroprotective propertiesof mood-stabilizing drugs (mainly lithium and valproate),which may play a role in the therapeutic action of thesedrugs in bipolar affective illness. Neuroprotective effectsof these drugs are probably related to their effect onintracellular signalling, such as phosphatidylinositolsystem, protein kinase C activity, neuroprotective factorbcl-2 and glycogen 3-beta synthase, as well as increasedexpression of BDNF and stimulation of neurogenesis.Increasing data have also pointed to neuroprotectiveproperties of novel (atypical) neuroleptic drugs, whichexert mood-stabilizing effect. These properties includeprevention of apoptosis, increased expression ofneurotrophic factors and increased neurogenesis.

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