The role of ketamine in major depressive disorders: Effects on parvalbumin-positive interneurons in hippocampus

BARRUTIETA-ARBERAS, I; ORTUZAR, N; VAQUERO-RODRÍGUEZ, A; PICÓ-GALLARDO, M; BENGOETXEA, H; GUEVARA, MA; GARGIULO, PA; LAFUENTE, JV

EXPERIMENTAL BIOLOGY AND MEDICINE

SOC EXPERIMENTAL BIOLOGY MEDICINE

Año: 2023

1535-3702

AbstractMajor depressive disorder (MDD) is a complex illness that is arising as a growingpublic health concern. Although several brain areas are related to this type ofdisorders, at the cellular level, the parvalbumin-positive cells of the hippocampusinterplay a very relevant role. They control pyramidal cell bursts, neuronalnetworks, basic microcircuit functions, and other complex neuronal tasks involvedin mood disorders. In resistant depressions, the efficacy of current antidepressanttreatments drops dramatically, so the new rapid-acting antidepressants (RAADs)are being postulated as novel treatments. Ketamine at subanesthetic doses andits derivative metabolites have been proposed as RAADs due to their rapid andsustained action by blocking N-methyl-d-aspartate (NMDA) receptors, which in turnlead to the release of brain-derived neurotrophic factor (BDNF). This mechanismproduces a rapid plasticity activation mediated by neurotransmitter homeostasis,synapse recovery, and increased dendritic spines and therefore, it is a promisingtherapeutic approach to improve cognitive symptoms in MDD.Keywords: N-methyl-d-aspartate receptors (NMDARs), ketamine, interneurons (INs), major depressive disorder (MDD), brain-derived neurotrophic factor (BDNF), hippocampus (HC)