Figure 1.

Graphical depiction of two possible mechanisms by which reelin down-regulation may be involved in the pathophysiology of depression. (A) Reelin secreted by some hippocampal GABAergic interneurons in the dentate subgranular zone (SGZ) as well as in cells in the distal molecular layer (shown in red) is involved in hippocampal neurogenesis, particularly the rate and extent of dendritogenesis of newborn granule cells (shown in blue). Repeated CORT administration reduces the number of reelin+ cells in the dentate SGZ and the amount of extracellular reelin in the distal molecular layer, which delays the maturation (e.g., reduced dendritogenesis) of newborn neurons. These neurons may fail to properly integrate into existing hippocampal circuits. (B) Reelin secreted by GABAergic interneurons promotes and stabilizes synapses impinging onto dendritic spines. The downregulation and neurochemical alterations of reelin-positive cells in the distal molecular layer and CA1 stratum-lacunosum-moleculare (shown in red) instigated by chronic stress would decrease in the number of dendritic spines, resulting in a loss of glutamatergic synaptic strength and possibly a dampening of neurotransmitter release from glutamatergic terminals (shown in blue). This would further affect hippocampal circuitry.