Pharmacological Enhancement of Adult Hippocampal Neurogenesis Improves Behavioral Pattern Separation in Young and Aged Mice.

Background: Impairments in behavioral pattern separation (BPS)-the ability to distinguish between similar contexts or experiences-contribute to memory interference and overgeneralization seen in many neuropsychiatric conditions, including depression, anxiety, PTSD, dementia, and age-related cognitive decline. While BPS relies on the dentate gyrus and is sensitive to changes in adult hippocampal neurogenesis (AHN), its significance as a pharmacological target has not been tested.

Methods: In this study, we applied a human neural stem cell high-throughput screening cascade to identify compounds that increase human neurogenesis.

Ventral hippocampal molecular pathways and impaired neurogenesis associated with 5-HT₁A and 5-HT₁B receptors disruption in mice.

The serotonergic system has been widely implicated in stress related psychiatric disorders such as depression and anxiety. Generation of receptor knockout mice has offered a new approach to study processes underlying anxiety. For instance, knockout mice for both 5-HT(1A) and 5-HT(1B) receptors (5-HT(1A/1B)(-/-)) display an anxious phenotype, associated with robust physiological and neurochemical changes related to brain serotonin function.

Blockade of the high-affinity noradrenaline transporter (NET) by the selective 5-HT reuptake inhibitor escitalopram: an in vivo microdialysis study in mice.

Background And Purpose: Escitalopram, the S(+)-enantiomer of citalopram is the most selective 5-HT reuptake inhibitor approved. Although all 5-HT selective reuptake inhibitors (SSRIs) increase extracellular levels of 5-HT ([5-HT](ext)). some also enhance, to a lesser extent, extracellular levels of noradrenaline ([NA](ext)).

Implications of the functional integration of adult-born hippocampal neurons in anxiety-depression disorders.

Adult neurogenesis in the dentate gyrus of the hippocampus has gained considerable attention as a cellular substrate for both the pathophysiology and treatment of depression. Overall, the studies of adult hippocampal neurogenesis are still in their infancy because most of them explore only one stage of this process. Importantly, given the built-in homeostatic mechanisms that act at each stage during the progression from stem cells to mature neurons (proliferation, differentiation, maturation, survival), it is very difficult to extrapolate the efficiency of a drug on adult neurogenesis from analysis of one stage alone.