New perspective on sustained antidepressant effect: focus on neurexins regulating synaptic plasticity
Cell Death Discovery – May 01, 2024
Source: OpenAlex
Summary
Lasting relief from depression may stem from new understandings of brain function. Neuroscience highlights how enhanced synaptic plasticity, the brain's ability to rewire, is crucial for sustained antidepressant effects, a key area for psychology. Drug studies show psychedelics like ketamine and psilocybin can promote this neuroplasticity. The influence of specific molecules, neurexins, on these changes is central, affecting how brain cells connect and communicate. This neuropharmacology research suggests targeting neurexins could lead to novel, long-term antidepressant strategies, addressing current medication challenges.
Abstract
Abstract Depression is highly prevalent globally, however, currently available medications face challenges such as low response rates and short duration of efficacy. Additionally, depression mostly accompany other psychiatric disorders, further progressing to major depressive disorder without long-term effective management. Thus, sustained antidepressant strategies are urgently needed. Recently, ketamine and psilocybin gained attention as potential sustained antidepressants. Review of recent studies highlights that synaptic plasticity changes as key events of downstream long-lasting changes in sustained antidepressant effect. This underscores the significance of synaptic plasticity in sustained antidepressant effect. Moreover, neurexins, key molecules involved in the regulation of synaptic plasticity, act as critical links between synaptic plasticity and sustained antidepressant effects, involving mechanisms including protein level, selective splicing, epigenetics, astrocytes, positional redistribution and protein structure. Based on the regulation of synaptic plasticity by neurexins, several drugs with potential for sustained antidepressant effect are also discussed. Focusing on neurexins in regulating synaptic plasticity promises much for further understanding underlying mechanisms of sustained antidepressant and the next step in new drug development. This research represents a highly promising future research direction.