Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
January 1, 2024
Jihye Kim, Michelle J He, Alina K Widmann et al.
47 citations
Neurotrophic factors help neurons grow, survive, and connect. For decades, scientists thought that too little neurotrophic support caused the loss of synapses and cells seen in psychiatric disorders. Traditional antidepressants raise neurotrophic levels over weeks, matching when they start working. Newer treatments like ketamine and psychedelics work within hours and quickly release neurotrophins into synapses. This has changed how researchers understand neurotrophins and their receptors. This review discusses these new insights into receptor signaling and their clinical importance, building on what is already known about neurotrophic factors in psychiatric disorders and treatments.
Cell
April 30, 2026
Hermany Munguba, Anisul Arefin, Ryota Hasegawa et al.
4 citations
Ketamine's rapid antidepressant effects depend on mu-opioid receptors (MORs) located on somatostatin-expressing interneurons in the medial prefrontal cortex. Chronic stress causes these interneurons to become hypertrophic, leading to excessive inhibition of pyramidal neurons, a disruption that ketamine reverses. By identifying GPCRs enriched in these interneurons through RNA sequencing, the authors validate several antidepressant targets and show that activating multiple GPCRs synergistically produces potent antidepressant-like effects with fewer side effects. This approach offers a general strategy for discovering GPCR-based treatments for brain disorders.
Science advances
May 1, 2026
Anisul Arefin, Jihye Kim, Manas Pratim Chakraborty et al.
1 citation
Ketamine's antidepressant effects depend on the interplay between two types of neuromodulatory receptors: TrkB and mGluR5. mGluR5 amplifies BDNF-driven signaling through TrkB, enabling synaptic potentiation, while BDNF activation of TrkB drives mGluR5 endocytosis, impairing synaptic depression. Ketamine enhances these interactions by increasing surface and postsynaptic levels of TrkB. An mGluR5 positive allosteric modulator can further boost both modes of cross-talk and enhance ketamine's effects, revealing that receptor-receptor interplay can drive therapeutic action.