Journal of Clinical Investigation
December 15, 2022
Q. Ru, Yungang Lu, Ali Bin Saifullah et al.
Chronic pain often leads to depression, increasing patient suffering and worsening prognosis. While hyperactivity of the anterior cingulate cortex (ACC) appears to be critically involved, the molecular mechanisms underlying comorbid depressive symptoms in chronic pain remain elusive. T cell lymphoma invasion and metastasis 1 (Tiam1) is a Rac1 guanine nucleotide exchange factor (GEF) that...
Journal of Clinical Investigation
June 22, 2020
Y. Hurd
The past decade has seen a reduction in society’s perception of cannabis being of any risk or harm. However, we are in a transformational time in which cannabis’ health implications related to neurodevelopment, particularly for vulnerable populations, must challenge such perceptions of harmlessness. The combination of multiple interrelated factors — societal, political, and business — have...
Journal of Clinical Investigation
November 19, 2019
Danielle M. Gerhard, Santosh Pothula, Rong-Jian Liu et al.
345 citations
A single sub-anesthetic dose of ketamine, an NMDA receptor (NMDAR) antagonist, produces rapid and sustained antidepressant actions in depressed patients, addressing a major unmet need for the treatment of mood disorders. Ketamine produces a rapid increase in extracellular glutamate and synaptic formation in the prefrontal cortex, but the initial cellular trigger that initiates these and its...
Journal of Clinical Investigation
April 16, 2019
T. Kato, Santosh Pothula, Rong-Jian Liu et al.
88 citations
Preclinical studies demonstrate that rapid acting antidepressants, including ketamine require stimulation of mTORC1 signaling. This pathway is regulated by neuronal activity, endocrine and metabolic signals, notably the amino acid leucine, which activates mTORC1 signaling via binding to the upstream regulator sestrin. Here, we examined the antidepressant actions of NV-5138, a novel highly...