Amazing stuff! Good news!
"Doctors use ketamine on patients as general anesthesia before surgery. They also prescribe it in low doses for pain management, and more recently, it’s been used for treatment-resistant depression where other drugs have failed.
It works by dampening communication between brain cells. But a new study reveals that its effects on the brain are different in male and female mice. This insight—if reproduced in humans—could change the way we test the efficacy of drugs and unlock better treatments for depression. ...
discovered that when female mice are recovering from a single ketamine sedation, their brains become more active than their male counterparts, specifically their microglia. These specialized brain cells began reaching out with their branch-like arms to intermingle with surrounding brain cells. This increased activity led to the removal of the extracellular matrix—the proteins and molecules surrounding, supporting, and giving structure to cells—and created space that allowed new synapses to form and remodel the neural network, thereby increasing neuroplasticity. Researchers didn’t observe this behavior in male mice. ...
Neuroplasticity is a delicate balance: too much or too little have both been linked to neuropsychiatric disorders. ..."
From the abstract:
"Anesthesia recovery is critical for resuming normal physiological and neuronal functions; however, the mechanisms involved remain elusive.
Here, we identify a female-selective corticosterone-mediated microglia-neuron interaction during ketamine anesthesia recovery, absent in males.
This microglia-neuron interaction induces plastic and functional neuronal changes, as evidenced by increased mEPSC frequency, which was occluded upon microglia depletion.
We showed that this process is driven through up-regulation of the stress-responsive co-chaperone Fkbp5 mRNA and its protein, Fkbp51, in female microglia. Fkbp5/Fkbp51 is a key intermediary in a corticosteroid-induced stress response, and its involvement points toward a critical interface between endocrine signaling and microglia.
To counteract the observed ketamine anesthesia-mediated increase in blood corticosterone during recovery, we removed the primary source of corticosterone by adrenalectomy. Close microglia-neuron interaction was reduced and increased again following corticosterone injection.
Our findings identify a sex-specific microglia-mediated mechanism of neuronal plasticity during anesthesia recovery, driven by corticosterone, thereby enhancing our understanding of sex differences in brain function."
Corticosterone-linked microglial activity underpins sexually dimorphic neuroplasticity after ketamine anesthesia (open access)
Distribution of microglia (green) across the different cortical layers (orange) in the mouse visual cortex
Fig. 1. Female microglia interact with neurons, promoting spinogenesis and plasticity upon ketamine recovery.
