Amazing stuff (but a little bit aged news)!
"... In a recent study, a team of neurologists has now traced a pathway back to cells called astrocytes located in the amygdala, the region of the brain responsible for processing emotions. ...
But in chronically stressed mice, the researchers found that these cells rapidly age, preventing them from properly communicating with other neurons . As a result, mice with damaged astrocytes showed heightened activity in the amygdala, which is closely associated with both anxiety and with decreased insulin production (and thus higher blood glucose levels).
The researchers were able to reverse the effects of cellular aging by providing the mice with senolytic drugs that target senescent cells or by supplementing their diets with L-serine, an amino acid important for establishing the link between astrocytes and neurons. ..."
From the highlights and abstract:
"Highlights
• [Chronic stress] lowers amygdaloid astrocytic HK2 via PBX1, driving cellular senescence
• Astrocytic HK2 deficiency limits the “serine shuttle” and disrupts synaptic stability
• Stress shifts amygdala output to sympathetic bias, promoting hyperglycemia
• L-serine or dasatinib/quercetin restores neurobehavior and blood glucose homeostasis
Summary
Chronic stress (CS) exacerbates anxiety and hyperglycemia, emerging as a key risk factor for type 2 diabetes, yet the mechanism remains unclear.
Here, we found that CS induces hyperglycemia and enhanced amygdaloid astrocytic senescence in mice.
The amygdaloid astrocytic senescence was mediated by the reduction of hexokinase 2 (HK2) driven by pre-B cell leukemia homeobox transcription factor 1 (PBX1). The astrocytic Hk2 deletion mice and amygdala-specific astrocytic Hk2 knockdown mice both display anxiety-like behaviors and hyperglycemia.
The reduction of HK2 in astrocytes reduces L-serine synthesis and decreases the supply to neurons for the generation of D-serine by disrupting the astrocyte-neuron serine shuttle.
Reduced neuronal D-serine level in the amygdala impaired the balance of sympathetic and parasympathetic amygdala-pancreas projections, leading to hyperglycemia.
L-serine supplementation or dasatinib/quercetin administration to eliminate senescent cells alleviates both CS-induced neurobehaviors and peripheral hyperglycemia.
Together, these findings reveal that HK2 in amygdaloid astrocytes mediates CS-induced neurobehaviors and hyperglycemia."
Graphical abstract
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