Prefrontal cortex astroglia modulate anhedonia-like behavior.
S A CodeluppiM XuY BansalA E LepackV DuricM ChowJ MuirR C BagotP LicznerskiS L WilberGerard SanacoraEtienne SibilleRonald S DumanChristopher PittengerSierra A CodeluppiPublished in: Molecular psychiatry (2023)
Reductions of astroglia expressing glial fibrillary acidic protein (GFAP) are consistently found in the prefrontal cortex (PFC) of patients with depression and in rodent chronic stress models. Here, we examine the consequences of PFC GFAP+ cell depletion and cell activity enhancement on depressive-like behaviors in rodents. Using viral expression of diphtheria toxin receptor in PFC GFAP+ cells, which allows experimental depletion of these cells following diphtheria toxin administration, we demonstrated that PFC GFAP+ cell depletion induced anhedonia-like behavior within 2 days and lasting up to 8 days, but no anxiety-like deficits. Conversely, activating PFC GFAP+ cell activity for 3 weeks using designer receptor exclusively activated by designer drugs (DREADDs) reversed chronic restraint stress-induced anhedonia-like deficits, but not anxiety-like deficits. Our results highlight a critical role of cortical astroglia in the development of anhedonia and further support the idea of targeting astroglia for the treatment of depression.
Keyphrases
- stress induced
- prefrontal cortex
- single cell
- induced apoptosis
- traumatic brain injury
- cell therapy
- escherichia coli
- sleep quality
- poor prognosis
- signaling pathway
- cell cycle arrest
- sars cov
- oxidative stress
- binding protein
- drug induced
- stem cells
- mesenchymal stem cells
- cancer therapy
- diabetic rats
- endoplasmic reticulum stress
- pi k akt
- cell death
- small molecule