summary: Regulatory T cells (Tregs), normally tasked with regulating the immune system, may also play a pivotal role in stabilizing mood.
It is controlled by the transcription factor Foxp3, and a decrease in its expression has been linked to major depressive disorders. When Tregs were depleted in laboratory mice, they showed increased anxiety and depression behaviors, which were reversed when Foxp3-expressing cells were restored.
This points to a possible link between immune responses, mood disorders, and even cognitive impairments as seen in Alzheimer’s disease.
- Foxp3-controlled regulatory T cells (Tregs) may influence mood and cognitive function.
- Tregs depletion in mice led to behaviors indicating anxiety and depression.
- Cognitive impairments have been seen in Alzheimer’s disease models when Tregs are depleted, suggesting an immune response may be linked to memory problems.
source: PNAS Nexus
According to a study, regulatory T cells — the body’s immune system horses — may also stabilize mood.
Forkhead box P3 (Foxp3) is a transcription factor that controls the production of regulatory T cells (Tregs). Tregs are the main regulators of the adaptive immune system. However, previous research also indicates that Trigesic can affect mood. Decreased Foxp3 expression is associated with major depressive disorders.
Giulio Maria Pasinetti and colleagues tested a group of lab mice whose cells could be temporarily depleted in standard tasks designed to measure depression and anxiety in rodents.
Treg-depleted mice were more likely to hide in the dark, move less, and abandon self-preservation routines more easily—suggesting that Treg-depleted mice were more anxious and depressed than control mice.
These neurobehavioral changes were reversed in Treg-depleted mice after restoration of Foxp3-expressing cells, and the restored Treg mice were more similar to controls than to Treg-depleted mice.
In addition, mice that had been bred for an Alzheimer’s disease model showed cognitive impairment when their cells were depleted.
The researchers hypothesize that Treg depletion causes a proliferation of peripheral immune cells, some of which can cross the blood-brain barrier into the brain and trigger inflammatory responses in the hippocampal formation.
This transient activation of innate immunity in the brain can cause anxiety, depression, or Alzheimer’s-related cognitive decline, according to the authors.
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author: Giulio Maria Pacinetti
source: PNAS Nexus
communication: Giulio Maria Pasinetti – PNAS Nexus
picture: Image credited to Neuroscience News
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“Transient anxiety and depression-like behaviors are associated with depletion of Foxp3-expressing cells via the inflammasome in the brain.By Giulio Maria Pasinetti, et al. PNAS Nexus
Transient anxiety and depression-like behaviors are associated with depletion of Foxp3-expressing cells via the inflammasome in the brain.
Forkhead box P3 (Foxp3) is a transcription factor that affects the action of regulatory T cells (Tregs) that modulate the peripheral immune response.
Treg-mediated innate immunity and Treg-mediated adaptive immunity are receiving much attention for their influence on mechanisms associated with anxiety and depression.
Here we demonstrate that depletion of Foxp3-expressing cells causally enhances transient anxiety-like and depression-like behaviors associated with activation of inflammatory particles in ‘depleted regulatory T-cell’ (DEREG) mice.
We found that recovery of Foxp3-expressing cells causally reverses neurobehavioral changes through alteration of innate immune responses as assessed by caspase-1 activity and interleukin-1β (IL-1β) release in the hippocampus formation of DEREG mice.
Furthermore, we found that depletion of Foxp3-expressing cells leads to a significant elevation of granulocytes, monocytes, and macrophages in the blood, which correlates with transient expression of matrix metalloprotease-9.
Similarly, we found that depletion of Foxp3-expressing cells in 5xFAD, a mouse model of Alzheimer’s disease (AD), shows an elevated level of activated caspase-1, enhanced IL-1β secretion, and an increased level of amyloid-beta (Aβ).1-42 and Aβ plaque burden in hippocampal formation that coincided with an acceleration of cognitive decline at the presymptomatic age in 5xFAD mice.
Thus, our study provides evidence supporting the idea that Foxp3 may have a causal effect on peripheral immune responses. This, in turn, can enhance the innate immune response within the brain, which can lead to anxiety- and depression-like behaviors or cognitive decline.