Targeting the CCL2-CCR2 axis in depressive disorders.

Area of Science:

• Neuroscience
• Immunology
• Psychiatry

Background:

• Affective disorders involve immune system malfunction and proinflammatory mediators.
• Chemokines, like CCL2 and its receptor CCR2, are implicated in brain diseases and abnormal brain-immune dialogue in depression.

Purpose of the Study:

• To review the role of the CCL2-CCR2 axis in the central nervous system under physiological and pathological conditions.
• To explore the contribution of the CCL2-CCR2 system to affective disorders.
• To highlight the CCL2-CCR2 pathway as a potential pharmacological target for depression.

Main Methods:

• Literature review of studies on CCL2-CCR2 axis in CNS.
• Analysis of the pathway's involvement in neurobiological processes (neurogenesis, neurotransmission, neuroinflammation, neurodegeneration, neuroregeneration).
• Examination of the pathway's role in affective disorders and potential as a therapeutic target.

Main Results:

• The CCL2-CCR2 axis influences various neurobiological processes, including neuroinflammation and neurodegeneration.
• Initially considered proinflammatory, CCL2-CCR2's role in depression may stem from impaired homeostatic functions.
• Dysfunctions in the CCL2-CCR2 dyad are linked to nervous system malfunctions in affective disorders.

Conclusions:

• The CCL2-CCR2 axis plays a complex role in the central nervous system, impacting both physiological and pathological states.
• Impaired homeostasis of the CCL2-CCR2 system, rather than solely inflammation, is associated with depression.
• The CCL2-CCR2 pathway represents a promising target for developing novel antidepressant therapies.