The intersection of astrocytes and the endocannabinoid system in the lateral habenula: on the fast-track to novel rapid-acting antidepressants

TY - JOUR

T1 - The intersection of astrocytes and the endocannabinoid system in the lateral habenula

T2 - on the fast-track to novel rapid-acting antidepressants

AU - Arjmand, Shokouh

AU - Landau, Anne M

AU - Varastehmoradi, Bardia

AU - Andreatini, Roberto

AU - Joca, Sâmia

AU - Wegener, Gregers

PY - 2022/8

Y1 - 2022/8

N2 - Despite attaining significant advances toward better management of depressive disorders, we are still facing several setbacks. Developing rapid-acting antidepressants with sustained effects is an aspiration that requires thinking anew to explore possible novel targets. Recently, the lateral habenula (LHb), the brain's "anti-reward system", has been shown to go awry in depression in terms of various molecular and electrophysiological signatures. Some of the presumed contributors to such observed aberrations are astrocytes. These star-shaped cells of the brain can alter the firing pattern of the LHb, which keeps the activity of the midbrain's aminergic centers under tight control. Astrocytes are also integral parts of the tripartite synapses, and can therefore modulate synaptic plasticity and leave long-lasting changes in the brain. On the other hand, it was discovered that astrocytes express cannabinoid type 1 receptors (CB 1R), which can also take part in long-term plasticity. Herein, we recount how the LHb of a depressed brain deviates from the "normal" one from a molecular perspective. We then try to touch upon the alterations of the endocannabinoid system in the LHb, and cast the idea that modulation of astroglial CB 1R may help regulate habenular neuronal activity and synaptogenesis, thereby acting as a new pharmacological tool for regulation of mood and amelioration of depressive symptoms.

AB - Despite attaining significant advances toward better management of depressive disorders, we are still facing several setbacks. Developing rapid-acting antidepressants with sustained effects is an aspiration that requires thinking anew to explore possible novel targets. Recently, the lateral habenula (LHb), the brain's "anti-reward system", has been shown to go awry in depression in terms of various molecular and electrophysiological signatures. Some of the presumed contributors to such observed aberrations are astrocytes. These star-shaped cells of the brain can alter the firing pattern of the LHb, which keeps the activity of the midbrain's aminergic centers under tight control. Astrocytes are also integral parts of the tripartite synapses, and can therefore modulate synaptic plasticity and leave long-lasting changes in the brain. On the other hand, it was discovered that astrocytes express cannabinoid type 1 receptors (CB 1R), which can also take part in long-term plasticity. Herein, we recount how the LHb of a depressed brain deviates from the "normal" one from a molecular perspective. We then try to touch upon the alterations of the endocannabinoid system in the LHb, and cast the idea that modulation of astroglial CB 1R may help regulate habenular neuronal activity and synaptogenesis, thereby acting as a new pharmacological tool for regulation of mood and amelioration of depressive symptoms.

KW - Antidepressive Agents/pharmacology

KW - Astrocytes

KW - Endocannabinoids/pharmacology

KW - Habenula

KW - Synapses/physiology

UR - http://www.scopus.com/inward/record.url?scp=85130242716&partnerID=8YFLogxK

U2 - 10.1038/s41380-022-01598-4

DO - 10.1038/s41380-022-01598-4

M3 - Review

C2 - 35585261

SN - 1359-4184

VL - 27

SP - 3138

EP - 3149

JO - Molecular Psychiatry

JF - Molecular Psychiatry

IS - 8

ER -