The French National Centre for Scientific Research


Circadian clock, sleep and homeostatic plasticity in mood disorders

Team leader : Tsvetan Serchov


Mood disorders are among the most commonly diagnosed disabling mental diseases. Despite the numerous pathophysiological hypotheses, elucidating the neurobiological basis of depression remains one of the foremost challenges in modern psychiatry.

Disruptions of sleep and circadian rhythm are associated with the development of various psychiatric diseases. Chronotherapies, which include a variety of strategies that modulate biological clock and sleep-wake cycle, such as sleep deprivation and light therapy, are alternative treatments for mood and sleep disorders. We have recently shown that the rapid antidepressant effects of acute sleep deprivation depend on enhanced adenosinergic and glutamatergic signaling. However, the involvement of the circadian clock in the antidepressant action of different chronotherapies and the pathophysiology of mood disorders is not yet well understood.

Therefore our research aims are:

  1. To investigate how chronic stress, a major factor causing depression, influences molecular circadian clockwork in different limbic brain regions
  2. To test how direct modulation of the circadian clock genes affects mood and sleep regulation
  3. To characterize the crosstalk between circadian, sleep homeostatic mechanisms and glutamatergic signaling in the rapid antidepressant therapy
  4. To study the impact of adenosinergic signaling mediating the effects of sleep loss on mood.


Members

Principal investigator

Tsvetan Serchov
 
PostDoc

Wilf Gardner
 
MSc student

Carole Marchese
 
Funding

Fondation pour la Recherche Medical (FRM)
University of Strasbourg Institute for Advanced Studies (USIAS)
German Research Foundation (DFG)


Selected publications

Serchov T*, Schwarz I, Theiss A, Sun L, Holz A, Döbrössy MD, Schwarz MK, Normann C, Biber K, van Calker D. (2019) Enhanced adenosine A1 receptor and Homer1a expression in hippocampus modulates the resilience to stress-induced depression-like behavior. >Neuropharmacology. 107834. doi: 10.1016/j.neuropharm.2019.

Holz A, Mülsch F, Schwarz MK, Hollmann M, Döbrössy MD, Coenen VA, Bartos M, Normann C, Biber K, van Calker D, Serchov T*. (2019) Enhanced mGlu5 Signaling in Excitatory Neurons Promotes Rapid Antidepressant Effects via AMPA Receptor Activation. Neuron. pii: S0896-6273(19)30637-3. doi: 10.1016/j.neuron.2019.07.011.

van Calker D, Biber K, Domschke K, Serchov T*. (2019) The Role of Adenosine Receptors in Mood and Anxiety Disorders. J Neurochem. doi: 10.1111/jnc.14841.

van Calker D, Serchov T, Normann C, Biber K. (2018) Recent insights into antidepressant therapy: Distinct pathways and potential common mechanisms in the treatment of depressive syndromes. Neurosci Biobehav Rev. 88:63-72. doi:10.1016/j.neubiorev.2018.03.014.

Normann C, Frase S, Haug V, von Wolff G, Clark K, Münzer P, Dorner A, Scholliers J, Horn M, Vo Van T, Seifert G, Serchov T, Biber K, Nissen C, Klugbauer N, Bischofberger J. (2018) Antidepressants Rescue Stress-Induced Disruption of Synaptic Plasticity via Serotonin Transporter-Independent Inhibition of L-Type Calcium Channels. Biol Psychiatry. 84(1):55-64. doi: 10.1016/j.biopsych.2017.10.008.

Serchov T, Clement HW, Schwarz MK, Iasevoli F, Tosh DK, Idzko M, Jacobson KA, de Bartolomeis A, Normann C, Biber K, van Calker D. (2015) Increased Signaling via Adenosine A1 Receptors, Sleep Deprivation, Imipramine, and Ketamine Inhibit Depressive-like Behavior via Induction of Homer1a. Neuron. 87(3):549-62. doi: 10.1016/j.neuron.2015.07.010.

Serchov T, Jilg A, Wolf CT, Radtke I, Stehle JH, Heumann R. (2016) Ras Activity Oscillates in the Mouse Suprachiasmatic Nucleus and Modulates Circadian Clock Dynamics. Mol Neurobiol. 53(3):1843-1855. doi: 10.1007/s12035-015-9135-0.

 


 
The French National Centre for Scientific Research