What We Do
Professor Albert is working in the area of molecular mechanisms of autoreceptor desensitization. Successful therapy of major depression (as well as generalized anxiety, obsessive-compulsive, and other mental disorders) using a variety of antidepressant compounds (e.g., serotonin-specific reuptake inhibitors, monoamine oxidase inhibitors, tricyclic antidepressants, and 5-HT1A receptor agonists) is associated with a three-week time course before clinical improvement may be observed. Antidepressants appear to act by directly modifying the serotonin (5-HT) system which originates in the raphe nuclei of the brain. Desensitization of inhibitory serotonin-1A (5-HT1A) autoreceptors occurs following chronic (but not acute) antidepressant treatment, and allows for enhanced firing of serotonergic raphe neurons in the presence of antidepressant (Figure
below). The enhanced firing results in increased serotonergic neurotransmission, as the post-synaptic 5-HT receptors do not desensitize to the same extent. Receptor desensitization involves several sequential steps: uncoupling (min), mediated by phosphorylation, receptor sequestration (min-hr), and down-regulation (hr-days), involving receptor degradation and/or decreased receptor synthesis. Because of the chronic time course these disease and treatments, Professor Albert has focused on understanding transcriptional regulator of the 5-HT1A receptor gene.
The importance of transcriptional and post-transcriptional events in regulating the 5-HT system is being probed using 5-HT1A receptor promoter constructs with the ultimate aim of identifying genetic sequences that may confer susceptibility to mental disorders or responsiveness to anti-depressant treatment. The transcription factors that bind to these sites and their role in vivo in 5-HT activity and anxiety and depression behavior is being tested using global and conditional knockout and optogenetic mouse strategies. In addition the role of early and late life stress and DNA methylation in conferring stress-induced susceptibility is also being tested using mouse models.
Professor Albert has established research collaborations with the Royal Ottawa Hospital (Institute for Mental Health Research) to apply this work in the areas of depression, anxiety and schizophrenia. He is also a member of the Heart and Stroke Foundation Canadian Partnership for Stroke Recovery and the University of Ottawa Brain and Mind Research Institute.
Five Key Publications
Albert lab members in bold
Publications archived at: ResearchGate
1. Le François B, Soo J, Millar
AM, Daigle M
, Le Guisque AM, Leman S, Minier F,
Belzung C, Albert PR
. (2015) Chronic mild stress and antidepressant treatment
Neurobiol Disease, in press.
, Kotarska K, Misztak P, Rafalo
A, Daigle M,
Curzytek K, Kubera M, Basta-Kaim A, Nowak G, Albert PR
(2014) Stress-induced alterations in 5-HT1A receptor transcriptional modulators
NUDR and Freud-1. Int J Neuropsychopharm 17, 1763-75
3. Czesak M*, Le François B*, Millar AM, Deria M, Daigle M,
Visvader JE, Anisman H, Albert PR
Increased serotonin-1A (5-HT1A) autoreceptor expression and reduced
raphe serotonin levels in Deformed Epidermal Autoregulatory Factor-1
(Deaf-1) gene knock-out mice. J Biol Chem 287, 6615-6627.
4. Hadjighassem MR
, Szewczyk B
, Austin MC, Daigle M
, Stockmeier CA, Albert PR
(2009) Human Freud-2/CC2D1B: a novel repressor of post-synaptic 5-HT1A receptor expression. Biol Psychiatry 66, 214-222.
5. Lemonde S
, Turecki G, Bakish D, Du L, Hrdina PD, Bown CD
, Basak A, Kushwaha N
, Sequeira A, Morris SJ, Ou X, and Albert PR
Impaired repression at a 5-hydroxytryptamine 1A receptor polymorphism
associated with major depression and
suicide. J Neuroscience 23,
Meet the Albert Lab