Albert Lab

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Contact Information

Paul Albert, PhD

OHRI (Neuroscience)
451 Smyth Road
Ottawa, ON K1H-8M5

What We Do

Successful therapy of major depression and anxiety with antidepressant compounds (e.g., serotonin-specific reuptake inhibitors, SSRIs) directly enhances the serotonin (5-HT) system, which originates in the raphe nuclei of the brain.  However, desensitization of inhibitory serotonin-1A (5-HT1A) autoreceptors is required for SSRI response, and allows for enhanced firing of 5-HT neurons to increase 5-HT.  Because of the chronic time course the disease and its treatment, we have focused on understanding transcriptional regulation of the 5-HT1A receptor gene.  We have identified a genetic variant (GG-1019) that leads to increased 5-HT1A autoreceptors and reduced post-synaptic 5-HT1A receptors, and is associated with increase risk for depression and suicide, and resistance to SSRIs (Figure below).

To address the molecular events that impact chronic depression, we examine the mechanisms of functional promoter polymorphisms, like the GG-1019 5-HT1A change, and of chronic stress-induced epigenetic modifications on gene expression, behavior, and antidepressant response in human and mouse models of mental illness.  Our fundamental research has identified the molecular mechanisms that regulate key genes in the serotonin (5-HT) and dopamine systems, including the 5-HT1A and dopamine-D2 receptor genes and the TPH2 gene.  We have identified key DNA elements that regulate 5-HT1A receptor expression, cloned the novel regulators that target these elements, and identified and characterized the GG-1019 gene polymorphism that affects this regulation in cell and mouse models and in humans. For several years we have examined changes in mental illness of RNA and protein expression of the 5-HT1A receptor and its key transcriptional regulators that we have identified, including Freud-1, Freud-2 and Deaf1.  In addition, we have recently examined the DNA methylation patterns of the 5-HT1A promoter sites, and upstream sites recognized by these transcription factors. We have identified novel regulators of these transcription factors, identified risk polymorphisms in post-stroke depression and established a new mouse model of post-stroke depression.  We have also developed a number of mouse conditional knockout models the address the function of transcription factors in serotonin regulation and depression/anxiety phenotypes.  We have begun to analyze mice for optogenetic analysis to directly assess the role of serotonin activity in depression and anxiety.   

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.

Selected Publications

Five Key Publications

Albert lab members in bold
Publications archived at: ResearchGate
Publications available at: PubMed Central Canada

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 alter 5-HT1A receptor expression by modifying DNA methylation of a conserved Sp4 site.  Neurobiol Dis 82: 332-41.

2. Szewczyk B, 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 (2012) 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 (2003) Impaired repression at a 5-hydroxytryptamine 1A receptor polymorphism associated with major depression and suicide. J Neuroscience 23, 8788-8799.

Meet the Albert Lab