Molecular Neuropsychopharmacology
Description
Integrated genetic and epigenetic approach to developmental psychiatric disorders: analysis of human blood and brain.
Environmental stimuli influence the developmental trajectories of neural circuits from birth through adolescence. Exposure to harmful environmental stimuli during development may result in increased vulnerability to psychiatric disorders. These effects may be mediated through epigenetic mechanisms. We conduct epigenome-wide analysis of DNA methylation in blood and brain samples collected at different developmental stages and from alcohol dependent subjects. Loci associated with phenotypic traits are considered as candidate biomarkers for alcohol dependence. Mechanisms underlying these associations are in focus as putative therapeutic targets for the treatment of alcohol dependence
Pathogenic mechanisms of human neuropeptide mutations
Much of our knowledge about functions of genes in human brain has come from analysis of human mutations. Such mutations represent entry points into novel signaling pathways and molecular mechanisms. We have identified missense mutations in the human prodynorphin gene (PDYN) coding for a precursor to opioid peptides dynorphins. These mutations cause profound neurodegeneration in the brain underlying the development of subtype of spinocerebellar ataxia, a dominantly inherited neurodegenerative disorder. Remarkably, seven out of eight mutations are located in dynorphins, which also have non-opioid neurodegenerative activities. This is the first finding on neuropeptide mutations underlying human neuropathology. The best-established function of the dynorphins in the brain is regulation of the anti-reward system by inducing dysphoria that counterbalances positive hedonic effects of endorphins and enkephalins, and addictive substances. Analysis of PDYN mutations could uncover novel mechanisms of anti-reward - reward regulation that are generally unknown.
Selected publications
Bazov I et al. Molecular Neurobiology doi: 10.1007/s12035-017-0844-4..
Bazov I Translational Psychiatry In PRESS.
Bazov I et al. Cerebral Cortex doi: 10.1093/cercor/bhx181.
Sarkisyan D et al. Acta Neuropathol. 2017 133, 485-87.
Kononenko O et al. FASEB J. 2017 31, 1953-1963.
Kononenko O et al. Biochim Biophys Acta 2017 1861, 246-255.
Watanabe H et al. Cerebral Cortex 2015 25, 97-108.
Smeets CJ et al. Brain 2015 138, 2537-52.
Ruggeri B et al. Am. J Psych. 2015 172, 543-52.
Maximyuk O et al. Cell Death Dis. 2015 2;6:e1683.
Henriksson R et al. Biochim Biophys Acta 2014 1839, 1226-32.
Kuzmin A et al. Translational Psychiatry 2013 Oct 8;3:e310.
Dong L et al. Am. J. Psychiatry 2011, 168, 1090-98.
Schumann G et al. Proc. Natl. Acad. Sci. USA. 2011 108, 7119-24.
Yakovleva T et al. Brain Behav. Immun. 2011, Suppl 1, S29-38.
Bakalkin G et al. Am. J. Hum. Genet. 2010 87, 593-03.
Publications
Inhibition of Insulin-Regulated Aminopeptidase by Imidazo[1,5-α]pyridines; Synthesis and Evaluation
Part of International Journal of Molecular Sciences, 2024
Part of Hormones and Behavior, 2024
- DOI for The decanoate esters of nandrolone, testosterone, and trenbolone induce steroid specific memory impairment and somatic effects in the male rat
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Part of International Journal of Molecular Sciences, 2024
N-(Heteroaryl)thiophene sulfonamides as angiotensin AT2 receptor ligands
Part of European Journal of Medicinal Chemistry, 2024
DNA methylation at DLGAP2 and risk for relapse in alcohol dependence during acamprosate treatment
Part of Drug And Alcohol Dependence, 2024
Biological aging markers in blood and brain tissue indicate age acceleration in alcohol use disorder
Part of ALCOHOL-CLINICAL AND EXPERIMENTAL RESEARCH, p. 250-259, 2024
Part of Behavioural Brain Research, 2022
- DOI for Nandrolone decanoate and testosterone undecanoate differently affect stress hormones, neurotransmitter systems, and general activity in the male rat
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Part of Current Issues in Molecular Biology, p. 5000-5012, 2022
Part of Neural Regeneration Research, p. 2431-2433, 2022
2-Alkyl substituted benzimidazoles as a new class of selective AT2 receptor ligands
Part of Bioorganic & Medicinal Chemistry, 2022
Angiotensin II AT2 receptor ligands with phenylthiazole scaffolds
Part of Bioorganic & Medicinal Chemistry, 2022
Multi-omics signatures of alcohol use disorder in the dorsal and ventral striatum
Part of Translational Psychiatry, 2022
Part of eNeuro, 2021
Part of Journal of Steroid Biochemistry and Molecular Biology, 2021
- DOI for Structurally different anabolic androgenic steroids reduce neurite outgrowth and neuronal viability in primary rat cortical cell cultures
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Assessing Cell Viability Effects of Opioids in Primary Cortical Cells from Rat.
Part of Methods in Molecular Biology, p. 171-180, 2021
Part of eLIFE, 2021
The effects of morphine, methadone, and fentanyl on mitochondria: A live cell imaging study
Part of Brain Research Bulletin, p. 126-134, 2021
Part of Frontiers in Genetics, 2021
Part of Experimental Brain Research, p. 2221-2232, 2021
Part of European Journal of Neuroscience, p. 5560-5573, 2021
- DOI for Coordinated expression of the renin-angiotensin genes in the lumbar spinal cord: Lateralization and effects of unilateral brain injury
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Unilateral brain injury to pregnant rats induces asymmetric neurological deficits in the offspring
Part of European Journal of Neuroscience, p. 3621-3633, 2021
Part of Journal of Neurotrauma, p. 1679-1688, 2021
N-(Methyloxycarbonyl)thiophene sulfonamides as high affinity AT2 receptor ligands
Part of Bioorganic & Medicinal Chemistry, 2021
Part of European Journal of Pharmacology, 2021
Part of Molecular Psychiatry, p. 3884-3895, 2021
- DOI for Epigenome-wide meta-analysis of blood DNA methylation and its association with subcortical volumes: findings from the ENIGMA Epigenetics Working Group
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Genotype-dependent epigenetic regulation of DLGAP2 in alcohol use and dependence
Part of Molecular Psychiatry, p. 4367-4382, 2021
Part of European Journal of Pharmacology, 2020
- DOI for Direct stimulation of angiotensin II type 2 receptor reduces nitric oxide production in lipopolysaccharide treated mouse macrophages
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Part of Metabolomics, 2020
- DOI for Anabolic androgenic steroids exert a selective remodeling of the plasma lipidome that mirrors the decrease of the de novo lipogenesis in the liver
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Growth hormone increases dendritic spine density in primary hippocampal cell cultures
Part of Growth Hormone & IGF Research, p. 42-47, 2020
Part of ChemistryOpen, p. 325-337, 2020
Macrocyclic Peptidomimetics as Inhibitors of Insulin-Regulated Aminopeptidase (IRAP)
Part of RSC Medicinal chemistry, p. 234-244, 2020
Growing knowledge: How growth hormone improves learning
Part of Acta Physiologica, 2020
Part of Biomolecules, 2020
Part of Journal of Neurochemistry, p. 485-494, 2020
Hindlimb motor responses to unilateral brain injury: spinal cord encoding and left-right asymmetry
Part of Brain Communications, 2020
Part of Brain Communications, 2020
Part of ACS Medicinal Chemistry Letters, p. 1429-1434, 2020
Correlations between sex-related hormones, alcohol dependence and alcohol craving
Part of Drug And Alcohol Dependence, p. 183-190, 2019
Allele-Specific Methylation of SPDEF: A Novel Moderator of Psychosocial Stress and Substance Abuse
Part of American Journal of Psychiatry, p. 146-155, 2019
Focal traumatic brain injury induces neuroplastic molecular responses in lumbar spinal cord
Part of Restorative Neurology and Neuroscience, p. 87-96, 2019
Part of Cerebral Cortex, p. 1736-1751, 2019
High affinity rigidified AT(2) receptor ligands with indane scaffolds
Part of MedChemComm, p. 2146-2160, 2019
Part of Brain Research, p. 182-189, 2019
Toxic Impact of Anabolic Androgenic Steroids in Primary Rat Cortical Cell Cultures
Part of Neuroscience, p. 172-183, 2019
Part of ChemistryOpen, p. 114-125, 2019
Dynorphin and κ-Opioid Receptor Dysregulation in the Dopaminergic Reward System of Human Alcoholics.
Part of Molecular Neurobiology, p. 7049-7061, 2018
Differential effects of left and right neuropathy on opioid gene expression in lumbar spinal cord
Part of Brain Research, p. 78-83, 2018
Part of Journal of Neurotrauma, 2018
Part of Journal of Neurotrauma, 2018
Part of Journal of Neurotrauma, 2018