Jay Gingrich, MD, PhD
Research Interest
The mouse represents the most tractable experimental model of vertebrate behavior and brain function currently available. We use genetic, pharmacologic, environmental, and other manipulations to probe mechanisms underlying normal and abnormal behaviors that have relevance to neuropsychiatry. Current projects examine the role of serotonin in brain development, the role of serotonin signaling in anxiety, depression, and psychosis; the epigenetics of complex disorders such as autism and schizophrenia, and the biological basis of environmental effects on genetic vulnerabilities to behavioral abnormalities. The mouse and the powerful techniques that can be applied to its study offer the capacity go beyond correlation and establish causality in our quest to understand how the brain affects behavior.
Talati A, Guffanti G, Odgerel Z, Ionita-Laza I, Malm H, Sourander A, Brown AS, Wickramaratne PJ, Gingrich JA, Weissman MM. (2015). Genetic variants within the serotonin transporter associated with familial risk for major depression. Psychiatry Res. 228:170-173. doi: 10.1016/j.psychres.2015.04.015.
Rebello TJ, Yu Q, Goodfellow NM, Caffrey Cagliostro MK, Teissier A, Morelli E, Demireva EY, Chemiakine A, Rosoklija GB, Dwork AJ, Lambe EK, Gingrich JA, Ansorge MS. (2014). Postnatal day 2 to 11 constitutes a 5-HT-sensitive period impacting adult mPFC function. J Neurosci. 34:12379-12393. doi: 10.1523/JNEUROSCI.1020-13.2014.
Milekic MH, Xin Y, O'Donnell A, Kumar KK, Bradley-Moore M, Malaspina D, Moore H, Brunner D, Ge Y, Edwards J, Paul S, Haghighi FG, Gingrich JA. (2014). Age-related sperm DNA methylation changes are transmitted to offspring and associated with abnormal behavior and dysregulated gene expression. Mol Psychiatry. doi: 10.1038/mp.2014.84.
Yu Q, Teixeira CM, Mahadevia D, Huang YY, Balsam D, Mann JJ, Gingrich JA, Ansorge MS. (2014). Optogenetic stimulation of DAergic VTA neurons increases aggression.
Mol Psychiatry. 19:635. doi: 10.1038/mp.2014.45. No abstract available.
Goodfellow NM, Sargin D, Ansorge MS, Gingrich JA, Lambe EK. (2014). Mice with compromised 5-HTT function lack phosphotyrosine-mediated inhibitory control over prefrontal 5-HT responses. J Neurosci. 34:6107-6111. doi: 10.1523/JNEUROSCI.3762-13.
Yu Q, Teixeira CM, Mahadevia D, Huang Y, Balsam D, Mann JJ, Gingrich JA, Ansorge MS. (2014). Dopamine and serotonin signaling during two sensitive developmental periods differentially impact adult aggressive and affective behaviors in mice. Mol Psychiatry19:688-98. doi: 10.1038/mp.2014.10. Epub 2014 Mar 4.
McOmish CE, Lira A, Hanks JB, Gingrich JA. (2012). Clozapine-induced locomotor suppression is mediated by 5-HT2A receptors in the forebrain.Neuropsychopharmacology. 37:2747-2755. doi: 10.1038/npp.2012.139. Epub 2012.
Morelli E, Moore H, Rebello TJ, Gray N, Steele K, Esposito E, Gingrich JA, Ansorge MS. Chronic 5-HT transporter blockade reduces DA signaling to elicit basal ganglia dysfunction. J Neurosci. 2011 Nov 2;31(44):15742-50. doi: 10.1523/JNEUROSCI.2989-11.2011.
Xin Y, O'Donnell AH, Ge Y, Chanrion B, Milekic M, Rosoklija G, Stankov A, Arango V, Dwork AJ, Gingrich JA, Haghighi FG. (2011). Role of CpG context and content in evolutionary signatures of brain DNA methylation. Epigenetics. 6:1308-18. doi: 10.4161/epi.6.11.17876. Epub 2011.
McOmish CE, Gingrich JA. (2011). Stress and the baby brain. Biol Psychiatry. 70:1006-7. doi: 10.1016/j.biopsych. No abstract available.
Muller JM, Morelli E, Ansorge M, Gingrich JA. (2010). Serotonin transporter deficient mice are vulnerable to escape deficits following inescapable shocks. Genes Brain Behav.10:166-175. doi: 10.1111/j.1601-183X.2010.00652.x. Epub 2010.
Edwards JR, O'Donnell AH, Rollins RA, Peckham HE, Lee C, Milekic MH, Chanrion B, Fu Y, Su T, Hibshoosh H, Gingrich JA, Haghighi F, Nutter R, Bestor TH. (2010). Chromatin and sequence features that define the fine and gross structure of genomic methylation patterns.
Genome Res. 20:972-980. doi: 10.1101/gr.101535.109.
Bortolozzi A, Masana M, Díaz-Mataix L, Cortés R, Scorza MC, Gingrich JA, Toth M, Artigas F. (2010). Dopamine release induced by atypical antipsychotics in prefrontal cortex requires 5-HT(1A) receptors but not 5-HT(2A) receptors. Int J Neuropsychopharmacol. 13:1299-1314. doi: 10.1017/S146114571000009X.
Oberlander TF, Gingrich JA, Ansorge MS. (2009). Sustained neurobehavioral effects of exposure to SSRI antidepressants during development: molecular to clinical evidence.
Clin Pharmacol Ther. 86:672-677. doi: 10.1038/clpt.2009.201.
Yadav VK, Oury F, Suda N, Liu ZW, Gao XB, Confavreux C, Klemenhagen KC, Tanaka KF, Gingrich JA, Guo XE, Tecott LH, Mann JJ, Hen R, Horvath TL, Karsenty G. (2009). A serotonin-dependent mechanism explains the leptin regulation of bone mass, appetite, and energy expenditure. Cell. 138:976-989. doi: 10.1016/j.cell.2009.06.051.
Halberstadt AL, van der Heijden I, Ruderman MA, Risbrough VB, Gingrich JA, Geyer MA, Powell SB. (2009). 5-HT(2A) and 5-HT(2C) receptors exert opposing effects on locomotor activity in mice. Neuropsychopharmacology. 34:1958-1967. doi: 10.1038/npp.2009.29.
Yadav VK, Ryu JH, Suda N, Tanaka KF, Gingrich JA, Schütz G, Glorieux FH, Chiang CY, Zajac JD, Insogna KL, Mann JJ, Hen R, Ducy P, Karsenty G. (2008). Lrp5 controls bone formation by inhibiting serotonin synthesis in the duodenum. Cell. 135:825-837. doi: 10.1016/j.
Shanahan NA, Holick Pierz KA, Masten VL, Waeber C, Ansorge M, Gingrich JA, Geyer MA, Hen R, Dulawa SC. Chronic reductions in serotonin transporter function prevent 5-HT1B-induced behavioral effects in mice. Biol Psychiatry. 2009 Mar 1;65(5):401-8. doi: 10.1016/j.biopsych.2008.09.026.
Lu R, Alioua A, Kumar Y, Kundu P, Eghbali M, Weisstaub NV, Gingrich JA, Stefani E, Toro L. (2008). c-Src tyrosine kinase, a critical component for 5-HT2A receptor-mediated contraction in rat aorta. J Physiol. 586:3855-3869. doi: 10.1113/jphysiol.
Chen YJ, Johnson MA, Lieberman MD, Goodchild RE, Schobel S, Lewandowski N, Rosoklija G, Liu RC, Gingrich JA, Small S, Moore H, Dwork AJ, Talmage DA, Role LW. (2008). Type III neuregulin-1 is required for normal sensorimotor gating, memory-related behaviors, and corticostriatal circuit components. J Neurosci. 28:6872-6883. doi: 10.1523/JNEUROSCI.1815-08.2008.
González-Maeso J, Ang RL, Yuen T, Chan P, Weisstaub NV, López-Giménez JF, Zhou M, Okawa Y, Callado LF, Milligan G, Gingrich JA, Filizola M, Meana JJ, Sealfon SC. (2008). Identification of a serotonin/glutamate receptor complex implicated in psychosis. Nature. 452:93-97. doi: 10.1038/nature06612.
Ansorge MS, Morelli E, Gingrich JA. (2008). Inhibition of serotonin but not norepinephrine transport during development produces delayed, persistent perturbations of emotional behaviors in mice. J Neurosci. 2008 Jan 2;28(1):199-207. doi: 10.1523/JNEUROSCI.3973-07.2008.
Van Steenwinckel J, Brisorgueil MJ, Fischer J, Vergé D, Gingrich JA, Bourgoin S, Hamon M, Bernard R, Conrath M. (2008). Role of spinal serotonin 5-HT2A receptor in 2',3'-dideoxycytidine-induced neuropathic pain in the rat and the mouse. Pain. 137:66-80.
Béïque JC, Imad M, Mladenovic L, Gingrich JA, Andrade R. (2007). Mechanism of the 5-hydroxytryptamine 2A receptor-mediated facilitation of synaptic activity in prefrontal cortex.
Proc Natl Acad Sci USA. 104:9870-9875.
Gonzalez-MaesoJ, Weisstaub NV, Zhou M, Chan P, Ivic L, Ang R, Lira A, Bradley-MooreM, Ge Y, Zhou Q, Sealfon SC, Gingrich JA (2007). Hallucinogens recruitspecific cortical 5-HT(2A) receptor-mediated signaling pathways toaffect behavior. Neuron, 53: 439-452.
Ansorge MS, Hen R, Gingrich JA (2007). Neurodevelopmental origins of depressive disorders Curr. Opin. Pharmacol., 7: 8-17.
WeisstaubNV, Zhou M, Lira A, Lambe E, González-Maeso J, Hornung JP, Sibille E,Underwood M, Itohara S, Dauer WT, Ansorge MS, Morelli E, Mann JJ, TothM, Aghajanian G, Sealfon SC, Hen R, Gingrich JA (2006). Cortical 5-HT2Areceptor signaling modulates anxiety-like behaviors in mice. Science, 313: 536-540.
Gingrich JA (2005). Oxidative stress is the new stress. Nat. Med. 11: 1281-1282.
Ansorge M, Zhou M, Lira A, Hen R, Gingrich JA (2004). Early life blockade of the 5-HT transporter alters emotionalbehavior in adult mice. Science, 306: 879-881.
Gonzalez-MaesoJ, Yuen T, Ebersole BJ, Wurmback E., Lira A., Zhou M., Weisstaub N.,Hen R, Gingrich JA, Sealfon SC (2003). Transcriptome fingerprintsdistinguish hallucinogenic and nonhallucinogenic 5-hydroxytryptamine 2Areceptor agonist effects in mouse somatosensory cortex. J. Neurosci., 23: 8836-8843.
Lira A, Zhou M, Castanon N, Ansorge M S, Gordon J A, Francis J H,Bradley-Moore M, Lira J, Underwood M D, Arango V, Hofer MA, Hen R,Gingrich JA. (2003). Altered depression-related behaviors andfunctional changes in the dorsal raphe nucleus of serotonintransporter-deficient mice. Biol. Psych., 54: 960-971.
- Treatment of Psychiatric Disorders in Pregnancy
- Depression, Anxiety, Schizophrenia
- Treatment Resistance
- Cognitive/Systems Neuroscience
- Neurogenetics
- Models of Psychiatric Disorders