UCLA Neuroscience Program Ph.D. Admissions Neuroscience Faculty UCLA and Beyond  



Paul Micevych
Reproductive Neuroendocrinology, Neuroprotection, Pain

Work Email Address:  pmicevych@mednet.ucla.edu
Home Page: http://neurobionet.neurobio.ucla.edu/~micevych/

Work Address:
CHS
CHS
Phone Numbers:
(310)206-2162 Laboratory
310-206-0533 Laboratory II
310-206-8265 Office

Selected Publications:

Micevych P, Sinchak K. Estradiol regulation of progesterone synthesis in the brain.. Mol Cell Endocrinol. 2008; 290(1-2): 44-50.
Quesada A, Micevych P. Estrogen and progesterone modulate [35S] GTPgammaS binding to nociceptin receptors.. Neuroendocrinology 2008; 88(1): 35-42.
Li J, Micevych P, McDonald J, Rapkin A, Chaban V. Inflammation in the uterus induces phosphorylated extracellular signal-regulated kinase and substance P immunoreactivity in dorsal root ganglia neurons innervating both uterus and colon in rats.. J Neurosci Res. 2008; 86(12): 2746-52.
Micevych PE, Mermelstein PG. Membrane estrogen receptors acting through metabotropic glutamate receptors: an emerging mechanism of estrogen action in brain.. Mol Neurobiol. 2008; 38(1): 66-77.
Quesada A, Lee BY, Micevych PE. PI3 kinase/Akt activation mediates estrogen and IGF-1 nigral DA neuronal neuroprotection against a unilateral rat model of Parkinson's disease.. Dev Neurobiol. 2008; 68(5): 632-44.
Dewing P, Christensen A, Bondar G, Micevych P. PKC signaling in the hypothalamic arcuate nucleus regulates sexual receptivity in female rats.. Endocrinology 2008; .
Quesada A, Romeo HE, Micevych P. Distribution and localization patterns of estrogen receptor-beta and insulin-like growth factor- 1 receptors in neurons and glial cells of the female rat substantia nigra: localization of ERbeta and IGF-1R in substantia nigra.. J Comp Neurol 2007; 503(1): 198-208.
Dewing P, Boulware MI, Sinchak K, Christensen A, Mermelstein PG, Micevych P. Membrane estrogen receptor-alpha interactions with metabotropic glutamate receptors 1a modulate female sexual receptivity in rats.. J Neurosci. 2007; 27(35): 9294-300.
Poulsen DJ, Standing D, Bullshields K, Spencer K, Micevych PE, Babcock AM. Overexpression of hippocampal Ca2+/calmodulin-dependent protein kinase II improves spatial memory.. J Neurosci Res 2007; 85(4): 735-9.
Sinchak K, Dewing P, Cook M, Micevych P. Release of orphanin FQ/nociceptin in the medial preoptic nucleus and ventromedial nucleus of the hypothalmus facilitates lordosis.. Horm Behav 2007; 51(3): 406-12.
Chaban V, Christensen A, Wakamatsu M, McDonald M, Rapkin A, McDonald J, Micevych P. The same dorsal root ganglion neurons innervate uterus and colon in the rat.. Neuroreport 2007; 18(3): 209-12.
Dewing P, Chiang CW, Sinchak K, Sim H, Fernagut PO, Kelly S, Chesselet MF, Micevych PE, Albrecht KH, Harley VR, Vilain E> Direct regulation of adult brain function by the male-specific factor SRY.. Curr Biol 2006; 16(4): 415-20.
Micevych PE, Chaban V, Ogi J, Dewing P, Lu JK, Sinchak K. Estradiol stimulates progesterone synthesis in hypothalamic astrocyte cultures.. Endocrinology 2006; 148(2): 782-9.
Quesada A, Micevych P. Estrogen and CCK1 receptor modification of mu-opioid receptor binding in the cortex of female rats.. Brain Res 2006; 1073-1074: 316-20.
Sinchak K, Romeo HE, Micevych PE. Site-specific estrogen and progestin regulation of orphanin FQ/nociceptin and nociceptin opioid receptor mRNA expression in the female rat limbic hypothalamic system.. J Comp Neurol 2006; 496(2): 252-68.
Chaban VV, Micevych PE. Estrogen receptor-alpha mediates estradiol attenuation of ATP-induced Ca2+ signaling in mouse dorsal root ganglion neurons.. J Neurosci Res 2005; 81(1): 31-7.
Soma KK, Sinchak K, Lakhter A, Schlinger BA, Micevych PE. Neurosteroids and female reproduction: estrogen increases 3beta-HSD mRNA and activity in rat hypothalamus.. Endocrinology 2005; 146(10): 4386-90.
Sinchak K, Shahedi K, Dewing P, Micevych P. Sexual receptivity is reduced in the female mu-opioid receptor knockout mouse.. Neuroreport 2005; 16(15): 1697-700.
Chaban VV, Lakhter AJ, Micevych P. A membrane estrogen receptor mediates intracellular calcium release in astrocytes.. Endocrinology 2004; 145(8): 3788-95.
Quesada A, Micevych PE. Estrogen interacts with the IGF-1 system to protect nigrostriatal dopamine and maintain motoric behavior after 6-hydroxdopamine lesions.. J Neurosci Res 2004; 75(1): 107-16.
Mills RH, Sohn RK, Micevych PE. Estrogen-induced mu-opioid receptor internalization in the medial preoptic nucleus is mediated via neuropeptide Y-Y1 receptor activation in the arcuate nucleus of female rats.. J Neurosci 2004; 24(4): 947-55.
Sinchak K, Mills RH, Eckersell CB, Micevych PE. Medial preoptic area delta-opioid receptors inhibit lordosis.. Behav Brain Res 2004; 155(2): 301-6.
Saldanha CJ, Schlinger BA, Micevych PE, Horvath TL. Presynaptic N-methyl-D-aspartate receptor expression is increased by estrogen in an aromatase-rich area of the songbird hippocampus.. J Comp Neurol 2004; 469(4): 522-34.
Chaban VV, Mayer EA, Ennes HS, Micevych PE. Estradiol inhibits atp-induced intracellular calcium concentration increase in dorsal root ganglia neurons.. Neuroscience 2003; 118(4): 941-8.
Sinchak K, Mills RH, Tao l, LaPolt P, Lu JK, Micevych PE Estrogen induces de novo progesterone synthesis in astrocytes.. Dev Neurosci 2003; 25(5): 343-8.
Micevych PE, Rissman EF, Gustafsson JA, Sinchak K. Estrogen receptor-alpha is required for estrogen-induced mu-opioid receptor internalization.. J Neurosci Res 2003; 71(6): 802-10.
Micevych P, Sinchak K, Mills RH, Tao L, LaPolt P, Lu JK. The luteinizing hormone surge is preceded by an estrogen-induced increase of hypothalamic progesterone in ovariectomized and adrenalectomized rats.. Neuroendocrinology 2003; 78(1): 29-35.
Sinchak K, Micevych P. Visualizing activation of opioid circuits by internalization of G protein-coupled receptors.. Mol Neurobiol 2003; 27(2): 197-222.
Cristobol R, Popper R, Lopez I, Micevych P, de Vellis J, Honrubia V. In vivo and in vitro localization of brain-derived neurotrophic factor, fibroblast growth factor-2 and their receptors in the bullfrog vestibular end organs.. Braih Res Mol Brain Res 2002; 102(1-2): 83-99.
Micevych P, Chaban V, Quesada A, Sinchak K. Oestrogen modulates cholecystokinin: opioid interactions in the nervous system.. Pharmacol Toxicol 2002; 91(6): 387-97.
Mills RH, Romeo HE, Lu JK, Micevych PE. Site-specific decrease of progesterone receptor mRNA expression in the hypothalamus of middle-aged persistently estrus rats.. Brain Res. 2002; 955(1-2): 200-6.
Raji-Kubba J, Micevych PE, Simmons DD. The superior olivary complex of the hamster has multiple periods of cholinergic neuron development.. J Chem Neuroanat 2002; 24(2): 75-93.
Tiwari-Woodruff SK, Buznikov AG, Vu TQ, Micevych PE, Chen K, Kornblum HI, Bronstein JM OSP/claudin-11 forms a complex with a novel member of the tetraspanin super family and beta1 integrin and regulates proliferation and migration of oligodendrocytes.. J Cell Biol 2001; 153(2): 295-305.
Sinchak, K Eckersell, C Quezada, V Norell, A Micevych, P Preproenkephalin mRNA levels are regulated by acute stress and estrogen stimulation.. Physiology & behavior. . 2000; 69(4-5): 425-32.
Nansen, EA Jokel, ES Lobo, MK Micevych, PE Ariano, MA Levine, MS Striatal ionotropic glutamate receptor ontogeny in the rat.. Developmental neuroscience. . 2000; 22(4): 329-40.
Lopez, I., Honrubia,V., Lee, S.-C., Chung, W.-H., Li, G., Beykirch, K., and Micevych, P. The protective effect of Brain-derived neurotrophic factor after gentomicin ototoxicity.. Am. J. Otology 1999; 20: 317-324.
Holland, K., Abelson, L. P and Micevych, P.E Ontogeny and estrogen regulation of prepubertal CCK and preproenkephalin mRNA in the hypothalamus and limbic system.. J. Comp. Neurol. 1998; 392: 48 - 57.
Holland, K. Popper, P. and Micevych, P.E Infusions of CCKA receptor mRNA antisense oligodeoxynucleotides inhibit lordosis behavior.. Physiol. and Behav. 1997; 62: (537- 543).
Eckersell C. and Micevych, P.E Opiate receptors modulate estrogen-induced cholecystokinin and trachykinin but not enkephalin mRNA levels in the limbic system and hypothalamus.. Neuroscience 1997; 80: (473-485).
Sinchak, K., D. Hendricks, R. Baroudi, and P. E Micevych Orphanin FQ/Nociceptin in the ventromedial nucleus facilitates lordosis.. NeuroReport 1997; 8: 3857 - 3860.
Blanco, C., Popper, P. and Micevych, P. E Pharmacological doses of testosterone and up-regulate choline-acetyltransferase mRNA.. Neuroscience 1997; 78(3): 873 - 882.
Saldanha, CJ Schlinger, BA Micevych, PE Horvath, TL Presynaptic N-methyl-D-aspartate receptor expression is increased by estrogen in an aromatase-rich area of the songbird hippocampus.. The Journal of comparative neurology. . 2004; 469(4): 522-34.
Mills, RH Sohn, RK Micevych, PE Estrogen-induced mu-opioid receptor internalization in the medial preoptic nucleus is mediated via neuropeptide Y-Y1 receptor activation in the arcuate nucleus of female rats.. The Journal of neuroscience : the official journal of the Society for Neuroscience. . 2004; 24(4): 947-55.
Quesada, A Micevych, PE Estrogen interacts with the IGF-1 system to protect nigrostriatal dopamine and maintain motoric behavior after 6-hydroxdopamine lesions.. Journal of neuroscience research. . 2004; 75(1): 107-16.
Micevych, P Sinchak, K Mills, RH Tao, L LaPolt, P Lu, JK The luteinizing hormone surge is preceded by an estrogen-induced increase of hypothalamic progesterone in ovariectomized and adrenalectomized rats.. Neuroendocrinology. . 2003; 78(1): 29-35.
Sinchak, K Micevych, P Visualizing activation of opioid circuits by internalization of G protein-coupled receptors.. Molecular neurobiology.. 2003; 27(2): 197-222.
Micevych, PE Rissman, EF Gustafsson, JA Sinchak, K Estrogen receptor-alpha is required for estrogen-induced mu-opioid receptor internalization.. Journal of neuroscience research. . 2003; 71(6): 802-10.
Micevych, P Chaban, V Quesada, A Sinchak, K Oestrogen modulates cholecystokinin: opioid interactions in the nervous system.. Pharmacology & toxicology. . 2002; 91(6): 387-97.
Mills, RH Romeo, HE Lu, JK Micevych, PE Site-specific decrease of progesterone receptor mRNA expression in the hypothalamus of middle-aged persistently estrus rats.. Brain research. . 2002; 955(1-2): 200-6.
Raji-Kubba, J Micevych, PE Simmons, DD The superior olivary complex of the hamster has multiple periods of cholinergic neuron development.. Journal of chemical neuroanatomy. . 2002; 24(2): 75-93.
Cristobal, R Popper, P Lopez, I Micevych, P De Vellis, J Honrubia, V In vivo and in vitro localization of brain-derived neurotrophic factor, fibroblast growth factor-2 and their receptors in the bullfrog vestibular end organs.. Brain research. Molecular brain research. . 2002; 102(1-2): 83-99.
Micevych, P Sinchak, K Estrogen and endogenous opioids regulate CCK in reproductive circuits.. Peptides. . 2001; 22(8): 1235-44.
Sinchak, K Micevych, PE Progesterone blockade of estrogen activation of mu-opioid receptors regulates reproductive behavior.. The Journal of neuroscience : the official journal of the Society for Neuroscience. . 2001; 21(15): 5723-9.
Popper, P Lopez, I Beizai, P Li, G Kim, J Micevych, PE Honrubia, V Expression of BDNF and TrkB mRNAs in the crista neurosensory epithelium and vestibular ganglia following ototoxic damage.. Brain research. . 1999; 846(1): 40-51.
Lewis, MI Fournier, M Yeh, AY Micevych, PE Sieck, GC Alterations in diaphragm contractility after nandrolone administration: an analysis of potential mechanisms.. Journal of applied physiology (Bethesda, Md. : 1985) . 1999; 86(3): 985-92.
Eckersell, CB Popper, P Micevych, PE Estrogen-induced alteration of mu-opioid receptor immunoreactivity in the medial preoptic nucleus and medial amygdala.. The Journal of neuroscience : the official journal of the Society for Neuroscience. . 1998; 18(10): 3967-76.
Don, DM Newman, AN Micevych, PE Popper, P Expression of brain-derived neurotrophic factor and its receptor mRNA in the vestibuloauditory system of the bullfrog.. Hearing research. . 1997; 114(1-2): 10-20.
Olive, MF Anton, B Micevych, P Evans, CJ Maidment, NT Presynaptic versus postsynaptic localization of mu and delta opioid receptors in dorsal and ventral striatopallidal pathways.. The Journal of neuroscience : the official journal of the Society for Neuroscience. . 1997; 17(19): 7471-9.
Research Interest:

The research of the laboratory is focused on steroid hormone interactions with the central nervous system. Throughout life, sex steroid hormones profoundly influence the structure and function of specific circuits that regulate reproduction and reproductive behaviors. Previous work had focused on the regulation of neuropeptide and transmitter expression. However, relatively little is known about the mechanisms by which steroids affect postsynaptic activation and signal transduction. The laboratory has three major interests: STEROID MODULATION OF mu-OPIOID RECEPTOR (MOR) ACTIVATION Estrogen treatment of ovariectomized rats initially has an inhibitory action on circuits mediating sexual receptivity (lordosis), but eventually induces sexual receptivity. We have determined that an important component of this inhibition is due to the activation of MOR circuits in the medial preoptic area. Taking advantage of G protein-coupled receptor (GPCR) internalization following activation of the receptor by an endogenous ligand, we determined that activation of MOR is correlated with an inhibition of lordosis. Behaviorally, progesterone augments estrogen action. We have determined that progesterone relieves MOR-mediated inhibition, through the termination of opioid release in the medial preoptic area. Is the MOR-inhibition dependent on estrogen receptors? Working with Dr. Emilie Rissman, (University of Virginia), we have determined that estrogen activation of MOR circuits is dependent on the expression of the estrogen receptor-a (ERa). Although MOR and opioid expression appears nominal in ERa knockout (ERaKO) mice, and MOR-selective opioids internalize MOR, estrogen does not induce internalization. These results and the rapid time course of internalization suggest that the ERa is acting through a nongenomic mechanism. REGULATION OF NEUROSTEROID BIOSYNTHESIS Although it is well known that the brain can synthesize neurosteroids, it has been difficult to determine the function of these steroids in the regulation of reproduction. We have recently determined that peripheral estrogen stimulates the synthesis of progesterone in the hypothalamus. This increased in progesterone is restricted to the hypothalamus and is necessary for the initiation of the LH surge. Examination of cells in vitro suggest that astrocytes are responsible for the estrogen-induced progesterone synthesis. This response to estrogen may be an important component of estrogen positive feedback regulates the LH surge. Males and aging females that do not exhibit positive feedback, that are lacking the ability to increase progesterone synthesis in the hypothalamus. NONGENOMIC ACTIONS OF ESTROGEN MODULATION To begin examining the nongenomic actions of estrogen on regulation of postsynaptic mechanisms, we have studied the response of Ca2+ in dorsal root ganglion (DRG) cells. DRG cells provide an accessible and practical solution to quantitatively study the chemosensitive properties of estrogen-sensitive neurons. These cells express ERa and a number of other well characterized Ca2+ channels. We have been studying the effects of estrogen on modulation of P2X receptors (ATP receptors) and activity of voltage dependent Ca2+ channels (VdCC) using digital videomicroscopy for [Ca2+]i changes. Recent results indicate that 17-beta estradiol inhibited ATP-mediated [Ca2+]i responses and attenuated Ca2+ rise by acting on L-type VDCC in both male and female DRG neurons