Ursula H. Winzer-Serhan, Ph.D.

Associate Professor
Department of Neuroscience and Experimental Therapeutics
Interdisciplinary Program in Neuroscience (TAMU/TAMHSC)

Phone: 979-845-2860
Fax: 979-845-0699
Email: uwserhan@medicine.tamhsc.edu

Education

Ph.D., Cell Biology, University of Bremen, Germany, 1989

Research Associate, Dept. of Pharmacology, U.C.-Irvine

Research Interests

My lab is investigating the effects of nicotine on brain development. Nicotine passes rapidly through the placenta and into the fetus, where the drug interacts with nicotinic acetylcholine receptors (nAChR), ligand-gated pentameric ion channels, which are normally activated by the endogenous ligand acetylcholine. nAChR subunits can form different nicotinic receptor subtypes depending on their subunit compositions. My recent studies have focused on the developmental expression of nAChR subunits in prenatal and postnatal brain, using in situ hybridization and receptor autoradiography. The results show that nAChRs are widely expressed during embryonic and postnatal development (see Figure) and therefore, untimely activation with nicotine could influence developmental processes such as apoptosis, differentiation or synaptogenesis. Furthermore, stimulation of nAChRs can change the gene expression pattern and induce long-term changes in the developing brain.

On-going projects:

1. Evaluating the effects of chronic nicotine treatment on brain development.
   Nicotine is a recreational drug used by 20 % of pregnant women in the Western world. Nicotine exposure in utero can result in behavioral and cognitive deficits. To investigate nicotine’s effect on brain development, we developed a neonatal rat model of chronic nicotine treatment that corresponds developmentally to the third trimester in humans, a period of active brain growth and synaptogenesis (growth spurt period). In this postnatal model, the pups are intubated two to three times a day to deliver the drug mixed in infant formula. The model allows 1. Exact dosing of nicotine; 2. Use of littermates as controls; 3. Intermittent nicotine release, mimicking a more “natural” situation; 4. No maternal deprivation. The effects of nicotine are being evaluated on a behavioral, structural (using histological staining and immunohistochemistry), and molecular level (using gene array analysis, RT-PCR, in situ hybridization), with emphasis on brain structures involved in cognitive functions, such as hippocampus and cortex.
2. Mapping of the expression of nAChR subunits in the brain using anatomical techniques such as in situ hybridization, receptor autoradiography.
   The focus is on characterizing the expression of nAChR subunits in neuronal sub-populations such as cholinergic and GABAergic neurons, to determine the subtype(s) expressed in these neurotransmitter synthesizing cells. nAChRs are often localized at presynaptic nerve terminals, where they regulate neurotransmitter release. Nicotine stimulates the release of dopamine, serotonin, noradrenalin and acetylcholine, thus, interacting with numerous transmitter systems. Of particular interest for cognitive functions is the basal forebrain cholinergic system, which projects to hippocampus and cortex. Using double in situ hybridization, we found that the expression profile for nAChR subunits in cholinergic neurons is fundamentally different than in dopaminergic neurons, suggesting significant pharmacological and physiological differences in receptor subtypes. We are in the process of further determining the molecular (single cell RT-PCR), pharmacological and physiological characteristics (whole cell recordings) of nAChRs on cholinergic neurons, which is not only important for developmental processes, but also for the mature brain.

Example for the expression of the alpha7 nAChR subunit in the hippocampus of a newborn rat pup. The mRNA coding for alpha7 is detected by in situ hybridization using a subtype specific probe (left side). The receptor protein is detected by receptor autoradiography using 125I alpha-Bungarotoxin, a ligand specific for the alpha7 nAChR (right side).

I participate in graduate training as a member of the faculty in the Interdisciplinary Program in Neuroscience.

Selected Publications

Winzer-Serhan, UH, Leslie, FM. (2004): Developmental expression of ?5 nicotinic acetylcholine receptor subunit mRNA during cortical and hippocampal development in the rat. J. Comp. Neurol. (in press).

Huang, LZ, Hsiao, SH, Armstrong, G, Griffith, WH, Frye, GD, Winzer-Serhan, UH. (2004) Early postnatal chronic nicotinic treatment reduces weight gain in rat pups in a gender specific manner. Soc. Neurosci. Program No. 918.4.

Winzer-Serhan, UH, Chen, Y, and Leslie, FM. Expression of opioid peptides and receptors in striatum and substantia nigra during rat brain development. J. Chem. Neuroanat. Aug; 26(1):17-36, 2003.

Azam L, Winzer-Serhan, UH, Leslie, FM. Co-expression of ?7 and ?2 nicotinic acetylcholine receptor subunit mRNAs within rat brain cholinergic neurons. Neurosci. In press, 2003.

Adams CE, Broide RS, Chen Y, Winzer-Serhan UH, Henderson TA, Leslie FM, Freedman R. Development of ?7 nicotinic cholinergic receptor in rat hippocampal formation. 139(2):175-187, 2002.

Winzer-Serhan, UH. Induction of c-fos mRNA expression after acute nicotine administration in neonates. Soc. Neurosci. Abstract, 2002.Azam, L, Winzer-Serhan, UH, Chen, Y, Leslie, FM. Expression of neuronal nicotinic acetylcholine receptor subunit mRNAs within midbrain dopamine neurons. J Comp Neurol. 444(3):260-74, 2002.

Winzer-Serhan, UH, Leslie, FM. Quantitative light microscopic autoradiography of alpha 2-adrenergic radiogland binding sites. Methods Mol Biol. 126:507-517, 2000. Review.Shi ,TS, Winzer-Serhan, UH, Leslie, F, Hokfelt, T. Distribution and regulation of alpha(2)-adrenoceptors in rat dorsal root ganglia. Pain. 84(2-3):319-330, 2000.

Shi, TS, Winzer-Serhan, UH, Leslie, F, Hokfelt, T. Distribution of alpha2-adrenoceptor mRNAs in the rat lumbar spinal cord in normal and axotomized rats. Neuroreport. 10(13):2835-2839, 1999.

Winzer-Serhan, UH, Leslie, FM. Expression of alpha2A adrenoceptors during rat neocortical development. J Neurobiol. 38(2):259-269, 1999.

Winzer-Serhan, UH, Broide, RS, Chen, Y, Leslie, FM. Highly sensitive radioactive in situ hybridization using full length hydrolyzed riboprobes to detect alpha 2 adrenoceptor subtype mRNAs in adult and developing rat brain. Brain Res Brain Res Protoc. 3(3):229-241, 1999.

Leslie, FM, Chen Y, Winzer-Serhan, UH. Opioid receptor and peptide mRNA expression in proliferative zones of fetal rat central nervous system. Can J Physiol Pharmacol. 76(3):284-293, 1998.

Winzer-Serhan, UH, Leslie, FM., Codistribution of nicotinic acetylcholine receptor subunit alpha3 and beta4 mRNAs during rat brain development. J Comp Neurol. 1997 Oct 6; 386(4):540-554.

Winzer-Serhan, UH, Leslie, FM. Alpha2B adrenoceptor mRNA expression during rat brain development. Brain Res Dev Brain Res. 100(1):90-100, 1997.

Jensen, JJ, Winzer-Serhan, UH, Leslie, FM. Glial regulation of alpha 7-type nicotinic acetylcholine receptor expression in cultured rat cortical neurons. J Neurochem. 68(1):112-120, 1997.

Winzer-Serhan, UH, Raymon, HK, Broide, RS, Chen, Y, Leslie, FM. Expression of alpha 2 adrenoceptors during rat brain development--II. Alpha 2C messenger RNA expression and [3H]rauwolscine binding. Neuroscience. 76(1):261-272, 1997.

Winzer-Serhan, UH, Raymon, HK, Broide, RS, Chen, Y, Leslie, FM. Expression of alpha 2 adrenoceptors during rat brain development--I. Alpha 2A messenger RNA expression. Neuroscience. 76(1):241-260, 1997.