Gene-environmental interactions shape the brain in adults and during development. My lab is particularly interested in exogenous factors that can permanently alter brain function and subsequently behavior. Currently, we study the drug nicotine and how developmental exposure changes brain function, anatomy and behavior. Nicotine interacts with nicotinic acetylcholine receptors (nAChR) which are ligand-gated pentameric cation channels found throughout the central, peripheral and enteric nervous systems. We mapped the expression of nAChRs in prenatal, postnatal and adult brain, using in situ hybridization and receptor autoradiography, and showed early and robust expression of nAChRs throughout development and in adults. We developed a neonatal exposure model in rats which mimics exposure during the third trimester of human brain development, and demonstrated that nicotine treatment during the first postnatal week results in increased anxiety and an altered balance of excitatory / inhibitory synaptic transmission in hippocampal slices. Nicotinic receptors play key roles in neurological diseases such as schizophrenia, autism, ADHD, anxiety, depression, addiction, Alzheimer’s and Parkinson’s disease. To identify the underlying mechanisms through which nicotine and nicotinic receptors alter brain function either during development or in adults, is a fundamental goal of our research and might shed light on developmental and age-related neurological diseases.
I participate in graduate training as a member of the faculty of the Texas A&M Institute for Neuroscience and in the Texas A&M Health Science Center interdisciplinary graduate program in Biomedical Sciences.
Former Graduate Students: Luping Z Huang, Jong-Hyun Son, Pei-San Huang, Joanne C. Damborsky
1. Evaluating the effects of chronic nicotine exposure on brain development.
We study the effects of developmental nicotine exposure using a variety of different approaches which include behavioral, anatomical (receptor autoradiography, immunohistochemistry), molecular (RT-PCR, in situ hybridization), and electrophysiological methods, in brain structures involved in cognitive functions, such as hippocampus and cortex. The main focus is on excitatory glutamatergic and inhibitory GABAergic neurotransmitter systems, where we detect changes on an anatomical and functional level.
Example for the robust expression of alpha7 nAChRs in the hippocampus of a newborn rat. 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).
2. What is the role of nAChRs during aging?
During aging, nACHRs have a very different role. Activation of nAChRs engages anti-apoptotic intracellular signaling pathways resulting in neuroprotection and prevention against neuronal cell death in vitro and in whole animals. In humans, smoking is negatively correlated with the development of Parkinson's and Alzheimer's disease. Accordingly, mice lacking heteromeric nAChRs exhibit accelerated aging in cortical regions, critically involved in cognitive functions. The mechanisms are not well understood but might involve regulation of neurotrophic factors such as NGF, BDNF, IFGI, and FGF2, and activation of survival genes such as SIRT and Nampt, and Ku70, all of which have critical roles in the aging process. We continue to address the question of how nicotinic receptors influence neurodegenerative processes during aging.