Research Interest, Education & Publications

photo of Alvin V. Terry, PhD

Alvin V. Terry, PhD

  • Regent's Professor & Chair
  • Pharmacology & Toxicology

706-721-9462

Research & Education Building, CB 3542

Office phone icon: 706-721-9462
Lab phone icon: 706-721-9514

 

Members of the Lab

Dan Beck, BS

  • Senior Research Associate
  • Small Animal Behavior Core
  • Manager

Yutaka Itokazu, PhD

  • Senior Research Scientist

Marc Plagenhoef

  • Research Assistant
  • Gracewood Facility

Truc Bui

  • Student Assistant
  • Small Animal Behavior Core

RESEARCH INTEREST

My primary research interests focus on the neuronal pathways that are involved in the memory dysfunction associated with neurologic and psychiatric illnesses and exposures to environmental toxins. My laboratories also pursue therapeutic discovery and development strategies for disorders of cognition and we employ a variety of methods ranging from behavioral testing in animal models (rodents to non-human primates) to molecular, cellular and analytical techniques (e.g., immunoblotting, ELISA, immunohistochemistry, receptor autoradiography, mass spectrometry, magnetic resonance imaging, etc.)


EDUCATION & POST-DOCTORAL TRAINING

         1992       Postdoctoral Training             Medical College of Georgia

         1991       PhD in Pharmacology             University of South Carolina College of Pharmacy

         1982       BS in Pharmacy                       Medical University of South Carolina


ACADEMIC APPOINTMENTS

2015 - Present      Associate Vice President for Basic Science Research, Augusta University, Augusta, GA

2014 - Present      Chair, Department of Pharmacology & Toxicology, Augusta University, Augusta, GA

2005 - Present      Professor of Neurology (Joint), Augusta University, Augusta, GA

2005 - Present      Professor of Pharmacology & Toxicology, Augusta University, Augusta, GA

2003 - Present      Director, Small Animal Behavior Core, Augusta University, Augusta, GA


HONORS

         2018      Graduate School Outstanding Faculty Award, Augusta University

         2012      Regents’ Professor

         2012      GHSU School of Graduate Studies Distinguished Research Award


CONTRIBUTIONS TO SCIENCE

One major focus of my laboratory is therapeutic discovery and development, specifically for neurologic and psychiatric disorders (e.g., Alzheimer’s disease, schizophrenia, major depression). Via collaborations with medicinal chemists and other scientists in both academia and industry we have focused on developing compounds that act at multiple drug targets and/or have multifunctional activities (e.g., pro-cognitive and antipsychotic and/or neuroprotective properties) and have also evaluated several adjunctive treatment strategies (i.e., combined currently available treatments with other compounds to improve disease symptoms). These studies utilize a variety of model systems ranging from cell culture to behavioral testing in rodents to non-human primates. We have several series of novel compounds in development including positive allosteric modulators (PAMs) of α7-nAChRs, analogs of the nicotine metabolite, cotinine, and analogs of the acetylcholine precursor, choline. We are also in the process of evaluating deep brain (electrical) stimulation of the nucleus basalis of Meynert as a pro-cognitive strategy in monkeys as well as repurposing and adjunctive treatment strategies.

Representative Publications:
1. Dinkins M, Enasko J, Hernandez C, Wang G, Kong JN, Helwa I, Liu Y, Terry A Jr, Bieberich E. Neutral sphingomyelinase-2 deficiency ameliorates Alzheimer's disease pathology and improves cognition in the 5XFAD mouse. Journal of Neuroscience 36: 8653-8667, 2016. PMCID: PMC4987436
2. Callahan PM, Bertrand D, Bertrand S, Plagenhoef MR, Terry AV Jr. Tropisetron sensitizes α7 containing nicotinic receptors to low levels of acetylcholine in vitro and improves memory-related task performance in young and aged animals. Neuropharmacology 117:422-433, 2017. PMID: 28259598
3. Liu R, Crawford J, Callahan PM, Terry AV Jr, Constantinidis C, Blake DT. Intermittent Stimulation of the Nucleus Basalis of Meynert Improves Working Memory in Adult Monkeys. Current Biology 27:2640-2646, 2017. PMID: 28823679
4. Callahan PM, Plagenhoef MR, Blake DT, and Terry AV Jr. Atomoxetine improves memory and other components of executive function in young-adult rats and aged rhesus monkeys. Neuropharmacology 155: 65-75, 2019. PMID: 31108108

Another scientific area that I am especially interested in is cognition in neuropsychiatric disorders such as schizophrenia, autism, and major depression, and how the symptomatic treatments of these diseases (especially antipsychotic drugs) affect cognition in animal models. Neuropsychiatric disorders such as schizophrenia and major depression are devastating illnesses that are ranked among the top causes of disability worldwide and among their varied symptoms, cognitive dysfunction may be one of the most important factors that affects long-term functional outcome. However, our current understanding of how antipsychotics affect cognition over time remains inadequate. I and my collaborators have published extensively in this area over the last 13-14 years. Our work to date in animal models has established that both first and second generation antipsychotics can negatively affect some domains of cognition (e.g., attention, spatial learning and memory) if administered for sufficiently long periods of time.  Furthermore we have established that the mechanisms for these impairments may involve deleterious effects on cholinergic proteins and growth factors (NGF, BDNF). We have also evaluated several pro-cognitive therapeutic strategies to improve cognition in animals that have been chronically treated with antipsychotics. We have also evaluated both potential environmental and genetic factors (e.g., prenatal stress, Transglutaminase 2 overexpression) that may contribute to abnormal behaviors in adult animals (e.g., impulsivity and depression-like behaviors).

Representative publications:
1. Terry, AV., Jr., Parikh V, Gearhart DA, Pillai, Hohnadel EJ, Warner, S, Nasrallah, HA, and Mahadik SP. Time Dependent Effects of Haloperidol and Ziprasidone on Nerve Growth Factor, Cholinergic Neurons, and Spatial Learning in Rats. Journal of Pharmacology and Experimental Therapeutics 318:709-724, 2006. PMID: 16702442
2. Wilson CA, Schade R, Terry AV Jr. Variable prenatal stress results in impairments of sustained attention and inhibitory response control in a 5-choice serial reaction time task in rats. Neuroscience 218:126-137, 2012. PMID: 22634506
3. Pandya CD, Hoda N, Crider A, Peter D, Kutiyanawalla A, Kumar S, Ahmed AO, Turecki G, Hernandez CM, Terry AV Jr, Pillai A. Transglutaminase 2 overexpression induces depressive-like behavior and impaired TrkB signaling in mice. Molecular Psychiatry 22:745-753, 2017. PMID: 27620841
4. Poddar I, Callahan PM, Hernandez CM, Yang X, Bartlett MG, and Terry AV Jr. Tropisetron enhances recognition memory in rats chronically treated with risperidone or quetiapine. Biochemical Pharmacology 151: 180–187, 2018. PMID: 29175423

An additional interest of my laboratory is how repeated exposures to organophosphates (OPs) affect cognitive function. OPs are highly toxic chemicals that are almost ubiquitous in our environment and, accordingly, they pose a significant health risk to millions of people worldwide. While the acute toxicity of OPs has been studied extensively, the effects of repeated exposures to levels not associated with symptoms of acute toxicity, especially on cognition and the neuronal processes that support cognition, are poorly understood. I and my collaborators have been investigating this issue in model systems for more than 14 years. We have determined that indeed this type of OP exposure can result in persistent impairments in cognition, thus our long-term goal is to determine the mechanism of these adverse effects so that effective therapeutic strategies can be developed. We have determined that deleterious OP-related effects on axonal transport and other targets beyond that normally associated with OP toxicity (acetylcholinesterase) may contribute to the neurobehavioral effects. Over the last 10 years, we have contributed extensively to the literature in this area and have refined our techniques for evaluating OP effects on cognition and for determining OP-related mechanisms that may contribute to the cognitive effects. We progressed from relatively simple learning/memory tasks (e.g., water maze) to more sophisticated operant procedures (e.g., the five choice serial reaction time task) and determined that insecticide OPs and nerve agent OPs have persistent (and in some cases differential) effects on cognition depending on the domain evaluated. Likewise, in the axonal transport studies, we have moved from relatively simple, ex vivo (peripheral) sciatic nerve preparations to ex vivo brain histology to currently employing highly sophisticated live cell imaging methods (in primary CNS neurons) and studying axonal transport in brains of live rats using manganese-enhanced magnetic resonance imaging (MEMRI).

Representative publications:
1. Terry AV Jr., Gearhart DA, Beck WD, Truan JN, Middlemore, ML, Williamson LN, Bartlett MG, Prendergast MA, Sickles DW, and Buccafusco JJ. Chronic, Intermittent Exposure to Chlorpyrifos in Rats: Protracted Effects on Axonal Transport, Neurotrophin Receptors, Cholinergic Markers, and Information Processing. Journal of Pharmacology and Experimental Therapeutics 322: 1117-1128, 2007. PMID: 17548533
2. Terry AV Jr, Callahan PM, Beck WD, Vandenhuerk L, Sinha S, Bouchard K, Schade R, Waller JL. Repeated exposures to diisopropylfluorophosphate result in impairments of sustained attention and persistent alterations of inhibitory response control in rats. Neurotoxicology and Teratology 44:18-29, 2014. PMCID: PMC4099306
3. Naughton SX, Hernandez CM, Beck WD, Poddar I, Yanasak N, Lin PC, Terry AV Jr. Repeated exposures to diisopropylfluorophosphate result in structural disruptions of myelinated axons and
persistent impairments of axonal transport in the brains of rats. Toxicology 406-407:92-103, 2018. PMID: 29894704
4. Naughton SX, Beck WD, Wei Z, Wu G, Terry AV Jr. Multifunctional compounds lithium chloride and methylene Blue attenuate the negative effects of diisopropylfluorophosphate on axonal transport in rat cortical neurons. Toxicology. 2020; 431:152379. doi:10.1016/j.tox.2020.152379. PMID: 31962143

 

Complete List of Published Work in MyBibliography