Vassiliki Aroniadou-Anderjaska, MS, PhD

Vassiliki Aroniadou-Anderjaska, MS, PhD

Name: Vassiliki Aroniadou-Anderjaska, MS, PhD

USU Department of Primary Appointment: 
Anatomy, Physiology and Genetics
Title: 
Research Professor
Faculty Rank: 
Research Full Professor
Location: 
Uniformed Services University of the Health Sciences, Bethesda, MD

Research Interests:
Development of safe and effective medical countermeasures that can protect military personnel and civilians against nerve agent toxicity and lethality, including nerve agent-induced seizures, brain damage, and associated long-term morbidity.
Physiology and pathophysiology of the amygdala; implications for epilepsy and neuropsychiatric diseases, with emphasis on anxiety disorders, schizophrenia, and autism. Mechanisms of learning and memory at the systems- and cellular/molecular level.

Office Phone: 
(301) 319-4025

Education

1991: Ph.D., Kent State University, Kent, Ohio, and Northeastern Ohio Universities College of Medicine, Rootstown, Ohio
Major: Neuroscience; Minors: Neurophysiology, Reproductive Endocrinology

Thesis Title: Long-term potentiation (LTP) and depression (LTD) in primary visual cortex of juvenile and adult rats: the role of NMDA receptors.


1987: Master’s degree, Kent State University, Kent, Ohio
Major: Exercise Physiology

Thesis Title: Effects of exogenous growth hormone and heavy-resistance exercise on rat skeletal muscle during developmental growth.

1982: B.A., University of Athens, Athens, Greece

Biography

Dr. Vassiliki Aroniadou-Anderjaska has been working for 40 years in Neuroscience research making great contributions to the fields of a) mechanisms of synaptic plasticity underlying learning and memory, and their age-dependency, b) the nature of intra-columnar and inter-columnar synaptic interactions in the cerebral cortex, c) physiology of the olfactory bulb, with high-impact discoveries such as the dendro-dendritic self-excitation of mitral cells and the presence of GABA-B heteroreceptors in the olfactory nerve terminals, and d) physiology of- and synaptic plasticity in the amygdala, with discoveries that have major implications in understanding the molecular/cellular mechanisms underlying stress and anxiety, as well as seizure generation. Since 2006, the primary aim of Dr. Aroniadou-Anderjaska’s work has been to discover novel compounds that can effectively terminate status epilepticus induced by acute nerve agent exposure, and protect against brain damage and the accompanying long-term neurological, cognitive, and emotional deficits. These research efforts have resulted in the discovery of LY293558 (Tezampanel), as a highly efficacious and safe anticonvulsant and neuroprotectant, and have led to the creation of a new company (Proniras), funded by the Biomedical Advanced Research and Development Authority (BARDA), to perform both basic and clinical studies that will advance the development of LY293558 as a new countermeasure against nerve agents.

Detailed Biography:
As a PhD student (Department of Neurobiology, NEOUCOM; mentor: Dr. Timothy J. Teyler), I worked on Long-Term Potentiation (LTP) of synaptic transmission (the cellular mechanism believed to underlie learning and memory functions) in neocortical areas. I was the first to report that LTP can be induced in the visual cortex of both young and adult rats, without manipulating the neuronal circuitry by pharmacologically reducing synaptic inhibition. I found that induction of LTP in the adult neocortex was NMDA receptor-independent, and involved L-type, voltage-gated calcium channels. The importance of voltage-gated calcium channels in synaptic plasticity, in neocortical and other brain regions, was later confirmed by other investigators.

As a post-doctoral fellow (1993, Department of Anatomy, USUHS) in the laboratory of Dr. Asaf Keller, I used electrophysiological and anatomical techniques to study intra- and inter-columnar synaptic interactions and synaptic plasticity, as well as inhibitory pathways in motor and somatosensory/barrel cortex of rats and mice. I demonstrated the capacity of intrinsic synapses in motor and somatosensory cortex to undergo LTP, in both young and adult animals. My studies supported the view that more than one mechanism may participate in the induction of LTP.

As a Research Assistant Professor at the University of Maryland, School of Medicine /Department of Anatomy and Neurobiology, I studied synaptic physiology and plasticity in the rat olfactory bulb. I discovered, for the first time, the presence of GABA(B) heteroreceptors on olfactory nerve terminals. I showed that despite the absence of conventional synapses between GABAergic neurons and glutamatergic olfactory nerve terminals, the presynaptic GABA(B) heteroreceptors are activated –via a paracrine mechanism– by GABA released from juxtaglomerular cells, and mediate both tonic and phasic inhibition of sensory input to the olfactory bulb. In addition, I was the first to present evidence of dendrodendritic self-excitation of mitral cells in the olfactory bulb; this finding provided strong support to the emerging realization that neuronal communication is effected not only via conventional synapses, but also via autocrine and paracrine actions of neurotransmitters (including “fast neurotransmitters” like glutamate).

In 2000, I joined the Department of Psychiatry at USUHS, where my research focus has been in the amygdala, the brain structure that plays a most central role in epilepsy, as well as in emotional behavior and neuropsychiatric diseases. I was the first to demonstrate that field potentials can be recorded from the amygdala, in in vitro brain slices, despite that this structure does not have a laminar organization, and, therefore, it does not generate strong extracellular current dipoles during population activity. Using this preparation, I demonstrated the capacity of the external capsule to basolateral amygdala (BLA) synapses to undergo input-specific LTP and depotentiation. In 2001, in collaboration with Dr. Maria Braga and Dr. He Li, we discovered a novel effect of the anticonvulsant lamotrigine in the amygdala, which could explain the effectiveness of this drug in certain psychiatric illnesses. Our studies on the modulation of GABA release by presynaptic GluK1 (GluR5) kainate receptors in the BLA were part of our efforts to understand the mechanisms regulating neuronal excitability in this brain region, which is central to seizure generation/epilepsy, as well as emotional disorders such as PTSD. Our finding of the reduction of the α1A adrenoceptor-mediated facilitation of GABAergic transmission in the BLA following exposure to stress, provided important insights into the mechanisms that may underlie the hyperexcitability of the amygdala in certain stress-related disorders such as PTSD, the antiepileptogenic effects of norepinephrine in temporal lobe epilepsy, and the stress-induced exacerbation of seizure activity in epileptic patients.

My most recent research efforts, in collaboration with Dr. Braga, have been focused on finding effective antidotes against nerve agent-induced seizures and brain damage. The discoveries from this research have been exceptionally promising and may soon lead to FDA approval of a new anticonvulsant and neuroprotectant against nerve agents, that is effective even if administered with a delay after the exposure; anticonvulsant efficacy at delayed post-exposure time points is particularly important considering that control and monitoring of status epilepticus by medical personnel may not be immediately available in an emergency situation with mass casualties. At the same time, we continue research on the physiology and pathophysiology of the amygdala, with an emphasis on the mechanisms regulating neuronal excitability in the BLA (abnormal excitability of the BLA network is a characteristic feature in anxiety disorders). We have found that activation of GluK1 kainate receptors in the rat BLA facilitates both GABA and glutamate release, but the facilitation of glutamate release prevails, and, therefore, activation of these receptors can have an anxiogenic and seizurogenic net function. In contrast, we found that α(7)-containing nicotinic acetylcholine receptors are active in the basal state enhancing GABAergic inhibition, and their further exogenous activation produces a transient but dramatic increase of spontaneous inhibitory postsynaptic currents in principal BLA neurons, which may underlie the anxiolytic effects of nicotine. We further demonstrated that acid-sensing ion channels (ASICs) also contribute significantly to inhibition of the BLA in the basal state, and activation of these channels produces anxiolytic effects. Most recently, we discovered that the NMDA receptor subtype that contains the GluN2A subunit plays a central role in the regulation of rhythmic inhibition in the BLA, a finding with potentially significant implications for the treatment of schizophrenia, autism, and depressive disorders.

Representative publications, projects, and/or deployments

  • Aroniadou-Anderjaska V, Figueiredo TH, Apland JP, Prager EM, Pidoplichko VI, Miller SL, Braga MF. (2016) Long-term neuropathological and behavioral impairments after exposure to nerve agents. Ann N Y Acad Sci. 1374(1):17-28.
  • Miller SL, Aroniadou-Anderjaska V, Figueiredo TH, Prager EM, Almeida-Suhett CP, Apland JP, Braga MF. (2015) A rat model of nerve agent exposure applicable to the pediatric population: The anticonvulsant efficacies of atropine and GluK1 antagonists. Toxicol Appl Pharmacol. 284:204-216
  • Apland JP, Aroniadou-Anderjaska V, Figueiredo TH, Rossetti F, Miller SL, Braga MF. (2014) The Limitations of Diazepam as a Treatment for Nerve Agent-Induced Seizures and Neuropathology in Rats: Comparison with UBP302. J Pharmacol Exp Ther. 351:359-72.
  • Apland JP, Aroniadou-Anderjaska V, Figueiredo TH, Green CE, Swezey RR, Yang C, Qashu F, Braga MF (2013) Efficacy of the GluK1/AMPA Receptor Antagonist LY293558 Against Seizures and Neuropathology in a Soman-Exposure Model without Pretreatment and its Pharmacokinetics after Intramuscular Administration. J Pharmacol Exp Ther. 344:133-40
  • Figueiredo TH, Aroniadou-Anderjaska V, Qashu F, Apland JP, Pidoplichko V, Stevens D, Ferrara TM, Braga MFM (2011) Neuroprotective efficacy of caramiphen against soman and mechanisms of action. British J. Pharmacol., 164:1495-505.
  • Williams LR, Aroniadou-Anderjaska V, Qashu F, Finne H, Pidoplichko V, Bannon DI, and Braga MFM. (2011) RDX Binds to the GABAA Receptor-Convulsant Site and Blocks GABAA Receptor-Mediated Currents in the Amygdala: a Mechanism for RDX-Induced Seizures. Environmental Health Perspectives. 119:357-363.
  • Aroniadou-Anderjaska V, Figueiredo TH, Apland JP, Qashu F, Braga MF. (2009) Primary brain targets of nerve agents: the role of the amygdala in comparison to the hippocampus. Neurotoxicology 30:772-6.
  • Braga, M.F.M., Aroniadou-Anderjaska, V., Manion, S.T., Hough, CJ and Li, H. (2004) Stress impairs alpha1A adrenoceptor-mediated noradrenergic facilitation of GABAergic transmission in the basolateral amygdala. Neuropsychopharmacology. Vol. 29, 45-58.
  • Braga, M.F.M., Aroniadou-Anderjaska, V., Xie, J. and Li, H. (2003) Bidirectional modulation of GABA release by presynaptic GluR5 kainate receptors in the basolateral amygdala. Journal of Neuroscience. Vol 23, 442-452.
  • Braga, M.F.M., Aroniadou-Anderjaska, V., Post, R.M. and Li H. (2002) Lamotrigine reduces spontaneous and evoked GABAA receptor-mediated synaptic transmission in the basolateral amygdala: Implications for its effects in seizure- and affective disorders. Neuropharmacology, 42, 522-529.

Bibliography

  • Aroniadou-Anderjaska V, Pidoplichko VI, Figueiredo TH, Braga MFM. (2018) Oscillatory Synchronous Inhibition in the Basolateral Amygdala and its Primary Dependence on NR2A-containing NMDA Receptors. Neuroscience, 373:145-158.
  • Pidoplichko V†, Aroniadou-Anderjaska V†, Prager EM, Figueiredo TH, Almeida-Suhett CP, Miller S, and Braga MFM. (2014). ASIC1a activation enhances inhibition in the basolateral amygdala and reduces anxiety. J Neurosci. 34(9):3130-41. (The Journal of Neuroscience had a Press Release based on the findings of our paper) †shared first authorship
  • Aroniadou-Anderjaska V, Brita Fritsch, Felicia Qashu and Maria F.M. Braga (2008) Pathology and Pathophysiology of the Amygdala in Epileptogenesis and Epilepsy. Epilepsy Research, 78(2-3):102-16.
  • Aroniadou-Anderjaska V, Pidoplichko V, Figueiredo TH, Almeida-Suhett CP, Prager EM, and Braga MFM. (2012) Presynaptic Facilitation of Glutamate Release in the Basolateral Amygdala: a Mechanism for the Anxiogenic and Seizurogenic Function of GluK1 receptors. Neuroscience. 221:157-169
  • Aroniadou-Anderjaska V, Felicia Qashu and Maria F.M. Braga (2007) Mechanisms Regulating GABAergic Inhibitory Transmission in the Basolateral Amygdala: Implications for Epilepsy and Anxiety Disorders. Amino Acids, 32:305-15
  • Aroniadou-Anderjaska, V., Zhou FM, Priest CA, Ennis , M. and Shipley M.T. (2000) Tonic and synaptically evoked presynaptic inhibition of sensory input to the rat olfactory bulb via GABA-B heteroreceptors. J. Neurophysiol., 84, 1194-1203.
  • Aroniadou-Anderjaska, V., Ennis , M. and Shipley M.T. (1999) Dendrodendritic recurrent excitation in mitral cells of the rat olfactory bulb. J. Neurophysiol. , 82, 489-494.
  • Aroniadou-Anderjaska, V., Ennis , M. and Shipley M.T. (1999) Current Source Density analysis in the rat olfactory bulb: Laminar distribution of kainate/AMPA and NMDA receptor-mediated currents. J. Neurophysiol., 81, 15-29.
  • Aroniadou, V.A. and Keller, A. (1995) Mechanisms of LTP induction in rat motor cortex in vitro. Cerebral Cortex, 5, 353-362.
  • Aroniadou, V.A. and Keller A. (1993) The patterns and synaptic properties of horizontal intracortical connections in the rat motor cortex. J. Neurophysiol., 70, 1553-1569.