Dr. Veronica Campanucci BSc, MSc, PhD
Associate Professor Anatomy, Physiology and Pharmacology

Education

• PhD - McMaster University (Hamilton)
• BSc, MSc equivalent - Universidad de Buenos Aires (Argentina)

Postdoctoral Experience

• Department of Physiology, McGill University (Montréal)
• Neuroscience and mental Health, The Hospital for Sick Children (Toronto)

Why oxidative stress?

Effect of pathological conditions on the nervous system, especially on mechanisms triggered by oxidative stress.

Why oxidative stress? Among the various forms of stress that neurons can face during pathological conditions, oxidative stress is particularly important because it can be responsible for the onset and/or progression of various devastating diseases. We are particularly interested on diabetes as a model disease associated with the generation of oxidative stress. Elevated blood glucose (hyperglycemia) induces the generation of free radicals such as reactive oxygen species (ROS) in the nervous system, contributing to the morbidity of the disease. ROS is involved in the progression of diabetic neuropathy, which is the most common diabetes-related complication affecting almost half of all people living with the disease. The symptoms vary with the type of neuropathy and can significantly lessen the quality of life of diabetic patients. For example, neuropathy affecting autonomic nerves causes cardiac arrhythmias and poor control of blood pressure (autonomic neuropathy), or affecting sensory nerves can cause abnormal touch and pain perception (sensory neuropathy). These symptoms become more severe with the time that the nervous system is exposed to high plasma glucose, and ultimately are associated with damage to peripheral nerves.

We work on the effect of oxidative stress on receptors from the Cys-loop family (ACh, 5-HT3 and GABA-A), ionotropic purinergic receptors (P2X) and glutamatergic receptors (NMDA). Our current interest resides in understanding the role of oxidation-mediated modulation of neurotransmitter receptors in diabetic sensory neuropathy. To address this interest we work with sensory neurons and sensory synapses from mice and perform molecular biology, electrophysiological and imaging based experiments.

Our approach includes three main research areas:

1) Electrophysiology of sensory neurons and sensory synapses: we use cultures of mouse sensory neurons and study 5HT3 receptor function in hyperglycemic conditions. In addition, we also use co-cultures of dorsal root ganglion neurons and dorsal horn neurons from the spinal cord to study their synaptic connection in vitro. These co-cultures provide a simplified version of the sensory synapse that can be easily and reliably study by electrophysiological experiments. We rely on multiple electrophysiological techniques, such as whole cell, perforated patch and single channel recording.

2) Imaging studies: We use immunofluorescence, ROS imaging and calcium imaging techniques to study the role of 5HT3 receptors in sensory function. We analyze imaging data with the help of an epifluorescence imaging system or confocal microscopy.

We have recently expanded this interest to other proteins that may play an important role in diabetic neuropathy, such as the receptor for advanced glycation end products (RAGE), which is upregulated and contributes to the generation of oxidative stress in sensor neurons during diabetes.

3) Structure function relationship of the reactive oxygen species (ROS)-mediated inactivation of 5HT3 receptors: We use site directed mutagenesis and heterologous expression systems (mammalian cell lines and Xenopus oocytes) to study the involvement of specific amino acids in the inactivation of 5HT3 receptors. We mainly concentrate on intracellular cysteine residues that could be targeted and oxidized by ROS affecting the function of the ion channel.

Once these mutated versions of 5HT3 receptors are functionally expressed in cell lines or Xenopus oocytes we use whole-cell, single channel and two-electrode voltage clamp electrophysiology to characterize their function.

Collaborations

• Dr. Ellis Cooper at McGill University (Montreal, Canada)
• Dr. Tomas Falzone at the University of Buenos Aires (Buenos Aires, Argentina)
• Dr. Matilde Cordero-Erausquin at the Université Louis Pasteur (Strasbourg, France)

Lam D, Momeni Z, Theaker M, Jagadeeshan S, Yamamoto Y, Ianowski JP, Campanucci VA. RAGE-dependent potentiation of TRPV1 currents in sensory neurons exposed to high glucose. PLoS One. 2018 Feb 23;13(2):e0193312.

Luan X, Belev G, Tam JS, Jagadeeshan S, Hassan N, Gioino P, Grishchenko N, Huang Y, Carmalt JL, Duke T, Jones T, Monson B, Burmester M, Simovich T, Yilmaz O, Campanucci VA, Machen TE, Chapman LD, Ianowski JP. Cystic fibrosis swine fail to secrete airway surface liquid in response to inhalation of pathogens. Nat Commun. 2017 Oct 5;8(1):786.

Chandna AR, Kuhlmann N, Bryce CA, Greba Q, Campanucci VA, Howland JG. Chronic maternal hyperglycemia induced during mid-pregnancy in rats increases RAGE expression, augments hippocampal excitability, and alters behavior of the offspring. Neuroscience. 2015 Sep 10;303:241-60.

Chandna AR, Nair M, Chang C, Pennington PR, Yamamoto Y, Mousseau DD, Campanucci VA.  RAGE mediates the inactivation of nAChRs in sympathetic neurons under high glucose conditions.  Eur J Neurosci. 2014 Nov 28.

Luan X, Campanucci VA, Nair M, Yilmaz O, Belev G, Machen TE, Chapman D, Ianowski JP.  Pseudomonas aeruginosa triggers CFTR-mediated airway surface liquid secretion in swine trachea.  Proc Natl Acad Sci U S A. 2014 Sep 2;111(35):12930-5.

Campanucci VA, Dookhoo L, Vollmer C, Nurse CA.  Modulation of the carotid body sensory discharge by NO: an up-dated hypothesis.  Respir Physiol Neurobiol. 2012 Nov 15;184(2):149-57.

Campanucci VA, Krishnaswamy A and Cooper E. Diabetes depress synaptic transmission in autonomic ganglia.Neuron. 2010 Jun 24;66(6):827-34.

Nurse CA and Campanucci VA (2009) Autonomic Nervous System: Carotid Body and Chemoception. In: Larry R. Squire, Editor(s)-in-Chief, Encyclopedia of Neuroscience, Academic Press, Oxford, pp. 855-62.

Campanucci VA, Krishnaswamy A and Cooper E (2008) Mitochondrial reactive oxygen species inactivate neuronal nicotinic acetylcholine receptors and induce long-term depression of fast nicotinic synaptic transmission. J Neurosci,28:1733-44.

Campanucci VA and Nurse CA (2007) Autonomic innervation of the carotid body: Role in efferent inhibition. Special Issue: “Physiology and Pathophysiology of Carotid Body”, Respiratory Physiology & Neurobiology. Resp Physiol & Neurobiol 157: 83-92.

Campanucci VA, Zhang M, Vollmer C and Nurse CA (2006) Expression of multiple P2X receptors by glossopharyngeal neurons projecting to rat carotid body O₂-chemoreceptors: Role in NO-mediated efferent inhibition. J Neurosci, 26:9482-93.

Campanucci VA, Brown ST, Hudasek K, O’Kelly IM, Nurse CA and Fearon IM (2005) O₂-sensing by recombinant TWIK-related halothane-inhibitable K⁺ channel-1 background K⁺ channels heterologously expressed in human embryonic kidney cells. Neuroscience, 135:1087-94.

Campanucci VA and Nurse CA (2005) Biophysical characterization of whole-cell currents in O₂-sensitive neurons from the rat glossopharyngeal nerve. Neuroscience, 132:437-51.

Campanucci VA, Fearon IM and Nurse CA (2003) A novel O₂-sensing mechanism in rat glossopharyngeal neurones mediated by a halothane-inhibitable background K⁺ conductance. J Physiol, 548: 731-743.