Melissa M J Farnham

Melissa M J Farnham
Heart Research Institute | HRI

PhD

About

43
Publications
4,358
Reads
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581
Citations
Additional affiliations
January 2019 - present
Heart Research Institute
Position
  • Unit Leader
January 2015 - December 2018
Heart Research Institute
Position
  • Research Officer
February 2012 - April 2012
The University of Calgary
Position
  • University of Calgary
Education
February 2007 - September 2009
Macquarie University
Field of study
  • Neuroscience
February 2002 - November 2006
The University of Sydney
Field of study
  • Physiology and Pharmacology

Publications

Publications (43)
Article
Full-text available
The sympathoadrenal counterregulatory response to hypoglycemia is critical for individuals with type 1 diabetes due to impaired ability to produce glucagon. Ketogenic diets (KD) are an increasingly popular diabetes management tool; however, the effects of KD on the sympathoadrenal response are largely unknown. Here, we determined the effects of KD-...
Article
Full-text available
A key feature of sleep disordered breathing syndromes, such as obstructive sleep apnea is intermittent hypoxia. Intermittent hypoxia is well accepted to drive the sympathoexcitation that is frequently associated with hypertension and diabetes, with measurable effects after just 1 h. The aim of this study was to directly measure the glucose response...
Article
Full-text available
Repetitive hypoxia is a key feature of obstructive sleep apnoea (OSA), a condition characterized by intermittent airways obstruction. Patients with OSA present with persistent increases in sympathetic activity and commonly develop hypertension. The objectives of this study were to determine if the persistent increases in sympathetic nerve activity,...
Article
The RVLM of spontaneously hypertensive rats (SHR) contains over-active C1 neurons, which model the pathology of essential hypertension. Hypertension involves chronic low-grade neuroinflammation. Inflammation in the brain is produced and maintained primarily by microglia. We assessed microglial gene expression (P2Y12R and CX3CR1) and morphology in t...
Article
Full-text available
Activation of neurons in the rostral ventrolateral medulla (RVLM) following glucoprivation initiates sympathoadrenal activation, adrenaline release, and increased glucose production. Here, we aimed to determine the role of RVLM µ-opioid receptors in the counter-regulatory response to systemic glucoprivation. Experiments were performed in sodium pen...
Article
Respiration and blood pressure are primarily controlled by somatic and autonomic motor neurones, respectively. Central cardiorespiratory control is critical in moment-to-moment survival, but it also has a role in the development and maintenance of chronic pathological conditions such as hypertension. The glial cells of the brain are non-neuronal ce...
Article
Autonomic reflex responses are critical in restoring changes to circulatory factors reduced beyond the domain of homeostasis. Intermittent hypoxia triggers repeated activation of chemoreflexes, resulting in baroreflex dysfunction and widespread changes in cellular and neuronal activity regulated by sensory/motor pathways. Hypoglycaemia initiates a...
Article
Full-text available
Background and purpose: Intermittent hypoxia causes a persistent increase in sympathetic activity, which progresses to hypertension in chronic conditions such as obstructive sleep apnea (OSA). Pituitary adenylate cyclase activating polypeptide (PACAP) is an excitatory neurotransmitter that causes long-lasting sympathetic excitation. We aimed to de...
Article
Full-text available
Key points: Activity-dependent plasticity can be induced in carotid body (CB) chemosensory afferents without chronic intermittent hypoxia (CIH) preconditioning by acute intermittent hypoxia coincident with bouts of hypercapnia (AIH-Hc). Several properties of this acute plasticity are shared with CIH-dependent sensory long-term facilitation (LTF) i...
Article
The incidence of sudden unexpected death in epilepsy (SUDEP) is highest in people with chronic and drug resistant epilepsy. Chronic spontaneous recurrent seizures cause cardiorespiratory autonomic dysfunctions. Pituitary adenylate cyclase-activating polypeptide (PACAP) is neuroprotective, whereas microglia produce both pro- and anti- inflammatory e...
Article
Full-text available
Intermittent hypoxia causes a persistent increase in sympathetic nerve activity (SNA), which progresses to hypertension in conditions such as obstructive sleep apnoea. Orexins (A and B) are hypothalamic neurotransmitters with arousal-promoting, and sympathoexcitatory effects. We investigated whether the sustained elevation of SNA, termed sympatheti...
Article
Microglia are present throughout the central nervous system (CNS) and express receptors for every known neurotransmitter. During inflammation, microglia change into a state that either promotes removal of debris (M1), or into a state that promotes soothing (M2). Caudal- and rostral- ventrolateral medullary regions (CVLM and RVLM, respectively) of t...
Article
Microglia are ubiquitously distributed throughout the central nervous system (CNS) and play a critical role in the maintenance of neuronal homeostasis. Recent advances have shown that microglia, never resting cells of the CNS, continuously monitor and influence neuronal/ synaptic activity levels, by communicating with neurons with the aid of their...
Article
Intermittent hypoxia induces plasticity in neural networks controlling breathing and cardiovascular function. Studies demonstrate that mechanisms causing cardiorespiratory plasticity rely on intracellular signalling pathways that are activated by specific neurotransmitters. Peptides such as serotonin, PACAP and orexin are well-known for their physi...
Article
Full-text available
Cardiovascular autonomic dysfunction in seizure is a major cause of sudden unexpected death in epilepsy. The catecholaminergic neurons in the rostral ventrolateral medulla (RVLM) maintain sympathetic vasomotor tone and blood pressure through their direct excitatory projections to the intermediolateral (IML) cell column. Glutamate, the principal exc...
Article
Identification of neurons, and their phenotype, that are activated in response to specific stimuli is a critical step in understanding how neural networks integrate inputs to produce specific outputs. Here, we developed novel mouse monoclonal antibodies of different IgG isotypes that are specific to tyrosine hydroxylase (TH), and to tyrosine hydrox...
Article
For the first time the efficiency of gene knockdown of the pituitary adenylate cyclase-activating polypeptide (PACAP) receptor 1 (PAC1R) is demonstrated by employing gold nanocomplexes. This gene knockdown subsequently affects the action of PACAP on neurite outgrowth in PC12 cells. These nanocomplexes comprise cholera toxin B (CTB)-gold nanoparticl...
Article
The effect of angiotensin II type I receptor (AT1R) inhibition on the pattern of reflex sympathetic nerve activity (SNA) to multiple target organs in the Lewis polycystic kidney (LPK) rat model of chronic kidney disease was determined. Mean arterial pressure (MAP), splanchnic SNA (sSNA), renal SNA (rSNA) and lumbar SNA (lSNA) were recorded in ureth...
Article
Full-text available
Seizures are accompanied by cardiovascular changes that are a major cause of sudden unexpected death in epilepsy (SUDEP). Seizures activate inflammatory responses in the cardiovascular nuclei of the medulla oblongata and increase neuronal excitability. Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide with autocrine and p...
Article
Full-text available
Neuronal stimulation by light is a novel approach in the emerging field of optogenetics, where genetic engineering is used to introduce light activated channels. However light is also capable of stimulating neurons even in the absence of genetic modifications, through a range of physical and biological mechanisms. As a result, rigorous design of op...
Article
The activity of neurons in the rostral ventrolateral medulla (RVLM) is critical for the generation of vasomotor sympathetic tone. Multiple pre-sympathetic pathways converge on spinally projecting RVLM neurons, but the origin and circumstances in which such inputs are active are poorly understood. We have previously shown that input from the contral...
Chapter
Many laboratories around the world use baroreceptor denervation in their investigations of the cardiovascular system. The most common method, performed in the rat, is a permanent denervation where the carotid sinus and aortic depressor nerves are transected. Here, we describe detailed step-by-step methods for acute reversible baroreceptor denervati...
Book
Activation, inhibition, or destruction of the nervous system or its component parts as a vital tool for the investigation of function has undergone remarkable development; indeed, new approaches have been developed that allow for these actions to be used as therapeutic tools. In Stimulation and Inhibition of Neurons, experts in the field provide an...
Article
Full-text available
Pituitary adenylate cyclase-activating polypeptide (PACAP) is an excitatory neuropeptide that plays an important role in hypertension and stress responses. PACAP acts at three G protein-coupled receptors [PACAP type 1 receptor (PAC(1)) and vasoactive intestinal peptide receptor types 1 and 2 (VPAC(1) and VPAC(2))] and is localized to sites involved...
Article
Full-text available
This study focuses on presympathetic neurons of the rostral ventrolateral medulla (RVLM) that regulate sympathetic vasomotor tone. Many neurotransmitters are colocalized in RVLM neurons and are released under specific conditions to modulate efferent homeostatic responses. Of particular interest here are two peptides colocalized in catecholaminergic...
Article
Background and purpose: Pituitary adenylate cyclase-activating polypeptide (PACAP) is an excitatory neuropeptide with central and peripheral cardiovascular actions. Intrathecal PACAP increases splanchnic sympathetic nerve activity and heart rate, but not mean arterial pressure (MAP). We hypothesize that the three PACAP receptors (PAC(1) , VPAC(1)...
Article
Full-text available
A critical function of cells is the maintenance of their genomic integrity. A family of phosphoinositide-3-kinase-related protein kinases, which includes ataxia telangiectasia mutated (ATM) and ataxia telangiectasia and Rad3 related (ATR) kinases, play key roles in sensing DNA damage. ATM and ATR were demonstrated in the cleavage stages of mouse em...
Article
Full-text available
The rostral ventrolateral medulla differentially regulates sympathetic output to different vascular beds, possibly through the release of various neurotransmitters and peptides that may include pituitary adenylate cyclase-activating polypeptide (PACAP). An intrathecal administration of PACAP increases splanchnic sympathetic nerve activity and heart...
Article
Pituitary adenylate cyclase activating polypeptide (PACAP) plays a role in almost every biological process from reproduction to hippocampal function. One area where a role for PACAP is not clearly delineated is central cardiorespiratory regulation. PACAP and its receptors (PAC1, VPAC1 and VPAC2) are present in cardiovascular areas of the ventral me...
Article
Full-text available
The rostral ventrolateral medulla contains presympathetic neurons that project monosynaptically to sympathetic preganglionic neurons (SPN) in the spinal cord and are essential for the tonic and reflex control of the cardiovascular system. SPN directly innervate the adrenal medulla and, via postganglionic axons, affect the heart, kidneys, and blood...
Article
Sinoaortic denervation is a common method used in the investigation of function in the cardiovascular system. In the rat, this is usually accomplished by transection of the carotid sinus and aortic depressor nerves, which is permanent. We propose a novel, and simple method for acute baroreceptor denervation in the rat in which the region around the...
Article
Controversy surrounds the respiratory responses to baroreceptor activation. Although many reflexes that effect respiration (e.g. chemoreflexes and nociceptive reflexes) frequently affect cardiovascular parameters, the effect of baroreflex stimulation within normal physiological limits is generally considered to affect only blood pressure and heart...
Article
1. Cardiovascular sympathetic nerve activity at rest is grouped into waves, or bursts, that are generally, although not exclusively, related to the heart rate and to respiration. In addition, activity is also generated in response to central commands and to environmental stimuli. 2. Responsibility for the integration of all these different elements...
Article
Full-text available
Pituitary adenylate cyclase-activating polypeptide (PACAP) is an excitatory neuropeptide present in the rat brain stem. The extent of its localization within catecholaminergic groups and bulbospinal sympathoexcitatory neurons is not established. Using immunohistochemistry and in situ hybridization, we determined the extent of any colocalization wit...

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Projects

Projects (4)
Archived project
To assess the role of the excitatory neuropeptide, PACAP, in the sympathoexcitatory effects of seizure.