Daniel M Johnstone

The University of Sydney · Discipline of Physiology

Of all our organs, the brain is perhaps the best protected from trauma. The skull has evolved to enclose it and, within the skull, the brain floats in a protective bath of cerebrospinal fluid. It is becoming evident, however, that head trauma experienced in young adult life can cause a dementia that appears decades later. The level of trauma that i...

Maternal iron deficiency occurs in 40–50% of all pregnancies and is associated with an increased risk of respiratory disease and asthma in children. We used murine models to examine the effects of lower iron status during pregnancy on lung function, inflammation and structure, as well as its contribution to increased severity of asthma in the offsp...

In recent times, photobiomodulation has been shown to be beneficial in animal models of Parkinson’s disease, improving locomotive behavior and being neuroprotective. Early observations in people with Parkinson’s disease have been positive also, with improvements in the non-motor symptoms of the disease being evident most consistently. Although the...

Pathological forms of the microtubule-associated protein tau are involved in a large group of neurodegenerative diseases named tauopathies, including frontotemporal lobar degeneration (FTLD-tau). K369I mutant tau transgenic mice (K3 mice) recapitulate neural and behavioural symptoms of FTLD, including tau aggregates in the cortex, alterations to ni...

Photobiomodulation (PBM) with low-intensity red to near infrared light elicits neuroprotection in various pre-clinical models and in some clinical contexts, yet the intracellular mechanisms triggered by PBM, and their temporal sequence of modulation, remain unclear. We aimed to address this uncertainty by mapping the temporal transcriptomic respons...

Accumulating evidence highlights links between iron regulation and respiratory disease. Here, we assessed the relationship between iron levels and regulatory responses in clinical and experimental asthma. We show that cell-free iron levels are reduced in the bronchoalveolar lavage (BAL) supernatant of severe or mild-moderate asthma patients and cor...

Increased iron levels and/or dysregulated iron homeostasis occurs in several lung diseases. Here, the effects of iron accumulation on the pathogenesis of pulmonary fibrosis and associated lung function decline was investigated using a combination of murine models of iron overload and bleomycin-induced pulmonary fibrosis, primary human lung fibrobla...

The tissue-protective properties of photobiomodulation (PBM) (low-intensity red to near-infrared light therapy) have been demonstrated for a number of diseases and injuries, including those of the central nervous system. By modifying mitochondrial function and stimulating a mild adaptive stress response, PBM appears to enhance cellular and tissue r...

Objective: The objective of this review is to consider the dual effects of microbiome and photobiomodulation (PBM) on human health and to suggest a relationship between these two as a novel mechanism. Background: PBM describes the use of low levels of visible or near-infrared (NIR) light to heal and stimulate tissue, and to relieve pain and inflamm...

The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is commonly used to model Parkinson’s disease (PD) as it specifically damages the nigrostriatal dopaminergic pathway. Recent studies in mice have, however, provided evidence that MPTP also compromises the integrity of the brain’s vasculature. Photobiomodulation (PBM), the irradiatio...

Alzheimer's disease, the most common form of dementia, was first formally described in 1907 yet its etiology has remained elusive. Recent proposals that Aβ peptide may be part of the brain immune response have revived longstanding contention about the possibility of causal relationships between brain pathogens and Alzheimer's disease. Research has...

The human microbiome is intimately associated with human health, with a role in obesity, metabolic diseases such as type 2 diabetes, and divergent diseases such as cardiovascular and neurodegenerative diseases. The microbiome can be changed by diet, probiotics, and faecal transplants, which has flow-on effects to health outcomes. Photobiomodulation...

Transcranial photobiomodulation (PBM), which involves the application of low-intensity red to near-infrared light (600-1100nm) to the head, provides neuroprotection in animal models of various neurodegenerative diseases. However, the absorption of light energy by the human scalp and skull may limit the utility of transcranial PBM in clinical contex...

Over the past few decades there has been a dramatic increase in scientific research into photobiomodulation (PBM) therapy, both to treat injury or illness and to enhance normal function or performance. More recently, substantial focus has been placed on PBM of the brain and nervous system, with a range of preclinical studies and some clinical trial...

This review brings together observations on the stress-induced regulation of resilience mechanisms in body tissues. It is argued that the stresses that induce tissue resilience in mammals arise from everyday sources: sunlight, food, lack of food, hypoxia and physical stresses. At low levels, these stresses induce an organised protective response in...

Current treatments for Parkinson’s disease (PD) are primarily symptomatic, leaving a need for treatments that mitigate disease progression. One emerging neuroprotective strategy is remote tissue conditioning, in which mild stress in a peripheral tissue (e.g. a limb) induces protection of life-critical organs such as the brain. We evaluated the pote...

We have long accepted that exercise is ‘good for us’; that − put more rigorously − moderate exercise is associated with not just aerobic fitness but also reduced morbidity and reduced mortality from cardiovascular disease and even malignancies. Caloric restriction (moderate hunger) and our exposure to dietary phytochemicals are also emerging as str...

Iron is essential for many biological processes, however, too much or too little iron can result in a wide variety of pathological consequences, depending on the organ system, tissue or cell type affected. In order to reduce pathogenesis, iron levels are tightly controlled in throughout the body by regulatory systems that control iron absorption, s...

Altered iron levels and/or dysregulated iron homeostasis have been associated with a number of lung diseases, however, the mechanisms that underpin these associations, and whether iron plays a role in the pathogenesis of disease, are yet to be fully elucidated. In this study, systemic and pulmonary iron and lung structure and function were assessed...

The low-density lipoprotein receptor-related protein (LRP) is a large multifunctional cell surface membrane receptor capable of binding over 50 ligands. These include molecules important in Alzheimer's disease such as the amyloid β-protein precursor (AβPP), the β-amyloid (Aβ) peptide and apolipoprotein E (ApoE). Full length LRP consists of a 515 kD...

We have reported previously that intracranial application of near-infrared light (NIr) reduces clinical signs and offers neuroprotection in a subacute MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) monkey model of Parkinson’s disease. In this study, we explored whether NIr reduces the gliosis in this animal model. Sections of midbrain (contain...

We have shown previously that when applied separately, 670 nm and 810 nm near infrared light (NIr) reduces behavioural deficits and offers neuroprotection in a MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) mouse model of Parkinson’s disease. Here, we explored the beneficial outcomes when these NIr wavelengths were applied both together, eithe...

Parkinson’s disease (PD) is characterised by progressive loss of motor function and dopaminergic neuron (DN) density. The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is neurotoxic to DN in the mouse substantia nigra yielding PD-like symptoms. Red peppers contain capsaicin that can protect neurons in an in vitro model of acute oxi...

Purpose: To test whether remote ischemic preconditioning (RIP) is protective to photoreceptors, in a light damage model, and to identify mechanisms involved. Methods: A pressure cuff was used to induce ischemia (2 × 5 minutes) in one hind limb of 4- to 6-month-old albino Sprague-Dawley rats raised in dim, cyclic light (12 hours 5 lux, 12 hours d...

Dietary saffron has shown promise as a neuroprotective intervention in clinical trials of retinal degeneration and dementia and in animal models of multiple CNS disorders, including Parkinson's disease. This therapeutic potential makes it important to define the relationship between dose and protection and the mechanisms involved. To explore these...

We have shown previously that near-infrared light (NIr), when applied at the same time as a parkinsonian insult (e.g. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; MPTP), reduces behavioural deficits and offers neuroprotection. Here, we explored whether the timing of NIr intervention-either before, at the same time or after the MPTP insult-was impo...

We have reported previously that intracranial application of near-infrared light (NIr) - when delivered at the lower doses of 25J and 35J - reduces clinical signs and offers neuroprotection in a subacute MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) monkey model of Parkinson's disease. In this study, we explored whether a higher NIr dose (125...

We previously demonstrated elevated brain iron levels in myelinated structures and associated cells in a hemochromatosis Hfe−/−xTfr2mut mouse model. This was accompanied by altered expression of a group of myelin-related genes, including a suite of genes causatively linked to the rare disease family ‘neurodegeneration with brain iron accumulation’...

Presenting results from a mouse model of iron loading.

As recognised by the National Institutes of Health (NIH) Precision Medicine Initiative (PMI), microarray technology currently provides a rapid, inexpensive means of identifying large numbers of known genomic variants or gene transcripts in experimental and clinical settings. However new generation sequencing techniques are now being introduced in m...

Objective: To examine whether near-infrared light (NIr) treatment reduces clinical signs and/or offers neuroprotection in a subacute MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) monkey model of Parkinson's disease. Methods: We implanted an optical fibre device that delivered NIr (670nm) to the midbrain of macaque monkeys, close to the sub...

Alzheimer's and Parkinson's disease are the two most common neurodegenerative disorders. They develop after a progressive death of many neurons in the brain. Although therapies are available to treat the signs and symptoms of both diseases, the progression of neuronal death remains relentless, and it has proved difficult to slow or stop. Hence, the...

The 'neurodegeneration with brain iron accumulation' (NBIA) disease family entails movement or cognitive impairment, often with psychiatric features. To understand how iron loading affects the brain, we studied mice with disruption of two iron regulatory genes, hemochromatosis (Hfe) and transferrin receptor 2 (Tfr2). Inductively coupled plasma atom...

Aberrant brain iron deposition is observed in both common and rare neurodegenerative disorders, including those categorized as Neurodegeneration with Brain Iron Accumulation (NBIA), which are characterized by focal iron accumulation in the basal ganglia. Two NBIA genes are directly involved in iron metabolism, but whether other NBIA-related genes a...

OBJECT The authors of this study used a newly developed intracranial optical fiber device to deliver near-infrared light (NIr) to the midbrain of 6-hydroxydopamine (6-OHDA)-lesioned rats, a model of Parkinson’s disease. The authors explored whether NIr had any impact on apomorphine-induced turning behavior and whether it was neuroprotective. METHO...

Parkinson’s disease (PD) is the second most widespread neurodegenerative disease around the world. It is characterised by the signs of resting tremor, bradykinesia and rigidity. The standard treatments for PD are effective at attenuating the motor signs at least at their onset. However they do not efficiently slow the progression of the PD. In anot...

Iron has been linked to various serious eye diseases including age-related macular degeneration (AMD), however little is known about how iron affects the eye. Recent research in mouse models of hemochromatosis or brain iron loading provides evidence that iron accumulation in the retina can cause tissue pathology and molecular changes however effect...

Glossary Competing endogenous ribonucleic acid (ceRNA) A form of RNAs molecules that regulate other RNA transcripts by competing for shared microRNAs. Complementary deoxyribonucleic acid (cDNA) A form of DNA synthesized from a messenger RNA template in a reaction catalyzed by the enzyme reverse transcriptase. Expressed sequence tags (ESTs) A short...

Age-related macular degeneration (AMD) is responsible for a substantial proportion of severe visual impairment and blindness in people over 50 years of age. Current treatments for AMD are not effective in all patients and a proportion of patients who respond well to the treatment will still eventually develop central visual impairment. Despite all...

Hereditary haemochromatosis is a recessive gene disorder which associated with increased iron absorption and deposition. The implications of iron loading in various organs have been investigated however the direct effects of excessive iron on the retina have been overlooked.

The incidence of intractable age-related neurodegenerative conditions such as Alzheimer's and Parkinson's diseases and age-related macular degeneration is projected to increase substantially over the coming decades with the ageing of the global population. While the burden of disease associated with other chronic conditions has decreased in recent...

ABSTRACT We have used the MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) mouse model to explore whether (i) the neuroprotective effect of near infrared light (NIr) treatment in the SNc is dose-dependent and (ii) the relationship between tyrosine hydroxylase (TH)+ terminal density and glial cells in the caudate-putamen complex (CPu). Mice recei...

Spreading the word about science and inspiring people to connect with the processes and outcomes of science, whether as researchers, educators, students, industry professionals or consumers, is essential in forging stronger links among scientists and with the communities that stand to benefit from their work. How do we nurture inspirational scienti...

We explored whether 810nm near-infrared light (NIr) offered neuroprotection and/or improvement in locomotor activity in an acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mouse model of Parkinson's disease. Mice received MPTP and 810nm NIr treatments, or not, and were tested for locomotive activity in an open-field test. Thereafte...

This review traces evidence that age-related dementia (Alzheimer's disease) results from the destructive impact of the pulse on cerebral vasculature. Evidence is reviewed that the neuropathology of the dementia is caused by the breakdown of small cerebral vessels (silent microbleeds), that the microbleeds result from pulse-induced damage to the cer...

We have previously shown near infrared light (NIr), directed transcranially, mitigates loss of dopaminergic cells in MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-treated mice, a model of parkinsonism. These findings complement others suggesting NIr treatment protects against damage from various insults. However one puzzling feature of NIr tr...

Parkinson’s disease is a movement disorder with cardinal signs of resting tremor, akinesia, and rigidity. These manifest after a progressive death of many dopaminergic neurons of the midbrain. Unfortunately, the progression of this neuronal death has proved difficult to slow and impossible to reverse despite an intense search for the specific cause...

Previous work has demonstrated the efficacy of irradiating tissue with red to infrared light in mitigating cerebral pathology and degeneration in animal models of stroke, traumatic brain injury, parkinsonism and Alzheimer's disease (AD). Using mouse models, we explored the neuroprotective effect of near infrared light (NIr) treatment, delivered at...

Object: Previous experimental studies have documented the neuroprotection of damaged or diseased cells after applying, from outside the brain, near-infrared light (NIr) to the brain by using external light-emitting diodes (LEDs) or laser devices. In the present study, the authors describe an effective and reliable surgical method of applying to th...

Interventions to delay or slow Alzheimer's disease (AD) progression are most effective when implemented at pre-clinical disease stages, making early diagnosis essential. For this reason, there is an increasing focus on discovery of predictive biomarkers for AD. Currently, the most reliable predictive biomarkers require either expensive (brain imagi...

While Illumina microarrays can be used successfully for detecting small gene expression changes due to their high degree of technical replicability, there is little information on how different normalization and differential expression analysis strategies affect outcomes. To evaluate this, we assessed concordance across gene lists generated by appl...

Background We have shown previously that near-infrared light (NIr) treatment or photobiomodulation neuroprotects dopaminergic cells in substantia nigra pars compacta (SNc) from degeneration induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in Balb/c albino mice, a well-known model for Parkinson’s disease. The present study explores whe...

Understanding the response of the brain to haemorrhagic damage is important in haemorrhagic stroke and increasingly in the understanding the cerebral degeneration and dementia that follow head trauma and head-impact sports. In addition, there is growing evidence that haemorrhage from small cerebral vessels is important in the pathogenesis of age-re...

Background: There is growing evidence that the spice saffron, which contains powerful anti-oxidants, offers protection against neurodegenerative disorders, including age-related macular degeneration and Alzheimer's disease. Objective: We examined whether saffron pre-treatment protects dopaminergic cells of the substantia nigra pars compacta (SNc...

Iron abnormalities within the brain are associated with several rare but severe neurodegenerative conditions. There is growing evidence that more common systemic iron loading disorders such as hemochromatosis can also have important effects on the brain. To identify features that are common across different forms of hemochromatosis, we used microar...