Sarah J Spencer

RMIT University | RMIT · School of Health and Biomedical Sciences

Intestinal macrophages are well-studied for their conventional roles in the immune response against pathogens and protecting the gut from chronic inflammation. However, these macrophages may also have additional functional roles in gastrointestinal motility under typical conditions. This is likely to occur via both direct and indirect influences on...

Hyper-activity of the brain’s innate immune cells, microglia, is a hallmark of multiple sclerosis (MS). However, it is not clear whether this involvement of microglia is beneficial or detrimental or whether manipulating microglial activity may be therapeutic. We investigated if inhibiting microglial activity with minocycline prevents the early chan...

One of the chief advantages of using highly standardised biological models including model organisms is that multiple variables can be precisely controlled so that the variable of interest is more easily studied. However, such an approach often obscures effects in sub-populations resulting from natural population heterogeneity. Efforts to expand ou...

The activation of P2X7 is a well-known stimulus for the NLRP3-caspase 1 inflammasome and subsequent rapid IL-1β secretion from monocytes and macrophages. Here we show that positive allosteric modulators of P2X7, ginsenosides, can enhance the release of three important cytokines, IL-1β, IL-6 and TNF-α from LPS-primed rodent macrophages using the J77...

The early-life period represents a time of particular vulnerability to environmental and lifestyle stimuli that can shape our physiology long-term. The neuroimmune system is somewhat immature around the time of birth and a growing body of evidence has illustrated how immune stimuli experienced at this time can have a lasting influence on peripheral...

Rationale: The SARS-CoV2 pandemic led to drastic social restrictions globally. Early data suggest that women in science have been more adversely affected by these lockdowns than men, with relatively fewer scientific articles authored by women. However, these observations test broad populations with many potential causes of disparity. Australia pre...

Microglia have long been thought to be responsible for the initiation of the central nervous system (CNS) immune response to pathogen exposure. However, we recently reported that depleting CNS microglia and circulating monocytes does not abrogate the sickness response in male rats or mice to bacterial endotoxin, lipopolysaccharide (LPS). How the ce...

Gastrointestinal motility is crucial to gut health and has been associated with different disorders such as inflammatory bowel diseases and post-operative ileus. Despite rat and mouse being the two animal models most widely used in gastrointestinal research, minimal studies in rats have investigated gastrointestinal motility. Therefore, our study p...

Ageing causes a gradual deterioration of bodily functions and telomere degradation. Excessive telomere shortening leads to cellular senescence and decreases tissue vitality. Six proteins, called shelterin, protect telomere integrity and control telomere length through telomerase-dependent mechanisms. Exercise training appears to maintain telomeres...

Early life microglia are essential for brain development, and developmental disruption in microglial activity may have long-term implications for the neuroendocrine control of reproduction. We and others have previously shown that early life immune activation compromises the long-term potential for reproductive function in females. However, the sup...

Background and Objective Neurocognitive dysfunction is present in up to ∼61% of people with chronic obstructive pulmonary disease (COPD), with symptoms including learning and memory deficiencies, negatively impacting the quality of life of these individuals. As the mechanisms responsible for neurocognitive deficits in COPD remain unknown, we explor...

Background Due to concerns about risks associated with antidepressants and/or hypnotics, complementary therapies such as acupuncture have been sought by patients with active or previous depression to manage insomnia. This systematic review aimed to clarify if acupuncture is effective and safe enough to be recommended as an alternative or adjuvant t...

Microglia are innate immune cells of the brain. They are acutely activated in response to infection. In our rat Cx3cr1-Dtr knock in model, we have previously found that depletion of microglia and peripheral tissue macrophages upon application of diphtheria toxin (DT) did not abrogate the weight changes, fever generation and increased concentrations...

Chronic obstructive pulmonary disease (COPD) is a major incurable global health burden and currently, the 3rd largest cause of death in the world with approximately 3.23 million deaths per year. Globally, the financial burden of COPD is approximately €82 billion per year and causes substantial morbidity and mortality. Importantly, much of the disea...

Comorbid depression and insomnia are ubiquitous mental complaints among women going through the perimenopausal stage of life and can result in major decline in quality of life. Antidepressive agents combined with/without hypnotics, and/or hormone therapy are currently the most common treatment for perimenopausal depression (PMD) and insomnia (PMI)....

Intestinal macrophages play a key role in the gut immune system and the regulation of gastrointestinal physiology, including gut motility and secretion. Their ability to keep the gut from chronic inflammation despite constantly facing foreign antigens has been an important focus in gastrointestinal research. However, the heterogeneity of intestinal...

The implications of poor maternal diet on offspring metabolic and neuroimmune development are well established. Increasing evidence now suggests that maternal obesity and poor diet can also increase the risk of postpartum mood disorders, but the mechanisms are unknown. Here we investigated the effects of a poor, high-fat-high-sugar diet (HFSD) on p...

The authors would like to correct a typographical error in their recently published paper [...]

Our recent findings indicate that an acute depletion of monocytes has no sustained effects on ovarian follicle health. Here, we utilised a Cx3cr1-Dtr transgenic Wistar rat model to transiently deplete monocytes and investigated the impact of an acute immune challenge by lipopolysaccharide (LPS) on ovarian follicle health and ovulatory capacity rela...

Monocytes and macrophages are the most abundant immune cell populations in the adult ovary, with well-known roles in ovulation and corpus luteum formation and regression. They are activated and proliferate in response to immune challenge and are suppressed by anti-inflammatory treatments. It is also likely they have a functional role in the healthy...

Maternal diet is critical for offspring development and long-term health. Here we investigated the effects of a poor maternal diet pre-conception and during pregnancy on metabolic outcomes and the developing hypothalamus in male and female offspring at birth. We hypothesised that offspring born to dams fed a diet high in fat and sugar (HFSD) peri-p...

Microglia, the key neuroimmune cells of the central nervous system, are best known for their function in defending an individual from pathogens and injury. Recent findings, including our own, suggest microglia also have several immune-independent roles, including in regulating satiety, promoting memory, and modifying pain responses. Many of these m...

Complex organisms rely heavily on intercellular communication. The rapidly expanding field of extracellular vesicle biology has made it clear that the necessary intercellular communication occurs partly through their paracrine and endocrine actions. Extracellular vesicles are nanoscale lipid membranes (30-2000 nm in diameter) that shuttle functiona...

Body composition (the total amount of fat mass, lean mass, minerals and water that constitute the body) is an important measure for understanding an animal’s physiology, ecology and behaviour. Traditional measures of body composition require the animal to either be placed under anaesthetic, which is invasive and can be high-risk, or be euthanised,...

Background: Production of inflammatory mediators by reactive microglial cells in the brain is generally considered the primary mechanism underlying the development of symptoms of sickness in response to systemic inflammation. Methods: Depletion of microglia was achieved in C57BL/6 mice by chronic oral administration of PLX5622, a specific antago...

The Psychoneuroimmunology Research Society (PNIRS) created an official Chinese regional affiliate in 2012, designated PNIRSChina. Now, just eight years later, the program has been so successful in advancing the science of psychoneuroimmunology that it has expanded to the whole of Asia-Oceania. In 2017, PNIRSChina became PNIRSAsia-Pacific. Between 2...

Microglia are resident immune cells of the central nervous system (CNS). In adulthood they are involved in surveillance and responses to pathogens and injury and prenatally they play a role in brain development. However, the role of microglia during the early postnatal period and how they impact development long-term remains poorly understood. Here...

Microglia are resident immune cells of the central nervous system (CNS). In adulthood they are involved in surveillance and responses to pathogens and injury and prenatally they play a role in brain development. However, the role of microglia during the early postnatal period and how they impact development long-term remains poorly understood. Here...

Background: Microglia play a key role in neuronal circuit and synaptic maturation in the developing brain. In the healthy adult, however, their role is less clear: microglial hyperactivation in adults can be detrimental to memory due to excessive synaptic pruning, yet learning and memory can also be impaired in the absence of these cells. In this...

Microglia have been known for decades as key immune cells that shape the central nervous system (CNS) during development and respond to brain pathogens and injury in adult life. Recent findings now suggest that these cells also play a highly complex role in several other functions of the CNS. In this review, we provide a brief overview of the estab...

The early life period is crucially important to how the individual develops, and environmental and lifestyle challenges during this time can lead to lasting programming effects on the brain and immune system. In particular, poor diet in early development can lead to long-term negative metabolic and cognitive outcomes, with those who over-eat in ear...

Background: Production of inflammatory mediators by reactive microglial cells in the brain is generally considered the primary mechanism underlying the development of symptoms of sickness in response to systemic inflammation. Methods: Depletion of microglia was achieved in C57BL/6 mice by chronic oral administration of PLX5622, a specific antagonis...

What happens to your appetite when you are stressed? Do you reach straight for the ice cream and chips? Well, many of us do. With increasing stress in all of our lives, this pattern of stress-related eating can lead to excess weight gain and a higher risk of obesity. But why do we tend to overeat when stressed? One of the biggest culprits may be a...

The early life environment is important in programming brain development, and metabolic disruptions at this time can have long-lasting effects. Previously we have shown that rats that are overfed for the first three weeks of their neonatal life maintain obesity into adulthood. Neonatal overfeeding also leads to primed hypothalamic and hippocampal m...

Chronic stress is a known suppressor of female reproductive function. However, attempts to isolate single causal links between stress and reproductive dysfunction have not yet been successful due to their multi-faceted aetiologies. The gut-derived hormone ghrelin regulates stress and reproductive function and may therefore be pivotal in the neuroen...

The female brain is highly dynamic and can fundamentally remodel throughout the normal ovarian cycle as well as in critical life stages including perinatal development, pregnancy and old-age. As such, females are particularly vulnerable to infections, psychological disorders, certain cancers, and cognitive impairments. We will present the latest ev...

Microglia are one of the primary immune cells of the brain, and are involved in the maintenance of brain health. Microglia are especially important in synaptic pruning and neuronal apoptosis during the early perinatal period. However, the long-term effects of disruptions to this process are not fully understood. We have developed a novel transgenic...

Exposure to stress is a normal and constant facet of life. However, excessive or chronic stress at particular phases of brain development can have lasting detrimental effects on many aspects of physiology, including appetite regulation and metabolism. A specific window of vulnerability to the lasting effects of stress is the early life period, in u...

Ghrelin, an orexigenic gut-derived peptide, is gaining increasing attention due to its multifaceted role in a number of physiological functions, including reproduction. Ghrelin exists in circulation primarily as des-acylated and acylated ghrelin. Des-acyl ghrelin, until recently considered to be an inactive form of ghrelin, is now known to have ind...

Microglia are highly sensitive to dietary influence, becoming activated acutely and long-term by high fat diet. However, their role in regulating satiety and feeding in healthy individuals remains unclear. Here we show that microglia are essential for the normal regulation of satiety and metabolism in rats. Short-term microglial depletion in a Cx3c...

Hippocampal microglia are vulnerable to the effects of aging, displaying a primed phenotype and hyper-responsiveness to various stimuli. We have previously shown that short-term high-fat diet (HFD) significantly impairs hippocampal- and amygdala-based cognitive function in the aged without affecting it in the young. Here, we assessed if morphologic...

Ghrelin, one of the major metabolic hormones involved in controlling energy balance, has recently been shown to have other properties including regulating the hypothalamic-pituitary-adrenal (HPA) axis response to psychological stress and being a potent anti-inflammatory agent. Ghrelin's HPA axis and anti-inflammatory actions have previously been id...

Abstract Background It is well established that lung pathology and inflammation are more severe during respiratory infections complicated by the presence of both bacteria and viruses. Whilst co-infection can result in invasive pneumococcal disease and systemic inflammation, the neuroinflammatory consequences of co-infection are poorly characterised...

The hypothalamus is a key centre for regulation of vital physiological functions, such as appetite, stress responsiveness and reproduction. Development of the different hypothalamic nuclei and its major neuronal populations begins prenatally in both altricial and precocial species, with the fine tuning of neuronal connectivity and attainment of adu...

More than one-third of American adults are obese and statistics are similar worldwide. Caloric intake and diet composition have large and lasting effects on cognition and emotion, especially during critical periods in development, but the neural mechanisms for these effects are not well understood. A clear understanding of the cognitive–emotional p...

Microglia are the primary innate immune cells in the CNS. Since their initial discovery and characterization, decades of research have revealed their unique roles not only in maintaining immune homeostasis, but also being indispensable to brain development and cognitive function. As such, microglia drive synaptogenesis, synaptic pruning, neurogenes...

Previous work, including our own, has shown microglia are highly sensitive to dietary influence, becoming activated acutely and long-term in the presence of high-fat diet or early life overfeeding. Here we investigated if microglia have a direct role in regulating satiety and feeding, using a novel rat model of acute conditional microglial knockout...

Infertility affects 70–80 million couples worldwide. While causes of infertility may include physiological abnormalities, there is clear evidence that chronic stress severely reduces fertility, even in normally-fertile men and women. We have recently discovered that a gut-derived hormone ghrelin may be a pivotal regulator of stress and reproductive...

The early life period is extremely vulnerable to programming effects from the environment, many of which persist into adulthood. We have previously demonstrated that adult rats that were overfed as neonates have hypothalamic microglia that are hyper-responsive to an immune challenge and hippocampal microglia that respond less efficiently to learnin...

Obesity is an increasing problem in young people. Childhood obesity and overweight have increased rapidly on a global scale, and have tripled in the past 30 years, to affect approximately one in five children. Diets high in refined fats and sugar are a major contributor to the development of obesity, and the effects of such obesity-inducing hyperca...

Neonatal overfeeding during the first weeks of life in male rats is associated with a disruption in the peripheral and central leptin systems. Neonatally overfed male rats have increased circulating leptin in the first 2 weeks of life, which corresponds to an increase in body weight compared to normally fed counterparts. These effects are associate...

Early-life stress (ES) is a risk factor for metabolic disorders (e.g. obesity) with a notoriously higher prevalence in women compared to men. However, mechanisms underlying these effects remain elusive. The development of the hypothalamic feeding and metabolic regulatory circuits occurs mostly in the early sensitive postnatal phase in rodents and i...

Infertility affects a remarkable one in four couples in developing countries. Psychological stress is a ubiquitous facet of life, and while stress affects us all at some point, prolonged or unmanageable stress may become harmful for some individuals, negatively impacting on their health, including fertility. For instance, women who struggle to conc...

More Americans are consuming diets higher in saturated fats and refined sugars than ever before, and based on increasing obesity rates, this is a growing trend among older adults as well. While high saturated fat diet (HFD) consumption has been shown to sensitize the inflammatory response to a subsequent immune challenge in young adult rats, the in...

Early life diet influences metabolic programming, increasing the risk for long-lasting metabolic ill-health. Neonatally overfed rats have an early increase in leptin that is maintained long-term and is associated with a corresponding elevation in body weight. However, the immediate and long-term effects of neonatal overfeeding on hypothalamic anore...

Poor white matter development in intrauterine growth restricted (IUGR) babies remains a major, untreated problem in neonatology. New therapies, guided by an understanding of the mechanisms that underlie normal and abnormal oligodendrocyte development and myelin formation, are required. Much of our knowledge of the mechanisms that underlie impaired...

The hypothalamic-pituitary-adrenal (HPA) axis responses to psychological stress are exacerbated in adult female but not male rats made obese due to overfeeding in early life. Ghrelin, traditionally known for its role in energy homeostasis, has been recently recognised for its role in coordinating the HPA responses to stress, particularly by acting...

Rats fed high fat diets have been shown to be impaired in hippocampal-dependent behavioral tasks, such as spatial recognition in the Y-maze and reference memory in the Morris water maze (MWM). It is clear from previous studies, however, that motivation and reward factor into the memory deficits associated with obesity and high-fat diet consumption,...

Since Levine and then Barker's seminal work mid to late last century demonstrating the importance of early life environment, intensive research has revealed the plasticity, vulnerability and resilience of the developing brain to environmental challenges. In particular, early exposure to infectious pathogens and inflammatory stimuli has a lasting im...

Perinatal diet is an important factor in programming brain development and susceptibility to obesity. There are currently several elegant and simple prenatal and postnatal animal models in use to mimic the effects of early life overfeeding and to study its impact on brain and metabolic development. In this chapter we will discuss the background to...

Cover legend: This cover image, by Sarah J. Spencer et al., is based on the Research Article Effects of exercise on adolescent and adult hypothalamic and hippocampal neuroinflammation, DOI: 10.1002/hipo.22620.