Elisa Hill-Yardin

RMIT University | RMIT · School of Health & Biomedical Sciences

Background: Aggression is common in patients with autism spectrum disorders (ASD) along with the core symptoms of impairments in social communication and repetitive behavior. Risperidone, an atypical antipsychotic, is widely used to treat aggression in ASD. In order to understand the neurobiological underpinnings of these challenging behaviors, a...

Gastrointestinal (GI) dysfunction is commonly reported by people diagnosed with autism spectrum disorder (ASD; autism) but the cause is unknown. Mutations in genes encoding synaptic proteins including Neuroligin‐3 are associated with autism. Mice lacking Neuroligin‐3 (Nlgn3−/−) have altered brain function, but whether the enteric nervous system (EN...

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterised by deficits in social communication and restricted or repetitive behaviours. The clinical presentation of ASD is highly variable and diagnosis is based on the presence of impaired social communication and repetitive and/or restricted behaviours. Although the precise patho...

Gastrointestinal (GI) problems constitute an important comorbidity in many patients with autism. Multiple mutations in the neuroligin family of synaptic adhesion molecules are implicated in autism, however whether they are expressed and impact GI function via changes in the enteric nervous system is unknown. We report the GI symptoms of two brother...

Purpose of Review Individuals with autism spectrum disorders (ASD) commonly also suffer from gastrointestinal (GI) dysfunction; however, few animal model studies have systematically examined both ASD and GI dysfunction. In this review, we highlight studies investigating GI dysfunction and alterations in gut microbiota in animal models of ASD with t...

Individuals with autism often experience gastrointestinal issues but the cause is unknown. Many gene mutations that modify neuronal synapse function are associated with autism and therefore may impact the enteric nervous system that regulates gastrointestinal function. A missense mutation in the Nlgn3 gene encoding the cell adhesion protein Neuroli...

Across the globe, approximately one in 10 babies are born preterm, that is, before 37 weeks of a typical 40 weeks of gestation. Up to 50% of preterm born infants develop brain injury, encephalopathy of prematurity (EoP), that substantially increases their risk for developing lifelong defects in motor skills and domains of learning, memory, emotiona...

Enterotoxigenic Escherichia coli (ETEC) is a leading cause of bacterial diarrhea with the potential to cause long-term gastrointestinal (GI) dysfunction. Preventative treatments for ETEC-induced diarrhea exist, yet the effects of these treatments on GI commensals in healthy individuals are unclear. Whether administration of a prophylactic preventat...

Different regions of the gastrointestinal tract have specific functions and thus distinct motility patterns. Motility is primarily regulated by the enteric nervous system (ENS), an intrinsic network of neurons located within the gut wall. Under physiological conditions, the ENS is influenced by the central nervous system (CNS). However, by using ex...

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...

Individuals with autism often experience gastrointestinal issues but the cause is unknown. Many gene mutations that modify neuronal synapse function are associated with autism and therefore may impact the enteric nervous system that regulates gastrointestinal function. A missense mutation in the Nlgn3 gene encoding the cell adhesion protein, Neurol...

Understanding the long-term functional implications of gut microbial communities during the perinatal period is a bourgeoning area of research. Numerous studies have revealed the existence of a “gut-brain axis” and the impact of an alteration of gut microbiota composition in brain diseases. Recent research has highlighted how gut microbiota could a...

Individuals with Autism Spectrum Disorder (ASD; autism) commonly present with gastrointestinal (GI) illness in addition to core diagnostic behavioural traits. The appendix, or cecum in mice, is important for GI homeostasis via its function as a key site for fermentation and a microbial reservoir. Even so, the role of the appendix and cecum in autis...

Maternal influenza A virus (IAV) infection during pregnancy can affect offspring immune programming and development. Offspring born from influenza-infected mothers are of increased risk of neurodevelopmental disorders and have impaired respiratory mucosal immunity against pathogens. The gut-associated lymphoid tissue (GALT) represents a large propo...

Mutations in the Neuroligin-3 (Nlgn3) gene are implicated in autism spectrum disorder (ASD) and gastrointestinal (GI) dysfunction, but cellular Nlgn3 expression in the enteric nervous system remains to be characterised. We combined RNAScope in situ hybridization and immunofluorescence to measure Nlgn3 mRNA expression in cholinergic and VIP-expressi...

Mutations in the Neuroligin-3 (Nlgn3) gene are implicated in autism spectrum disorder (ASD) and gastrointestinal (GI) dysfunction but cellular Nlgn3 expression in the enteric nervous system remains to be characterised. We combined RNAScope in situ hybridization for Nlgn3 mRNA and immunofluorescence for cholinergic and VIP-expressing submucosal neur...

Individuals with Autism Spectrum Disorder (ASD; autism) commonly present with gastrointestinal (GI) illness in addition to core diagnostic behavioural traits. The appendix, or cecum in mice, is important for GI homeostasis via its function as a key site for fermentation and a microbial reservoir. Even so, the role of the appendix and cecum in autis...

Increasingly, the interface of the nervous system and bacteria is being investigated with respect to wellbeing, given that the communications between the gut and the brain are recognized to be integral in health and disease. In this topic, the microbial profiles were studied in relation to behavioural changes, genetic and environmental influences,...

Cerebral malaria (CM) is the most severe form of malaria with the highest mortality rate and can result in life-long neurological deficits and ongoing comorbidities. Factors contributing to severity of infection and development of CM are not fully elucidated. Recent studies have indicated a key role of the gut microbiome in a range of health condit...

Autism spectrum disorder (ASD; autism) is a prevalent neurodevelopmental disorder associated with changes in gut-brain axis communication. Gastrointestinal (GI) symptoms are experienced by a large proportion of individuals diagnosed with autism. Several mutations associated with autism modify cellular communication via neuronal synapses. It has bee...

Surgical site infections (SSI) are among the most common medical infections, occurring in 2 to 4% of patients undergoing a surgical procedure. Smart surgical sutures can play an important role in preventing infection. For example, antimicrobial sutures detectable via clinical imaging modalities can support monitoring wounds post-surgery and enhance...

Individuals diagnosed with neurodevelopmental conditions such as autism spectrum disorder (ASD; autism) often experience tissue inflammation as well as gastrointestinal dysfunction, yet their underlying causes remain poorly characterised. Notably, the largest components of the body’s immune system, including gut-associated lymphoid tissue (GALT), l...

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...

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with a history of repetitive head impacts (RHI). CTE was described in boxers as early as the 1920s and by the 1950s it was widely accepted that hits to the head caused some boxers to become “punch drunk.” However, the recent discovery of CTE in American and Australian-...

Many individuals diagnosed with autism spectrum disorder (ASD) experience gastrointestinal (GI) dysfunction and show microbial dysbiosis. Variation in gut microbial populations is associated with increased risk for GI symptoms such as chronic constipation and diarrhoea, which decrease quality of life. Several preclinical models of autism also demon...

The intestinal mucus layer protects the host from invading pathogens and is essential for maintaining a healthy mucosal microbial community. Alterations in the mucus layer and composition of mucus-residing microbiota in people diagnosed with Autism Spectrum Disorder (ASD; autism) may contribute to dysbiosis and gastrointestinal (GI) dysfunction. Al...

The mouse caecum is a pouch-like structure that is anatomically similar to the human appendix and is hypothesised to serve as a reservoir for commensal bacteria. The gastrointestinal tract is also home to the largest immunological organ of the body and the enteric nervous system (ENS), which regulates gut motility and secretion. The caecum is there...

Mutations in the Neuroligin-3 (Nlgn3) gene are implicated in autism spectrum disorder (ASD) and gastrointestinal (GI) dysfunction but its cellular expression in the GI tract remains to be characterised. Localisation of NLGN3 protein is challenging in intestinal tissue due to the lack of target-specific antibodies. Here, we combined RNAScope in situ...

Enterotoxigenic Escherichia coli (ETEC) is a leading cause of bacterial diarrhea in travelers, military personnel and children in developing countries. Infection has the potential to cause long-term gastrointestinal dysfunction. Preventative treatments for ETEC-induced diarrhea exist, yet the effects of these treatments on gastrointestinal commensa...

Women are more susceptible to functional bowel disorders than men and the severity of their symptoms such as diarrhea, constipation, abdominal pain and bloating changes over the menstrual cycle, suggesting a role for sex hormones in gastrointestinal function. Nitric oxide (NO) is a major inhibitory neurotransmitter in the gut and blockade of nitric...

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...

Purpose of Review Mild traumatic brain injury (mTBI) is a continuing healthcare concern worldwide contributing to significant cognitive and neurological impairment, consequently affecting activities of daily living. While mTBI recovery is becoming well studied, there are no interventions to reduce the known impairments of mTBI. Omega-3 fatty acids...

Editorial on the Research Topic Interactions of the Nervous System With Bacteria

Emerging evidence of brain injury on risk of neurodegenerative diseases such as Alzheimer’s disease (AD) and chronic traumatic encephalopathy (CTE) have resulted in interest in therapeutic potential of omega-3 fatty acids (n-3FA). We conducted a systematic review of n-3FA therapeutic efficacy for ageing adults at risk of AD/CTE following a history...

Abstract Foetus sterility until parturition is under debate due to reports of microorganisms in the foetal environment and meconium. Sufficient controls to overcome sample contamination and provide direct evidence of microorganism viability in the pre-rectal gastrointestinal tract (GIT) have been lacking. We conducted molecular and culture-based an...

Autism Spectrum Disorder (ASD; autism) is a neurodevelopmental disorder characterised by deficits in social communication, and restricted and/or repetitive behaviours. While the precise pathophysiologies are unclear, increasing evidence supports a role for dysregulated neuroinflammation in the brain with potential effects on synapse function. Here,...

Gastrointestinal (GI) dysfunction is a common comorbidity of autism spectrum disorders (ASD) and is associated with increased severity of characteristic autism-associated symptoms. However, the underlying biological mechanisms for GI dysfunction symptoms in children with ASD are unknown. This review explores potential explanations for these symptom...

Mucus is integral to gut health and its properties may be affected in neurological disease. Mucus comprises a hydrated network of polymers including glycosylated mucin proteins. We propose that factors that influence the nervous system may also affect the volume, viscosity, porosity of mucus composition and subsequently, gastrointestinal (GI) micro...

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterised by impairments in social communication and the presence of restrictive and repetitive behaviours. A mouse model expressing an autism-associated R451C mutation in the gene encoding the synaptic adhesion protein neuroligin-3 (NL3) has been extensively characterised and show...

Interactions between the gut microbiome and the brain affect mood and behaviour in health and disease. Using preclinical animal models, recent discoveries begin to explain how bacteria in the gut affect our mood as well as highlighting new findings relevant to autism. Autism-associated gene mutations known to affect synapse function in the CNS also...

The intrinsic nervous system of the gut interacts with the gut-associated lymphoid tissue (GALT) via bidirectional neuroimmune interactions. The caecum is an understudied region of the gastrointestinal (GI) tract that houses a large supply of microbes and is involved in generating immune responses. The caecal patch is a lymphoid aggregate located w...

Background: Autism Spectrum Disorder (ASD) symptoms are commonly treated with a variety of pharmaceuticals which can have adverse side effects. A study of pharmacogenetic biomarkers for ASD medications and association with gastrointestinal (GI) dysfunction symptoms was conducted in individuals diagnosed with autism and/or GI dysfunction to provide...

This study investigated genetic biomarkers for gastrointestinal dysfunction symptoms in order to provide further information on the genetic risk for GI dysfunction associated with autism. The single nucleotide polymorphisms of sixty participants with autism and/or gastrointestinal dysfunction were analyzed. The autism group had a moderate statistic...

Gestational diabetes mellitus (GDM) is a common pregnancy complication, particularly prevalent in obese women. Importantly, exercise has beneficial impacts on maternal glucose control and may prevent GDM in “at‐risk” women. We aimed to determine whether a high‐fat diet (HFD) exacerbates metabolic dysfunction and alters gut microbiome in GDM and whe...

Background/aims: Patients with Duchenne muscular dystrophy exhibit significant, ongoing impairments in gastrointestinal (GI) function likely resulting from dysregulated nitric oxide production. Compounds increasing neuronal nitric oxide synthase expression and/or activity could improve GI dysfunction and enhance quality of life for dystrophic pati...

Glutamate is a classic excitatory neurotransmitter in the central nervous system (CNS), but despite several studies reporting the expression of glutamate together with its various receptors and transporters within the enteric nervous system (ENS), its role in the gut remains elusive. In this study, we characterized the expression of the vesicular g...

Understanding neuronal mechanisms underlying aggression in patients with autism spectrum disorder (ASD) could lead to better treatments and prognosis. The Neuroligin-3 (NL3)R451C mouse model of ASD has a heightened aggressive phenotype, however the biological mechanisms underlying this behavior are unknown. It is well established that NL3R451C mice...

Genetic factors might be largely responsible for the development of autism spectrum disorder (ASD) that alone or in combination with specific environmental risk factors trigger the pathology. Multiple mutations identified in ASD patients that impair synaptic function in the central nervous system are well studied in animal models. How these mutatio...

The antiepileptic drug phenytoin (PHT) is thought to reduce the excitability of neural tissue by stabilizing sodium channels (NaV) in inactivated states. It has been suggested the fast-inactivated state (IF) is the main target, although slow inactivation (IS) has also been implicated. Other studies on local anesthetics with similar effects on sodiu...

Objective: Fracture risk is a serious comorbidity in epilepsy and may relate to the use of antiepileptic drugs (AEDs). Many AEDs inhibit ion channel function, and the expression of these channels in osteoblasts raises the question of whether altered bone signaling increases bone fragility. We aimed to confirm the expression of voltage-gated sodium...

Key points: Cholera causes more than 100,000 deaths each year as a result of severe diarrhoea, vomiting and dehydration due to the actions of cholera toxin; more females than males are affected. Cholera toxin induces hypersecretion via release of mucosal serotonin and over-activation of enteric neurons, but its effects on gastrointestinal motility...

The enteric nervous system (ENS) plays an important role in regulating gastrointestinal (GI) motility and can function independently of the central nervous system. Changes in ENS function are a major cause of GI symptoms and disease and may contribute to GI symptoms reported in neuropsychiatric disorders including autism. It is well established tha...

Epileptic encephalopathies, including Dravet syndrome, are severe treatment-resistant epilepsies with developmental regression. We examined a mouse model based on a human β1 sodium channel subunit (Scn1a) mutation. Homozygous mutant mice shared phenotypic features and pharmaco-sensitivity with Dravet syndrome. Patch-clamp analysis showed that mutan...

Environmental enrichment (EE) has been shown to induce beneficial effects in mouse models of autism spectrum disorder (ASD), as well as animal models of a variety of other neurological and psychiatric disorders. Investigation of the mechanisms responsible for these changes in animal models will facilitate translation of EE and associated therapies...

Autism spectrum disorder (ASD) patients commonly exhibit a variety of comorbid traits including seizures, anxiety, aggressive behavior, gastrointestinal problems, motor deficits, abnormal sensory processing, and sleep disturbances for which the cause is unknown. These features impact negatively on daily life and can exaggerate the effects of the co...

The cannabinoid receptor CB1 is found in abundance in brain neurons, whereas CB2 is essentially expressed outside the brain. In the neocortex, CB1 is observed predominantly on large cholecystokinin (CCK) expressing interneurons. However, physiological evidence suggests that functional CB1 are present on other neocortical neuronal types, including p...

The deeper part of neocortical layer VI is dominated by nonpyramidal neurons, which lack a prominent vertically ascending dendrite and predominantly establish corticocortical connections. These neurons were studied in rat neocortical slices using patch-clamp, single-cell reverse transcription-polymerase chain reaction, and biocytin labeling. The ma...

A missense mutation (R43Q) in the γ2 subunit of the γ-aminobutyric acid (GABA)(A) receptor is associated with generalized (genetic) epilepsy with febrile seizures plus (GEFS+). Heterozygous GABA(A) γ2(R43Q) mice displayed a lower temperature threshold for thermal seizures as compared to wild-type littermates. Temperature-dependent internalization o...

Febrile seizures are a common childhood seizure disorder and a defining feature of genetic epilepsy with febrile seizures plus (GEFS+), a syndrome frequently associated with Na+ channel mutations. Here, we describe the creation of a knockin mouse heterozygous for the C121W mutation of the beta1 Na+ channel accessory subunit seen in patients with GE...

The deeper part of neocortical layer VI is dominated by nonpyramidal neurons, which lack a prominent vertically ascending dendrite and predominantly establish corticocortical connections. These neurons were studied in rat neocortical slices using patch-clamp, single-cell reverse transcription-polymerase chain reaction, and biocytin labeling. The ma...

We studied mu-opioid transmission in acute slices of rat neocortex using whole-cell recordings and single-cell reverse transcription-polymerase chain reaction. The mu-opioid receptor (MOR) was found in gamma-aminobutyric acidergic (GABAergic) interneurons that were either layer I cells frequently expressing neuropeptide Y or layers II-V cells expre...

The cannabinoid receptor CB1 is found in abundance in brain neurons, whereas CB2 is essentially expressed outside the brain. In the neocortex, CB1 is observed predominantly on large cholecystokinin (CCK)-expressing interneurons. However, physiological evidence suggests that functional CB1 are present on other neocortical neuronal types. We investig...

Neocortical neurons expressing the serotonin 5-HT3 receptor (5-HT3R) were characterized in rat acute slices by using patch-clamp recordings combined with single-cell RT-PCR and histochemical labeling. The 5-HT3A receptor subunit was expressed selectively in a subset of GABAergic interneurons coexpressing cholecystokinin (CCK) and vasoactive intesti...

Cortical cells were classified using an unsupervised cluster analysis based upon their quantitative and combinatorial immunoreactivity for glutamate, gamma-aminobutyric acid (GABA), aspartate, glutamine and taurine. Overall, cell class-specific amino acid signatures were found for 12 cellular types; seven GABA-immunoreactive (GABA-IR) populations (...

Glutamate is an important amino acid in the neocortex for metabolic and neurotransmitter functions. The objective of this study was to detect variations in cellular glutamate content using quantitative immunocytochemistry. We show that glutamate is present in almost all cortical cells and coexists with other amino acids such as aspartate, glutamine...