title: Neuromolecular basis of anomalous feeding behaviour in the valproate rat model of autism

authors: Pal, Tapasya

subjects: Valproate rat model of autism

abstract: Autism spectrum disorder (ASD), which affects circa 1% of the global population, is characterized by impairments in social communication, interaction, language disability, sensory anomalies, repetitive behaviours, and intellectual disability. Aberrant feeding behaviour is a common comorbidity of ASD. ASD individuals often demonstrate extreme food selectivity, refusal, dependence on few very particular food items, neophobia etc. which can lead to nutritional deficiencies affecting development. However, the underlying neurophysiological mechanisms of aberrant food intake in ASD are not well known.

Prenatal exposure to the antiepileptic drug, valproic acid (VPA), leads to autism. The prenatally VPA-exposed rats are model organisms to study ASD and they show ASD-like symptoms of, among others, elevated anxiety and decreased social interaction. Importantly, very little is known about appetite control in these animals. The overall goal of the studies included in this thesis was to identify potential feeding behavioural anomalies and associated neuromolecular changes in the VPA rat model of ASD. We thus hypothesize that ASD is associated with abnormal appetite and reward-driven feeding.

The key factors shaping consumption involve hunger (determines search for calories), satiation (underpins termination of feeding) and reward (consumption for the 'pleasantness' of food, regardless of the energy requirements). Thus, in the first Specific Aim of this thesis, the hunger processing in the VPA animals was investigated. The ad libitum intake of ‘bland’ standard laboratory chow was assessed in VPA versus non-VPA controls maintained continuously on this diet. The adult VPA rats ate less ‘bland’ chow than healthy controls did, and it was coupled with a moderately lower body weight than that of the controls. VPA rats also ate less of the standard chow after acute food deprivation. There was an aberrant change in c-Fos immunoreactivity in key brain sites that govern food intake, including the hypothalamic and brain stem areas, in the VPA animals in contrast to the healthy controls upon food deprivation, which indicates differences in neural processing of hunger in autism. This finding is further supported by a lack of change in expression patterns of feeding-related genes

(including oxytocin (OT), Agouti-related protein (AgRP) and mu opioid receptor (MOR)) upon hunger in the hypothalamus in the VPAs as opposed to the controls. Cumulatively, these findings suggest that hunger processing is altered in the VPA rats.

In the second Specific Aim of this project, intake of rewarding diets in the VPA rats was examined to address whether ASD affects pleasure-driven consumption. In episodic meal consumption paradigms, i.e., in scenarios in which energy non-deprived animals were given a brief and non-habitual access to diets that differ in palatability, the VPA rats were found to consume elevated amounts of tasty liquid and solid diets. These data suggest that VPA rats display not only altered energy homeostatis processing (as shown in Specific Aim 1), but also indicate changes in the regulation of eating for palatability.

Considering the abnormal OT signalling in autism and the fact that OT decreases feeding for energy and feeding for palatability, the third Specific Aim addressed whether VPA rats exhibit heightened sensitivity to exogenously administered OT, a peptide known for its anorexigenic properties. Intraperitoneal OT treatment was found to reduce episodic intake of palatable diets as well as post-energy deprivation intake of ‘bland’ chow; however, the dose needed to generate hypophagia was lower in VPAs than in controls. c-Fos immunohistochemistry revealed that the lower OT dose found to be anorexigenic in VPA rats, was sufficient to affect brain activation in a manner typical for hypophagia, whereas in healthy control rats, it did not induce significant c-Fos changes.

Importantly, OT is involved also in the process of avoidance of toxic foods, i.e., it facilitates the development of a conditioned taste aversion (CTA). Therefore, the goal of the Specific Aim 4, was to assess whether VPA animals display atypical taste aversion acquisition. It was found that VPAs failed to develop aversion to a standard dose of LiCl that induces a CTA in healthy non-ASD controls. In line with the outcome of the behavioural study, the immunohistochemical analysis revealed lower c-Fos-OT colocalization in the PVN in VPAs and a less pronounced broader CTA circuit c-Fos response in ASD animals compared to controls after LiCl treatment.

Taken together, evidence presented in this thesis shows that ASD is associated with abnormal appetite in VPA rats and it offers an insight into the neural basis of this phenomenon. The VPA animals show a slight decrease in intake of standard ‘bland’ chow, an elevated drive to consume palatable tastants, and resistance to taste aversion. These anomalies in feeding behaviours are underpinned by distinct changes in brain activation and gene expression patterns, as well as altered sensitivity to anorexigenic properties of OT, a neuropeptide known to affect other symptoms of ASD, from social deficits to anxiety.

text: Neuromolecular basis of anomalous feeding behaviour in the valproate rat model of autism Autism spectrum disorder (ASD), which affects circa 1% of the global population, is characterized by impairments in social communication, interaction, language disability, sensory anomalies, repetitive behaviours, and intellectual disability. Aberrant feeding behaviour is a common comorbidity of ASD. ASD individuals often demonstrate extreme food selectivity, refusal, dependence on few very particular food items, neophobia etc. which can lead to nutritional deficiencies affecting development. However, the underlying neurophysiological mechanisms of aberrant food intake in ASD are not well known.

Prenatal exposure to the antiepileptic drug, valproic acid (VPA), leads to autism. The prenatally VPA-exposed rats are model organisms to study ASD and they show ASD-like symptoms of, among others, elevated anxiety and decreased social interaction. Importantly, very little is known about appetite control in these animals. The overall goal of the studies included in this thesis was to identify potential feeding behavioural anomalies and associated neuromolecular changes in the VPA rat model of ASD. We thus hypothesize that ASD is associated with abnormal appetite and reward-driven feeding.

The key factors shaping consumption involve hunger (determines search for calories), satiation (underpins termination of feeding) and reward (consumption for the 'pleasantness' of food, regardless of the energy requirements). Thus, in the first Specific Aim of this thesis, the hunger processing in the VPA animals was investigated. The ad libitum intake of ‘bland’ standard laboratory chow was assessed in VPA versus non-VPA controls maintained continuously on this diet. The adult VPA rats ate less ‘bland’ chow than healthy controls did, and it was coupled with a moderately lower body weight than that of the controls. VPA rats also ate less of the standard chow after acute food deprivation. There was an aberrant change in c-Fos immunoreactivity in key brain sites that govern food intake, including the hypothalamic and brain stem areas, in the VPA animals in contrast to the healthy controls upon food deprivation, which indicates differences in neural processing of hunger in autism. This finding is further supported by a lack of change in expression patterns of feeding-related genes

(including oxytocin (OT), Agouti-related protein (AgRP) and mu opioid receptor (MOR)) upon hunger in the hypothalamus in the VPAs as opposed to the controls. Cumulatively, these findings suggest that hunger processing is altered in the VPA rats.

In the second Specific Aim of this project, intake of rewarding diets in the VPA rats was examined to address whether ASD affects pleasure-driven consumption. In episodic meal consumption paradigms, i.e., in scenarios in which energy non-deprived animals were given a brief and non-habitual access to diets that differ in palatability, the VPA rats were found to consume elevated amounts of tasty liquid and solid diets. These data suggest that VPA rats display not only altered energy homeostatis processing (as shown in Specific Aim 1), but also indicate changes in the regulation of eating for palatability.

Considering the abnormal OT signalling in autism and the fact that OT decreases feeding for energy and feeding for palatability, the third Specific Aim addressed whether VPA rats exhibit heightened sensitivity to exogenously administered OT, a peptide known for its anorexigenic properties. Intraperitoneal OT treatment was found to reduce episodic intake of palatable diets as well as post-energy deprivation intake of ‘bland’ chow; however, the dose needed to generate hypophagia was lower in VPAs than in controls. c-Fos immunohistochemistry revealed that the lower OT dose found to be anorexigenic in VPA rats, was sufficient to affect brain activation in a manner typical for hypophagia, whereas in healthy control rats, it did not induce significant c-Fos changes.

Importantly, OT is involved also in the process of avoidance of toxic foods, i.e., it facilitates the development of a conditioned taste aversion (CTA). Therefore, the goal of the Specific Aim 4, was to assess whether VPA animals display atypical taste aversion acquisition. It was found that VPAs failed to develop aversion to a standard dose of LiCl that induces a CTA in healthy non-ASD controls. In line with the outcome of the behavioural study, the immunohistochemical analysis revealed lower c-Fos-OT colocalization in the PVN in VPAs and a less pronounced broader CTA circuit c-Fos response in ASD animals compared to controls after LiCl treatment.

Taken together, evidence presented in this thesis shows that ASD is associated with abnormal appetite in VPA rats and it offers an insight into the neural basis of this phenomenon. The VPA animals show a slight decrease in intake of standard ‘bland’ chow, an elevated drive to consume palatable tastants, and resistance to taste aversion. These anomalies in feeding behaviours are underpinned by distinct changes in brain activation and gene expression patterns, as well as altered sensitivity to anorexigenic properties of OT, a neuropeptide known to affect other symptoms of ASD, from social deficits to anxiety.

year: 2023

title: The uptake of artificial roosts by long-tailed bats (Chalinolobus tuberculatus) in Hamilton City

authors: Robinson, Hannah Lois

subjects: Long-tailed bat

abstract: Globally, short to medium-term mitigation for the loss of bat roosting habitat has largely favoured the implementation of artificial roosts. However, their implementation has somewhat outpaced research, resulting in highly generalised guidelines concerning installation, maintenance, and reported suitability. Large-scale infrastructure and urban development projects in New Zealand are increasingly occurring in recognised long-tailed bat (Chalinolobus tuberculatus) habitat. In 2019, to provide mitigation for the Southern Links Roading Project, 80 artificial roosts were installed in urban parks within Hamilton City. To better understand the uptake and suitability of artificial roosts for long-tailed bats. Research objectives included determination of artificial roost uptake and identification of specific areas of occupation or seasonal differences in occupation. In addition, seasonal acoustic bat surveys and mammalian predator surveys were conducted in ten locations within the vicinity of artificial roosts to determine their potential influence on roost uptake. Habitat surveys and geospatial analyses were also undertaken to understand what factors are important for artificial roost occupation, and if those factors can be used to reliably predict the probability of occupation. Twenty-four (31%) of the 76 monitored artificial roosts were observed as occupied by long-tailed bats. Occupation was largely infrequent, with no clear seasonal difference, or specific areas of occupation. Two triple-chambered boxes installed in 2012 in Sandford Park-A were the exception, with the number of roosting bats notably increasing over the summer maternity season. Areas with comparatively high bat activity (>50 bat passes/night) corresponded with a greater percentage of occupied artificial roosts. The prevalence of mammalian predators in urban parks connected to the Mangakotukuku Gully, was comparatively high with 50% of the chew track cards damaged by rats and possums each month, and at least one possum pass was recorded by camera traps per survey night. However, predator prevalence appeared to have little influence on artificial roost uptake due to the anti-predator bands on trees. General linear modelling indicated positive probability of roost occupation with increasing distance to stand edge, high canopy cover, and increasing terrain slope. This indicated that Hamilton City long-tailed bats prefer sheltered artificial roosts, installed further from the stand edge within landscape features such as gullies. The logistic model also identified that distance to stand edge was the only variable that could be used to reliably predict roost occupation. Positive probability of roost occupation with an increasing number of chambers indicated that bats prefer multichambered roosts that facilitate clustering, and the provision of a range of microclimatic conditions within the roost. Negative probability of roost occupation as distance to occupied roosts increased indicated that bats may prefer to roost in clusters of artificial roosts. Future artificial roost installation in Hamilton City should situate roosts in sheltered locations, ideally nearby natural or already occupied artificial roosts to facilitate discovery and uptake. Prior to installation, bat activity should be monitored so box installation can prioritise areas with high activity. Anti-predator band maintenance should also occur at least every 6-months to ensure bands have not detached, which may place roosting bats at risk of predation.

text: The uptake of artificial roosts by long-tailed bats (Chalinolobus tuberculatus) in Hamilton City Globally, short to medium-term mitigation for the loss of bat roosting habitat has largely favoured the implementation of artificial roosts. However, their implementation has somewhat outpaced research, resulting in highly generalised guidelines concerning installation, maintenance, and reported suitability. Large-scale infrastructure and urban development projects in New Zealand are increasingly occurring in recognised long-tailed bat (Chalinolobus tuberculatus) habitat. In 2019, to provide mitigation for the Southern Links Roading Project, 80 artificial roosts were installed in urban parks within Hamilton City. To better understand the uptake and suitability of artificial roosts for long-tailed bats. Research objectives included determination of artificial roost uptake and identification of specific areas of occupation or seasonal differences in occupation. In addition, seasonal acoustic bat surveys and mammalian predator surveys were conducted in ten locations within the vicinity of artificial roosts to determine their potential influence on roost uptake. Habitat surveys and geospatial analyses were also undertaken to understand what factors are important for artificial roost occupation, and if those factors can be used to reliably predict the probability of occupation. Twenty-four (31%) of the 76 monitored artificial roosts were observed as occupied by long-tailed bats. Occupation was largely infrequent, with no clear seasonal difference, or specific areas of occupation. Two triple-chambered boxes installed in 2012 in Sandford Park-A were the exception, with the number of roosting bats notably increasing over the summer maternity season. Areas with comparatively high bat activity (>50 bat passes/night) corresponded with a greater percentage of occupied artificial roosts. The prevalence of mammalian predators in urban parks connected to the Mangakotukuku Gully, was comparatively high with 50% of the chew track cards damaged by rats and possums each month, and at least one possum pass was recorded by camera traps per survey night. However, predator prevalence appeared to have little influence on artificial roost uptake due to the anti-predator bands on trees. General linear modelling indicated positive probability of roost occupation with increasing distance to stand edge, high canopy cover, and increasing terrain slope. This indicated that Hamilton City long-tailed bats prefer sheltered artificial roosts, installed further from the stand edge within landscape features such as gullies. The logistic model also identified that distance to stand edge was the only variable that could be used to reliably predict roost occupation. Positive probability of roost occupation with an increasing number of chambers indicated that bats prefer multichambered roosts that facilitate clustering, and the provision of a range of microclimatic conditions within the roost. Negative probability of roost occupation as distance to occupied roosts increased indicated that bats may prefer to roost in clusters of artificial roosts. Future artificial roost installation in Hamilton City should situate roosts in sheltered locations, ideally nearby natural or already occupied artificial roosts to facilitate discovery and uptake. Prior to installation, bat activity should be monitored so box installation can prioritise areas with high activity. Anti-predator band maintenance should also occur at least every 6-months to ensure bands have not detached, which may place roosting bats at risk of predation.

year: 2022

title: He Pikinga Waiora Kimi Ora lifestyle programme: Case study of a successful community-based indigenous diabetes intervention

authors: Masters-Awatere, Bridgette

subjects: adult

abstract: AIM: To co-design and implement a whānau-centred, community-based lifestyle programme (Kimi Ora) intended to ensure no worsening of HbA1c and to improve wellbeing for Māori whānau and communities with diabetes or pre-diabetes. 

METHODS: Māori healthcare providers, community members, research advisors and wider stakeholders used a co-design process underpinned by He Pikinga Waiora to collaboratively develop and implement Kimi Ora Control group comparisons and participants were recruited from Te Kōhao Health. Multi-method monitoring and collection captured individual, whānau and community data. 

RESULTS: Kimi Ora was run in two communities in Aotearoa New Zealand. In total, there were 35 participants who took part in an eight-week programme offered five times alongside a comparison group comprising 21 participants. Kimi Ora resulted in significant improvements on all biomedical measures compared to baseline, and participants had gains relative to the comparison group for variables including weight, BMI, blood pressure and waist measurement. Of particular note was the 100% retention rate and sustained community support for Kimi Ora.

CONCLUSIONS: Outcomes from Kimi Ora demonstrate this programme, which was actively tailored for and worked with Māori communities in a responsive and flexible manner, resulted in successful biomedical outcomes, high engagement and high retention.

text: He Pikinga Waiora Kimi Ora lifestyle programme: Case study of a successful community-based indigenous diabetes intervention AIM: To co-design and implement a whānau-centred, community-based lifestyle programme (Kimi Ora) intended to ensure no worsening of HbA1c and to improve wellbeing for Māori whānau and communities with diabetes or pre-diabetes. 

METHODS: Māori healthcare providers, community members, research advisors and wider stakeholders used a co-design process underpinned by He Pikinga Waiora to collaboratively develop and implement Kimi Ora Control group comparisons and participants were recruited from Te Kōhao Health. Multi-method monitoring and collection captured individual, whānau and community data. 

RESULTS: Kimi Ora was run in two communities in Aotearoa New Zealand. In total, there were 35 participants who took part in an eight-week programme offered five times alongside a comparison group comprising 21 participants. Kimi Ora resulted in significant improvements on all biomedical measures compared to baseline, and participants had gains relative to the comparison group for variables including weight, BMI, blood pressure and waist measurement. Of particular note was the 100% retention rate and sustained community support for Kimi Ora.

CONCLUSIONS: Outcomes from Kimi Ora demonstrate this programme, which was actively tailored for and worked with Māori communities in a responsive and flexible manner, resulted in successful biomedical outcomes, high engagement and high retention.

year: 2021