Alzheimer's disease research progress in Australia: The Alzheimer's Association International Conference Satellite Symposium in Sydney.

The Alzheimer's Association International Conference held its sixth Satellite Symposium in Sydney, Australia in 2019, highlighting the leadership of Australian researchers in advancing the understanding of and treatment developments for Alzheimer's disease (AD) and other dementias. This leadership includes the Australian Imaging, Biomarker, and Lifestyle Flagship Study of Ageing (AIBL), which has fueled the identification and development of many biomarkers and novel therapeutics. Two multimodal lifestyle intervention studies have been launched in Australia; and Australian researchers have played leadership roles in other global studies in diverse populations. Australian researchers have also played an instrumental role in efforts to understand mechanisms underlying vascular contributions to cognitive impairment and dementia; and through the Women's Healthy Aging Project have elucidated hormonal and other factors that contribute to the increased risk of AD in women. Alleviating the behavioral and psychological symptoms of dementia has also been a strong research and clinical focus in Australia.

Exogenous corticosterone reduces L-DOPA-induced dyskinesia in the hemi-parkinsonian rat: role for interleukin-1beta.

While the etiology of Parkinson's disease (PD) remains unknown, there is overwhelming evidence that neuroinflammation plays a critical role in the progressive loss of dopamine (DA) neurons. Because nearly all persons suffering from PD receive l-DOPA, it is surprising that inflammation has not been examined as a potential contributor to the abnormal involuntary movements (AIMs) that occur as a consequence of chronic l-DOPA treatment. As an initial test of this hypothesis, we examined the effects of exogenously administered corticosterone (CORT), an endogenous anti-inflammatory agent, on the expression and development of l-DOPA-induced dyskinesia (LID) in unilateral DA-depleted rats. To do this, male Sprague-Dawley rats received unilateral medial forebrain bundle 6-hydroxydopamine lesions. Three weeks later, l-DOPA primed rats received acute injections of CORT (0-3.75 mg/kg) prior to l-DOPA to assess the expression of LID. A second group of rats was used to examine the development of LID in l-DOPA naïve rats co-treated with CORT and l-DOPA for 2 weeks. AIMs and rotations were recorded. Exogenous CORT dose-dependently attenuated both the expression and development of AIMs without affecting rotations. Real-time reverse-transcription polymerase chain reaction of striatal tissue implicated a role for interleukin-1 (IL-1) beta in these effects as its expression was increased on the lesioned side in rats treated with l-DOPA (within the DA-depleted striatum) and attenuated with CORT. In the final experiment, interleukin-1 receptor antagonist (IL-1ra) was microinjected into the striatum of l-DOPA-primed rats to assess the impact of IL-1 signaling on LID. Intrastriatal IL-1ra reduced the expression of LID without affecting rotations. These findings indicate a novel role for neuroinflammation in the expression of LID, and may implicate the use of anti-inflammatory agents as a potential adjunctive therapy for the treatment of LID.

Adaptation in the corticosterone and hyperthermic responses to stress following repeated stressor exposure.

Previous studies have shown that repeated daily exposure to the same (homotypic) stressor results in habituation of the corticosterone (CORT) response. Others have found that the stress response to a more ethologically relevant stressor, social defeat, does not habituate and, in some cases, sensitisation has been observed. Similar observations have been noted when core temperature is examined. Although habituation and/or sensitisation have been reported during stressor exposure, little is known about the development of an anticipatory fever in response to daily stressor exposure. The aim of the present study was to compare systematically commonly used laboratory stressors (i.e. restraint, cage confinement and social defeat) using a common set of procedures and analyses. Specifically, we examined: (i) the development of an anticipatory fever to repeated (5 days) homotypic stressor exposure; (ii) the adaptation of the fever response during stressor exposure; and (iii) the resolution of the fever response to stressors presented at the same time each day. For comparison, adaptation of the CORT response was also examined to assess the degree to which habituation to repeated stressor exposure may represent a more general response observed across diverse physiological measures. Habituation was observed after restraint and cage confinement, but not observed in either the CORT or hyperthermic responses to repeated social defeat. Furthermore, no anticipatory fever response was observed with repeated exposure to restraint, cage confinement, or social defeat. These data suggest that habituation to repeated stressor exposure may not occur with all homotypic stressor paradigms. In addition, rats do not appear to entrain an anticipatory fever response to a stressor presented at the same time each day, at least not within 5-6 days of repeated exposure.