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PNIRS 2024 Member Sponsored SymposiaMember Sponsored Symposia 1 & 2 -- Monday, June 24, 4:00 - 5:30 pm 1. Dietary Diversity and What it Means for Old Age This member-sponsored symposium will highlight three speakers from our international European Union Joint Program on Neurodegenerative disease-funded consortium, Effects of early-Stress On Lipid mediators and Inflammation for early Detection of neurodegeneration “SOLID”. This consortium is made up of 7 Partner Investigators (PIs) and 6 other External Collaborator team leaders. We are nominating three of the PIs to showcase our research. Alzheimer’s Disease (AD), dementia, and cognitive dysfunction affect more than 50 million people worldwide. With our aging population the absolute numbers of those affected will explode in coming years. 95% of AD is sporadic and the aetiology is unknown and not adequately explained by genetics. So, what makes some of us susceptible and some vulnerable? This symposium will address how differences in dietary background can lead to early neuroinflammation in some individuals and this inflammatory background then dictates the risk of AD, dementia and cognitive dysfunction. In addition to the science, our symposium will also demonstrate novel collaborative approaches to attracting funding from international sources. It will also highlight an important success story in the networking opportunities afforded by engagement with PNIRS. This SOLID collaboration was forged from introductions made at the Brighton PNIRS meeting in 2016 between 3 of the PIs that has led to long-term collaborations, broader collaborative networks, shared funding, co-tutelle PhD agreements, shared publications, and lasting friendships. 2. Microglial Regulation of Sex-Specific Neural Development As the primary innate immune cells of the brain, microglia can potently modulate neural activity. Stressors during early life have sex-specific effects on microglial development - ultimately increasing risk for psychiatric disorders. Recent studies highlight a role for microglia in both the etiology and pathology of developmental and psychiatric disorders. Specifically, microglia are a key cellular mediator between environmental risk factors for disease and clinical pathology. However, there is a missing gap in understanding the molecular mediators that regulate microglial activity to provide insights for developing therapeutic interventions targeting neuroinflammation. This session will show how environmental insults (immune, microbial, stress) at different developmental stages affect microglia, leading to impaired neural circuit function and altered behavior, often in a sex-biased manner. Our symposium will demonstrate that aberrant developmental phenotypes can be rescued by modifying the microbiome or manipulating microglia either genetically or pharmacologically. The session will span impacts across the lifespan, with Dr. Bordt examining the impact of in utero inflammation and early-life stress on lifelong changes in microglial development and behaviour. Dr. Ciernia will explore the link between the microbiome and microglial development following early postnatal gut inflammation and how this leads to altered sex hormone regulation and behaviour in males. Dr. Bolton will highlight the neuron- and sex-specific effects of early-life adversity on microglial dynamics and synaptic pruning in the developing brain. Together, the three speakers will highlight new findings demonstrating the importance of sex as a mediator of neuro-immune interactions important for regulating behaviour in both health and disease. Member Sponsored Symposia 3 & 4 -- Tuesday, June 25, 10:30 am - 12:00 pm 3. Integrative Strategies and Immunomodulatory Mechanisms of Alternative Treatments to Promote Mental Health in China Various mental disorders, such as depression and neurodegenerative diseases (NDD), are very common worldwide. On the other hand, the efficacy of current mainstream treatments is limited, reflecting unmet and urgent medical needs. For example, first-line clinical antidepressants have low efficacy and a delayed onset of action. This problem is at least partly due to the view that depression is a homogeneous disorder is which treatments are aimed at single target. However, it is now clear that most psychiatric disorders, including depression and NDD-like Parkinson’s disease, are highly heterogeneous disease. This emphasizes the necessity to elucidate the complex mechanisms underlying the heterogeneity of functional domains and networks by using integrative therapeutic strategies. A growing body of evidence indicates that the immune system plays a critical role in both the development and treatment of depression and Parkinson’s disease. As such, modulation of the immune system to improve mental health is now recognized as an important treatment strategy and has led to a new field of study known as immunopsychiatry. However, the critical molecules and pathways that are involved in the underlying mechanisms are still far from understood. A holistic view of disease and alternative interventional strategies have been widely used for investigating the mechanisms and developing treatments for mental disorders in China. For example, Traditional Chinese Medicine derived from herbal and marine animals, meditation and behavioral interventions are increasingly successfully used to treat disease and are of substantial value in the clinic. The systematic role of body-mind interactions, especially gut-brain axis, in mental disorders are being actively investigated. Psychoneuroimmune mechanisms are most certainly involved, although many of them remain to be identified. To address recent developments in traditional Chinese Medicine, this symposium will feature three presentations by leading Chinese scholars on the mainland. They will highlight recent progress from three perspectives: natural marine medicine and Chinese herbal medicine in depression and the gut-brain axis in Parkinson’s disease. Dr. Cai Song is an early pioneer in psychoneuroimmunology and is currently a Chief scientist at BGI Research/Shenzhen Institute of Guangdong Ocean University. She will present the newest discoveries regarding psychoneuroimmunological mechanisms of action by which natural marine medicines are used for the treatment of depression, including anti-inflammatory, anti-oxidative and neuroprotective pathways. Dr. Gang Chen is the Director of the Interdisciplinary Institute for Personalized Medicine on Brain Disorders. He is Founding Chairman of the Chinese Physiological Society’s Committee on Traditional Chinese Medicine and Brain Homeostasis Regulation that recently partnered with PNIRS to host PNIRSAsia-Pacific symposia every year on the mainland. He will highlight the rapid antidepressant effects of the classical multiherbal medicine, Yueju. He will define the advantages of phenotyping for discovering novel neurotransmission and neuroimmune mechanisms underlying depression. Dr. Yan-Qin Shen is the winner of the 2022 Brain, Behavior, and Immunity Impact Award for her discovery of gut-initiated neuroprotection in Parkinson’s disease. Insoluble α-synuclein is a neuronal protein that is strongly implicated in the etiology of Parkinson’s disease. Aggregates of α-synuclein have been found in the gut, suggesting a potential role of dysbiosis in Parkinson’s disease. Professor Shen will present new, unpublished data that establishes a role for the vagus nerve in transmitting α-synuclein aggregates to the brain and defines a novel pathway by which gut permutation leads to accumulation of branch-chain amino acids in the blood and lysosomal dysfunction of microglia. 4. Exploring the Neurotrophic Capacity of Glia in Health and Disease Neurotrophic growth factors have long been known to be important for neuroplasticity and can have a beneficial role in neuropsychiatric and neurodegenerative illness. In addition to neuronal sources, accumulating evidence indicates that neuroglial cells that include microglia and astrocytes can also produce neurotrophins. It also appears that glial cells possess neurotrophic signaling receptors, which may shape their responses to a variety of stimuli. Yet, there has been a paucity of attention devoted to understanding the specific role of glial cells (and their states) in modulating neurotrophic outcomes that could be relevant for a variety of mental illnesses. This symposium speakers will present data showing the novel and important neurotrophic influence that microglia and astrocytes can have in a variety of pathological contexts, including exposure to risk factors for disease. Indeed, it is our contention that these neuroglial cells are fundamental in linking neuroimmune and neuroplastic processes relevant for stress and inflammatory pathology. Dr. Tremblay will present recent data on the outcomes of stress and diet in modulating microglia, including their interactions with neurons and synapses. She will present new findings on “dark” microglia, a state that she discovered and found to become abundant with the exposure to various lifestyle and environmental influences, including stress. The potential of metabolic interventions at rescuing the changes in microglia induced by stress will be further discussed. Dr. Wohleb will present new data showing that neurotrophic signaling in microglia and astrocytes are involved in the synaptogenic and antidepressant-like behavioral effects of clinically-relevant drugs, such as ketamine and psilocybin analogues. Little attention has been devoted to the role of the astrocyte located truncated, TrkB.T1, form of the BDNF receptor in illness. Dr. Hayley will present evidence that deficiency in the truncated, TrkB.T1, BDNF receptor results in a unique sex-dependent anorexic-like phenotype. Disrupted TrkB signalling in glial cells may have consequences for neuronal plasticity that influence a host of appetitive, emotional and other behavioral outcomes. Ultimately, microglia and astrocytes likely exist across a spectrum of phenotypic states that are induced by environmental stressors, immune stimuli, and drug treatment. While some of these engaged states are primarily pro-inflammatory, others appear to have neurotrophic potential. This raises the possibly of harnessing glial phenotypic state for therapeutic potential. The proposed talks will present exciting new data supporting neurotrophic aspects of glial-neuron crosstalk. Member Sponsored Symposia 5 & 6 -- Thursday, June 27, 8:30 - 10:00 am 5. Early Immune Predictors to Identify Offspring At-Risk for Neurodevelopmental Sequelae The Developmental Origins of Health and Disease hypothesis posits that exposure to adverse maternal or early-life environments can significantly impact the health trajectory of offspring. Wide-ranging maternal exposures, from obesity, to stress or substance use, to viral infection, can all result in maternal immune activation. Maternal immune activation, in turn, may impact the placenta and developing fetal brain, increasing risk for child psychopathology including autism spectrum disorder, cognitive dysfunction, attention deficit hyperactivity disorder, and mood and anxiety disorders. This symposium will examine three promising biomarkers to characterize the impact of immune activation on offspring. The first presentation will focus on the placenta, the interface between the maternal and fetal environments, which has been implicated in developmental programming including effects on the developing fetal brain. The second will consider the lactational environment, which has also been demonstrated to shape neonatal and infant brain development. Finally, the third will examine neuroimaging measures of brain development, providing a direct view of inflammatory markers and their consequences on brain development and connectivity. Common themes across the symposium will include the importance of biomarker accessibility, validation, and translatability. 6. Metabolic Dysfunction, Neuroinflammation, and Alzheimer’s Disease Metabolic dysfunction and neuroinflammation are now being targeted in the treatment of Alzheimer’s disease (AD). Impaired brain insulin signaling has recently been established as a key component of AD. While the development of peripheral insulin resistance is well-described, the development of brain insulin dysfunction is poorly understood. There is evidence that the blood-brain barrier (BBB), the brain insulin receptor, and neuroinflammation are involved. While the link between insulin signaling and inflammation is well described in the periphery, a similar relationship in the brain has only begun to be explored. This symposium will bring together international scientists, many new to PNIRS, at varying stages in their careers, from diverse research fields and backgrounds, presenting data gathered from human-derived cells, mice, and humans. Dr. Wenqiang Chen (Joslin Diabetes Research Center, USA) will discuss the role of microglia insulin signaling and the impact on neuroinflammation. Dr. Elizabeth Rhea (University of Washington, USA) will discuss the impact brain and peripheral insulin receptor signaling has on the response to an inflammatory challenge, including the permeability of the BBB. Finally, Dr. Gregory Ruegsegger (University of Wisconsin-River Falls) will present pre-clinical and clinical research on the beneficial effects of exercise on brain insulin signaling and neuroinflammation in the setting of metabolic syndrome. The symposium will be chaired by Dr. William Banks (VA Puget Sound, Seattle, WA), a pioneer in the field of brain-body communication, including neuroendocrinology and neuroimmune interactions, with a focus on the BBB. Taken together, this symposium will highlight a novel link between brain insulin signaling, metabolism, and neuroinflammation. |
