神経化学
APSN/JSNジョイントシンポジウム
アジア人研究者の若手リーダーたちによる脳疾患の病態解明研究 |
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| 7月8日（土） 8:30-10:30 Room G
3SY③-1
アストロサイトに発現するグルタミン合成酵素の制御機構と疾患との関わり
Regulatory mechanism of astroglial glutamate synthetase and its role in CNS health and disease
照沼 美穂
新潟大院 口腔生化学, 新潟市, 日本
Miho Terunuma
Div. of Oral Biochem., Niigata Univ, Niigata, Japan
Metabolism of glutamate, the major excitatory neurotransmitter and precursor of γ-aminobutyric acid (GABA), is mainly dependent on glutamine synthetase (GS) expressed in astrocytes. GS is so far the only enzyme that is capable of converting glutamate to glutamine in the mammalian brain using ammonia as a source of nitrogen. Excess glutamate is an epileptogenic and neurotoxic agent and reduced expression and activity of GS has been found in the patient with mesial temporal lobe epilepsy (Eid et al, Lancet, 2004). Hyperammonemia is also frequently seen in unprovoked convulsive seizure patients (Sato et al, Seizure, 2016). Therefore, fine-tuning glutamate and ammonia metabolism through GS must be important for maintaining brain health. In this symposium, I will introduce the previously unknown molecular mechanism of GS down-regulation in hyperammonemic and hyperglutamate condition which could be the novel target for the development of anti-epileptic drugs. I will also discuss about the regulatory mechanism of GS expression that we have identified recently. | | 7月8日（土） 8:30-10:30 Room G
3SY③-2
Plasticity and Cortical Visual Impairment in Neurodevelopmental Disorders
葉 栢勤
香港中文大学生物医学科学部
Jacque Pak Kan Ip
School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China
Neuronal circuits in mammalian brain are known to be plastic and are subject to experience-driven changes that cause neurons to modify their functional connectivity and responses. Through mechanisms of synaptic plasticity, excitatory synapses are shaped by sensory inputs and learning and experience. Crucially, dysregulated synaptic development and plasticity have been hypothesized to be the underlying cause of altered neuronal function in neurodevelopmental disorders. Yet it remains unclear how impaired synaptic events and aberrant neural circuit formation lead to behavioral deficits in neurodevelopmental disorders. By employing cutting-edge in vivo imaging methods, coupled with proteomic approaches and behavioral paradigms, our work characterizes how different brain regions are affected in neurodevelopmental disorders such as CDKL5 deficiency disorder (CDD). This proposal will address how disruption of CDKL5 protein impacts the functioning of cortical circuits and its relationship with CDD, an autism-related disorder that causes a range of developmental problems including learning disabilities and cognitive impairment. The outcome of this project will shed light on the discovery of novel treatment strategies for CDD and other neurodevelopmental disorders. | | 7月8日（土） 8:30-10:30 Room G
3SY③-3
The dopaminergic system across development: international collaborations to ensure a successful career pathway
Jee Hyun Kim
Institute for Mental and Physical Health and Clinical Translation (IMPACT), School of Medicine, Deakin University, Geelong, Australia
Academic careers in Neurochemistry and Neuropathology are increasingly dependent on collaborations to ensure findings have impact and translational importance. I will describe the importance of international society memberships and tangible benefits arising from such memberships, including the Asian-Pacific Society for Neurochemistry. In addition, I will describe Human Brain Project partner project DOPAMAP (Bjerke et al. 2022 Scientific Data doi.10.1038/s41597-022-01268-8) that was highly successful to produce a public online collection of microscopic images (4607) of immunohistochemically stained dopamine receptor 1 or 2 (D1R or D2R) expressing cells across the forebrain of male and female mice. All images (4607) were registered to the Allen Mouse brain Common Coordinate Framework. These comprehensive in-depth findings show profound sex and age differences in the dopaminergic system and challenges previous findings on D1R and D2R expression in the forebrain. Voltammetry and circuitry studies are now funded to further examine how the age-specific changes in the dopaminergic system contributes to behaviours such as conditioned fear, for which collaborative suggestions are welcomed. | | 7月8日（土） 8:30-10:30 Room G
3SY③-4
Reading m6A RNA Modification Signals in Neurons and at the Synapses
Dan Ohtan Wang, Shengqun Hou, Momoe Sukegawa, Kotaro Mizuta
RIKEN BDR
N6-Methyladenosine (m6A) RNA modification is a highly prevalent RNA modification expressed abundantly in mammalian brain. In recent years, m6A signal has been shown to be required for fundamental brain functions such as development, regeneration, learning and memory, circadian rhythm, and more. But how the signals are transduced into neuronal and synaptic functions remains poorly understood. Previously, we have cataloged synaptically localized m6A-modified transcripts in synaptosomes, which included thousands of modified transcripts involved in neurodevelopmental and neuropsychiatric pathways. Now to understand how in dendrites and axons of neurons is the m6A signal decoded, we focused on two cytoplasmic m6A reader YTH family proteins: YTHDF1 and YTHDF3, and generated transgenic mice models with specific deletion of YTHDF1 or YTHDF3 in mature excitatory neurons. Using a high throughput fluorescence imaging methods, we performed morphometric analysis on thousands of spines in each animal in the cortex, hippocampus, and amygdala. We observed massive alterations. Interestingly the alterations differed in brain regions and in branch types, supporting the functional relevance of m6A signals to local spine development and the circuit connectivity through excitatory synaptic transmission. | |
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