2021 Fiscal Year Research-status Report
Clarification of protective functions of Huntingtin-associated protein 1 against autonomic and motoneuron degeneration using genetically-engineered mice
| Project/Area Number |
20K16108
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| Research Institution | Yamaguchi University |
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Principal Investigator |
イスラム エムディノビウル 山口大学, 大学院医学系研究科, 助教 (80759671)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | Neurodegeneration / HAP1 / Stigmoid body / Enteric nervous system |
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| Outline of Annual Research Achievements |
The expression level of HAP1 in the normal rodent brain/spinal cord varies in different areas with the highest level in the preoptic regions, hypothalamus or amygdala and low level in the cerebral cortex, thalamus, striatum, cerebellum and motoneuons of spinal cord. These brain/spinal cord areas with low HAP1 expression appear to be targets of several of neurodegenerative diseases. These findings lead to the idea that HAP1 is protective against neurodegenerative apoptosis/cell death. In addition to the brain/spinal cord, enteric nervous system (ENS) is an important target of certain neurodegenerative disorders. ENS is also regarded as a potential portal for the pathogenies of neurodegenerative diseases. In this research project, to clarify the in vivo effects of HAP1 on protection of autonomic/motoneurons, I examined the HAP1 expression in ENS. HAP1 immunoreactivity was strongly expressed in both myenteric and submucosal plexuses of ENS. In myenteric plexus, a large number of calretinin, calbindin, NOS, VIP, ChAT, SP, somatostatin, and TH-ir neurons showed HAP1 immunoreactivity. In contrast, most of the CGRP-ir neurons were devoid of HAP1-immunoreactivity. Our current study is the first to clarify that HAP1 is highly expressed in excitatory motor neurons, inhibitory motor neurons, and interneurons but almost absent in sensory neurons in myenteric plexus. These suggest that due to lack of putative STB/HAP1 protectivity, the sensory neurons (Dogiel type II) might be more vulnerable to neurodegeneration than STB/HAP1-expressing Dogiel type I neurons in myenteric plexus.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
We clarified the HAP1 expression in the enteric nervous system and published paper in peer-reviewed journal. Our report was the first in the world to describe the immunohistochemical phenotypes of HAP1 in enteric motor neurons.
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| Strategy for Future Research Activity |
The purpose of this study is to clarify the in vivo protective effects of HAP1 against autonomic and motor neuron degeneration. To achieve the goal, I set out to examine the spatio-temporal expression of HAP1 in the autonomic and motor neurons of spinal cord, in brain stem as well as in enteric neurons. Then I aimed to investigate the changes in developmental pattern and number of autonomic neurons between Wild type and HAP1-KO mice that is produced at our laboratory using CRISPR-Cas9 technology.
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| Causes of Carryover |
Due to COVID-19 pandemic situation all the national and international academic conferences/meetings were cancelled (in person presentation), hence no money was spent for travel purposes. I would like to use this money to pay the publication charge of peer-reviewed journal. In addition, if possible, I would like to use the money to present the research data at international conferences.
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Research Products
(16 results)
