Detection of Asidan
Among autosomal dominant inheritance of spinocerebellar atrophy (SCA) in
Chugoku area in Japan, SCA6 and DRPLA is major (Figure 1). However, we
reported the unique SCA cases accompanied by involvement of motor neuron
systems (, 2).
Collaborative research with Kyoto University (professor Akio Koizumi) has
revealed the causative gene (spinocerebellar ataxia type 36, nicknamed
“Asidan”) in a new disease that has symptoms like those of amyotrophic
lateral sclerosis (ALS) and spinocerebellar degeneration (SCD), which are
known intractable neurological diseases. The study found that this novel
disease is caused by a hexanucleotide repeat in the NOP56 gene on chromosome
20 expanding to approximately 1,500–2,500 repeats. These results were published
in the American Journal of Human Genetics in 2011 (Figure 2, Article 3).
The clinical features of this disease in 8 families were reported in Neurology
in 2012, describing the disease as exhibiting progressive motor neuron
symptoms of the tongue and limbs with relatively pure cerebellar ataxia
(Figure 3,4, Article 4). Further reports to date have also indicated that
cognitive dysfunction, hearing loss (Figure 5), and dysphagia also developed
Furthermore, the progressive loss of NOP56 protein in the spinal cord of
ALS model mice (Article 8) and the giant RNA foci in the neurons of Asidan
patients were reported (Article 9).
Asidan can be a crossroad disease of SCA and ALS in the point of both clinical
and genetic features (Figure 7, 8).
In future, we hope to clarify the pathological mechanism in more detail
by differentiating patient-derived iPS cells into neurons and reproducing
the disease on a cellular level.
||Manabe Y, Shiro Y, Takahashi K, Kashihara K, Abe K (2000) A case of spinocerebellar
ataxia accompanied by severe involvement of the motor neuron system. Neuro
||Ohta Y, Hayashi T, Nagai M, Okamoto M, Nagotani S, Nagano I, Ohmori N,
Takehisa Y, Murakami T, Shoji M, Kamiya T, Abe K (2007) Two cases of spinocerebellar
ataxia accompanied by involvement of the skeletal motor neuron system and
bulbar palsy. Intern Med 46:751-5.
||Kobayashi H, Abe K, Matsuura T, Ikeda Y, Hitomi T, Akechi Y, Habu T, Liu
W, Okuda H, Koizumi A (2011) Expansion of intronic GGCCTG hexanucleotide
repeat in NOP56 causes SCA36, a type of spinocerebellar ataxia accompanied
by motor neuron involvement. Am J Hum Genet 89:121-30.
||Ikeda Y, Ohta Y, Kobayashi H, Okamoto M, Takamatsu K, Ota T, Manabe Y,
Okamoto K, Koizumi A, Abe K (2012) Clinical features of SCA36: a novel
spinocerebellar ataxia with motor neuron involvement (Asidan). Neurology
||Abe K, Ikeda Y, Kurata T, Ohta Y, Manabe Y, Okamoto M, Takamatsu K, Ohta
T, Takao Y, Shiro Y, Shoji M, Kamiya T, Kobayashi H, Koizumi A. (2012)
Cognitive and affective impairments of a novel SCA/MND crossroad mutation
Asidan. Eur J Neurol 19:1070-1078.
||Ikeda Y, Ohta Y, Kurata T, Shiro Y, Takao Y, Abe K. （2012） Acoustic impairment
is a distinguishable clinical feature of Asidan/SCA36. J Neurol Sci 324:109-112.
||Morimoto N, Yamashita T, Sato K, Kurata T, Ikeda Y, Kusuhara T, Murata
N, Abe K. (2012) Assessment of swallowing in motor neuron disease and Asidan/SCA36
patients with new methods. J Neurol Sci 324:149-155.
||Miyazaki K, Yamashita T, Morimoto N, Sato K, Mimoto T, Kurata T, Ikeda
Y, Abe K. (2013) Early and selective reduction of NOP56 (Asidan) and RNA
processing proteins in the motor neuron of ALS model mice. Neurol Res 35:744-754.
||Liu W, Ikeda Y, Hishikawa N, Yamashita T, Deguchi K, Abe K. (2014) Characteristic
RNA foci of the abnormal hexanucleotide GGCCUG repeat expansion in spinocerebellar
ataxia type 36 (Asidan). Eur J Neurol. 21: 1377-1386.
||Ohta Y, Yamashita T, Hishikawa N, Sato K, Matsuzono K, Tsunoda K, Hatanaka
N, Takemoto M, Takemi T, Takamatsu K, Abe K. (2017) Potensional multisystem
degeneratoin in Asidan patients. J Neurol Sci. 373: 2016-2222.
||Matsuzono K, Imamura K, Murakami N, Tsukita K, Yamamoto T, Izumi Y, Kaji
R, Ohta Y, Yamashita T, Abe K, Inoue H. (2017) Antisense Oligonucleotides
Reeduce RNA Foci in Spinocerebellar Ataxia 36 Patient iPSCs. Mol Ther Nucleic
Acids 15:211-219Potensional multisystem degeneratoin in Asidan patients.
J Neurol Sci. 373: 211-212.
Overview of the Department of Neurology, Okayama University
Toru Yamashita, Senior member of staff
The young and attractive Department of Neurology, Okayama University, is
in its 27th year of operation, and 21th year since Prof. Koji Abe assumed the position of director. There are
7 teaching staff members working under Prof. Abe, as well as 11 medical
staff and 3 postgraduates and researchers working enthusiastically on medical
care, education, and research. Including fellow students, young doctors
undergoing training in internal medicine and neurology off campus, as well
as doctors newly appointed as department and section heads at affiliated
hospitals off campus, there is a total of 80 individuals involved in the
laboratory. Our energy has long since been focused on student education
and medical training, and as of 2004, postgraduate clinical training of
doctors became compulsory. To achieve our goal of having ‘all doctors acquire
a wide range of basic clinical skills,’ which is now required, we established
an improved training program with the most appropriate training in the
department of neurology that enables the patient to be thoroughly examined.
The laboratory members work happily together every day to foster highly
skilled neurologists and physicians.
Patients from the Chugoku, Shikoku, Kansai, Kyushu, and the more distantly
located Kanto and Tokai regions are referred to the Department of Neurology
at Okayama University hospital as general new outpatients of Prof. Abe.
New patients are mainly taken care of by Prof. Abe and his staffs. Returning
patients are received through the special outpatient system with amyotrophic
lateral scleosis patients appointed to Dr. Yamashita, neurodegenrative
diseases to Dr. Sato, dementia cases to Dr. Ohta and Dr. Nomura, Parkinson's
disaease cases to Dr. Takemoto and Dr. Tadokoro, neuroimmune diseases to
Dr. Kitayama and Dr. Matsumoto, and stroke to Dr. Tsunoda and Dr. Hishikawa,
who provide advanced medical care to the outpatients. At in-patients ward,
many attending physicians play an active role under Dr. Sato, the Department
of Neurology ward’s medical director. The number of outpatients and inpatients
per year in the Department of Neurology is rapidly increasing, and we have
felt an increasing social demand for the Department of Neurology. The number
of patients referred from affiliated hospitals within and outside of Okayama
prefecture has also increased and cooperation between the departments of
internal medicine, neurology, and brain surgery of regional medical institutions
has grown increasingly closer.
Research activities are being actively expanded in addition to medical
care and educational initiatives. The research system is divided into 3
groups of diseases with the most patients and highest social demand, namely
stroke, neurodegenerative disease, and dementia, for which laboratory members
happily engage in research every day. Many our laboratory members have
the opportunity for studying abroad, including Harvard and Stanford University
in the USA, Toronto University in Canada, and CR CHU in Quebec for international
research activities and there is a great deal of collaborative research
underway. In 2007, for the first time in 14 years, Japan (Osaka) held the
23rd International Symposium on Cerebral Blood Flow and Metabolism (world’s
largest brain science-related conference) with Prof. Abe from our laboratory
as the chairperson. The event was a great success with the most participants
that have ever attended this symposium. Further, in 2009, Prof. Abe was
appointed president of the International Society of Cerebral Blood Flow
and Metabolism, and in Fall 2010, the first World Forum on Cerebral Blood
Flow and Metabolism was hosted in Kyoto. In 2011, the 25th International Symposium on Cerebral Blood Flow and Metabolism was held
in Barcelona, Spain. The 26th Japanese Symposium on Cerebral Blood Flow and Metabolism is scheduled
for November 2014. These events have enabled the Department of Neurology
at Okayama University to contribute to developments in neuroscience, and
thus gain international recognition as a laboratory. In the 21 years that
Prof. Abe has been in his position, 5 new professors in neurology at national
universities have emerged, namely Dr. Mikio Shoji at Hirosaki University
in 2006, and Dr. Tohru Matsuura at Jichi Medical University, Dr. Yoshio
Ikeda at Gunma University, Dr. Etsuro Matsubara at Oita University in 2013,
and Dr. Takeshi Hayashi at Saitama medical university International medical
Center in 2015. Therefore, our laboratory is a place where medical staff
members work together not only for Japan, but for the whole world.
Our Recent Scientific Papers
A prion disease causing peripheral neuropaghy
While human prion diseases have a wide range of clinicopathological phenotypes,
they generally present as neurological disorders with acute multifocal
degeneration of the central nervous system or neuropsychiatric disorders,
most of which are include dementia and cerebellar ataxia.
We discovered a novel prion disease that causes pan-autonomic-sensory neuropathy,
and found that the disease was caused by 2-bp deletion (CT) in the 178th prion protein codon. Prion protein deposits were found in the peripheral
nerves of patients with this disease. These results were published in the
European Journal of Neurology in 2013 (article. 1).
Recently, an English research group reported in the New England Journal of Medicine in 2013 that a prion disease causing very similar clinical symptoms (diarrhea
and autonomic neuropathy) brought about by truncation mutation of the 163rd
prion protein codon (ref. 1), and this similarity has gained much attention.
||Matsuzono K, Ikeda Y, Liu W, Kurata T, Deguchi S, Deguchi K, Abe K (2013)
A novel familial prion disease causing pan-autonomic-sensory neuropathy
and cognitive impairment. Eur J Neurol 20:e67-9.
||Mead S, Gandhi S, Beck J, Caine D, Gallujipali D, Carswell C, Hyare H,
Joiner S, Ayling H, Lashley T, Linehan JM, Al-Doujaily H, Sharps B, Revesz
T, Sandberg MK, Reilly MM, Koltzenburg M, Forbes A, Rudge P, Brandner S,
Warren JD, Wadsworth JD, Wood NW, Holton JL, Collinge J (2013) A novel
prion disease associated with diarrhea and autonomic neuropathy. N Engl
J Med 369:1904-14.
In vivo imaging of cerebral infarction by optical imaging
Cerebral infarction is generally diagnosed using findings from magnetic
resonance imaging and computed tomography; however, the development of
new technology for diagnostic imaging is needed to enable early diagnosis
and to determine treatment outcomes.
Our laboratory created a cerebral infarction model in LC3-GFP transgenic
mice and took images of the mice brains in vivo with the scalp removed
using a special high sensitivity camera. Autophagy was strongly induced
in mice brains in an ischemic state and the emission of light was observed
(figure below). These results were published in Autophagy in 2010 ().
Future developments in luminescent drugs and test equipment may enable
for clinical application simpler and more sensitive detection of cerebral
infarction lesions than current techniques.
||Tian F, Deguchi K, Yamashita T, Ohta Y, Morimoto N, Shang J, Zhang X, Liu
N, Ikeda Y, Matsuura T, Abe K (2010) In vivo imaging of autophagy in a
mouse stroke model. Autophagy 6:1107-14.
Messages from Neurology Researchars and Residents
Fulfilling Life in Graduate School
After graduating agricultural department of Ehime University, I got interested
in a neurodegenerating disease and entered the master's course of department
of neurology of Okayama University graduate school. Furthermore, I would
like to continue the study of neuroscience, and decided to enter the doctoral
It was very glad that I wrote 2 English papers during the master's
course. Also during a doctoral course, from scientific research to my own
daily life, I have received many supports from the doctors and fellow in
our laboratory. It encouraged me to continue research of ALS which is also
a pronoun of a nerve incurable disease.
In our laboratory, there are many doctors, of course Professor
Koji Abe, working in cutting-edge research areas and having many research
performances and experiences. Moreover, since I could have many opportunities
of presentations in scientific conferences and submission papers, I learned
many essential elements required for a researcher. As a result, I already
have submitted 6 original articles in English journals below, and I have
been able to spend a productive graduate student life so far. From now
on, I’m preparing to submit two more papers in English.
I think that the scientific and logical thinking, and the research
technique, which could be obtained during 6 years in my graduate student
life, will be helpful for a life as an advanced researcher in neuroscience
and the job-hunting activities. Thus, I can spend fulfilling days under
very stimulating environment.Moreover, I’m grateful for the generous support
for the job-hunting activities from our laboratory.
Miyazaki K, Masamoto K, Morimoto N, Kurata T, Mimoto T, Obata T, Kanno I, Abe K.
Early and progressive impairment of spinal blood flow-glucose metabolism
coupling in motor neuron degeneration of ALS model mice. J Cereb Blood
Flow. Metab. In press.
Miyazaki K, Ohta Y, Nagai M, Morimoto N, Kurata T, Takehisa Y, Ikeda Y, Matsuura
T, Abe K. Disruption of neurovascular unit prior to motor neuron degeneration
in amyotrophic lateral sclerosis. J Neurosci Res. 2011 May;89(5):718-28.
Miyazaki K, Nagai M, Morimoto N, Kurata T, Takehisa Y, Ikeda Y, Abe K. Spinal anterior
horn has the capacity to self-regenerate in amyotrophic lateral sclerosis
model mice. J Neurosci Res. 2009 Dec;87(16):3639-48.
Miyazaki K, Nagai M, Ohta Y, Morimoto N, Kurata T, Murakami T, Takehisa Y, Ikeda
Y, Kamiya T, Abe K. Changes of Nogo-A and receptor NgR in the lumbar spinal
cord of ALS model mice. Neurol Res. 2009 Apr;31(3):316-21.
Pleasure of Scientific Research
I graduated from department of biotechnological science Kinki University.
I have been interested in brain disease and gone on to a master's course
of department of neurology Okayama University graduate school. I do feel
the passion for research and clinical works of the senior doctors. Although,
I’m not a medical doctor, I want to contribute to patients and work hard
I wrote a paper in English the first year, and three papers
have been published now. I am content to have a lot of opportunities for
presentation at academic societies and seminars. I believe that it is a
very precious experience for you to research connecting the clinical practice,
because you can get not only the knowledge and the technique of the medicine
but also the idea from clinical practice. I hope you get into our company
if you might be interested in our works.
Kawai H, Deguchi S, Deguchi K, Yamashita T, Ohta Y, Omote Y, Kurata T, Ikeda Y,
Matsuura T, Abe K. Protection against ischemic stroke damage by synergistic
treatment with amlodipine plus atorvastatin in Zucker metabolic rat. Brain
Res 2011;1382: 308-314.
Kawai H, Deguchi S, Deguchi K, Yamashita T, Ohta Y, Shang J, Tian F, Zhang X,
Liu N, Liu W, Ikeda Y, Matsuura T, Abe K. Synergistic benefit of combined
amlodipine plus atorvastatin on neuronal damage after stroke in Zucker
metabolic rat. Brain Res, 2011; 1368: 317-323.
Kawai H, Yamashita T, Ohta Y, Deguchi K, Nagotani S, Zhang X, Ikeda Y, Matsuura
T, Abe K. Tridermal tumorigenesis of induced pluripotent stem cells transplanted
in ischemic brain. JCBFM 30; 2010:1487-1493.
Being a Researcher form China
Two elements are indispensable to grow towering tree from a seed. First
element is the gene of the seed and the second is the location where the
seed was planted. Three years ago, I entered PhD course of Neurology in
Okayama University as a foreign student from Luoayang in China. As a result
of having continued my effort to research, I could have published 2 original
papers in the International Journal of autophagy "Autophagy".
Moreover, my study - i.e. " In vivo imaging of autophagy in a mouse
stroke model "- was appeared in the Japanese newspapers and international
version of it. My research life has entered its third year, now I’m writing
other new papers. I think the reason why I could product such results is
the supports from the members of our laboratory. Now I appreciate their
kindness very much. I hope many other Chinese and foreign friends come
to join our attractive projects.
Tian F, Morimoto N, Liu W, Ohta Y, Deguchi K, Miyazaki K, Abe K. In vivo optical
imaging of motor neuron autophagy in a mouse model of amyotrophic lateral
sclerosis. Autophagy. 2011 Sep;7(9):985-92.
Tian F, Deguchi K, Yamashita T, Ohta Y, Morimoto N, Shang J, Zhang X, Liu N,
Ikeda Y, Matsuura T, Abe K. In vivo imaging of autophagy in a mouse stroke
model. Autophagy. 2010 Nov;6(8):1107-14.
Neurology Residence Program
Kosuke Matsuzono M.D.
After graduating the medical school of Kagshima University 3 years ago,
I worked a hospital in Akita prefecture as an intern for two years. Now
I’m in neurology residency training in Okayama University.
We aim for the realization of our motto, “Be gentle to the
patients, be strict with myself, and provide intense and responsible medical
I believe neurology is truly worthwhile career, please come
over to work with us.
Neurology Residence Program
Yoshiko Kouzai M.D.
I graduated the medical school of Ohita University 3 years ago. In order
to be an intern, I came back to my home town Okayama city. Since I was
interested in Neurology, I decided to work as a neurology resident of Okayama
Neurological disorders always inspire me with various clinical
features that patients present. I think that neurology is very interesting
to think about what are our lives.
Scientific Research in PhD Course
Yoshio Omote M.D.
After training as a neurological resident in Okayama University, I entered
the doctoral course of Neurology. Now I’m belonging to the basic and clinical
research about cognition and vascular disease. Amid the heightening talk
about aging society of Japan, patients with stroke, cognitive impairment
and neurodegenerative will increase. If you are interesting in such diseases,
let’s study and work with us.
Clinical Training and Scientific Research
Shoichiro Kohno M.D.
Last year, I began to work neurological resident in Okayama University,
where multidisciplinary and comprehensive strategies are needed to diagnose,
which are making me a strong and smart neurologist. Working in our University
hospital is very appealing in terms of training as a neurologist through
discussions on such cases with the attending doctors.
From this year, I started about the clinical and scientific
study in PhD course of the University with enjoying my work and research
Balancing of Work and Family
Noriko Hatanaka M.D.
After having got pregnant, I have been working as a neurologist in this
department. However, I can make out work while raising two children now
with a support from the doctors’ office. I am enjoying working as a neurologist
here and hope to continue for a long period.