BRAIN RESEARCH INSTITUTENIIGATA UNIVERSITY 2021

Message from the Director

BRI in the time of coronavirus
Osamu Onodera
Director, Brain Research Institute, Niigata University

MEXT Joint Usage / Research Center
The Collaborative Research Center for Brain Diseases
Utilizing Neuropathological Resources
BRI was certified as a joint usage/research center by the Ministry of Education, Culture, Sports, Science and Technology (MEXT) in 2010. Our extensive collection of brain

My name is Osamu Onodera, BRI professor of Neurology. I have
served as the Director since February 2020. The coronavirus
pandemic emerged shortly after my appointment and we havedisease materials and expertise have been open to the neuroscientists' community inJapan. BRI's diverse joint researches in neuropathology and related fields have brought
out a great deal of achievement in relation to unravelling the pathological mechanismof brain disease. Given the MEXT's recognition for such achievements, BRI has renewed

been struggling to deal with various issues arise from the pandemic

the certification of a joint usage/research center in FY 2016.

ever since. I imagine we will have to live with the coronavirus for

BRI has the world-class collections of neuropathological specimens and advanced

the next few years at least. Additionally, there seems to be no goingimaging analysis technique. BRI is committed to tackling tasks such as neuropathological analysis on brain disorders like Alzheimer's disease, development of early diagnostic technique, and translational research on the treatment for reducing disease progression.

back to a previous lifestyle from a new normal. For better or worse, we have come to acknowledge many

By utilizing the specimens of human brain disease and the animal model resources along with the underpinning of translational researchthings in the unprecedented experience. One is the concept of higher education. After experiencing thefor clinical application, BRI's collaboration with researchers across the world offers a prospect of reducing the burden of intractable neu-

pandemic time, there will be a paradigm shift in the perceptions of those receiving higher education. Until
now, universities have provided a physical space for education and screened those who enter the place. But
the online classes, swiftly implemented in response to the pandemic, have virtually eliminated the limitationsof the physical space on their own. This is nothing less than the unprotected exposure of higher education,
which has been secured by the physical element of space, to the world. There is a big change that will allow
students to choose any class in the world. In an age where automatic translation is possible, language barriers

rological disease. Expected outcomes include the followings: to shed light on the disease pathology, to establish early imaging diagnostics, and to discover new treatment that slows disease progression.

Major Research Projects
Revamping the human brain map to elucidate

information(MEXT Joint Usage / Research Center rein-

Clinical research promotion project for neurologicaldisease by establishing the system neuropathology:
Establishing a platform for clinical research utilizing
neuropathological resources (MEXT education and research

forcement project)

activities project)

Finding a cure for age-related diseases of the brain, such as

In therapeutic research of brain disease, the diagnostics bound by

Alzheimer’s and other types of dementia, is an urgent task.

the traditional theory of localization of brain function appears no

In order to develop treatments for such diseases, it is im-

longer sufficient. In order to overcome brain disease, there has been

In recent neuroscience research, large-scale analysis has become the mainstream and the in-situ nature of

portant to establish diagnostic methods that can accurately

an increasing demand for a new academic discipline, which allows

research is being lost. While some suggest building a virtual form of research like network-based laboratories,

estimate the prognosis at an early stage. We need a map

us to understand brain disease in accordance with the functionalin the brain to guide us in predicting the progress of the dis-connectivity of each part of the brain. Niigata University launchedease for that. This map should integrate information on mo-

a project aimed at setting a new pathological assessment method,

exists in me, which genuine discoveries and excitements are nurtured in the context of the physical space. I

lecular diversity at the cellular level, as well as information

naming such neuropathology as “System Pathology for Neurologicalbelieve that the greatest advantage of the institute is that it provides a “place” of chaos, a space for learning.

on functional and anatomical connectivity between cells

Disorders.” Conducting interventional trials based on the knowl-

and regions, and information over time. The project aims toedge will pave a way to overcome brain disease. Connecting thecreate a new map of thecollective expertise in brain at BRI, a number of research projects

human brain that willon neurology at School of Medicine and the medical care system atserve as a guide to un-

University Hospital together, the project aims to ensure a seamless

derstanding the develop-

environment that will readily translate basic scientific findings into

ment of brain diseases.

therapeutic interventions for patients. The project seeks to launch a

are no longer an issue. It’s a huge upheaval for learners. When the education providers lose the superiority ofthe physical space, what can the providers use as a source of strength to maintain its form?
The nature of our learning is called into question in such a time. In this context, I believe that the importanceof learning that shares the space in which we get together will become even more important. In the newnormal, there may be an even greater screening for the education with which we share the space.

a standard form of physically constrained institute may need to change. However, the traditional idea still

In a post-pandemic world, the way the institute is run and the way it is taught could change drastically. We
will be assessed in such a situation. I think the nature of the importance of people gathering closer to haveacademic discussion won’t go away in any era. As a research institute of brain, we will make an effort todevelop such a space in the new academic system of the post-coronavirus era.

and overcome brain diseases: 21 st century
Brodmann areas with integrated multi-level

clinical research center, which will serve for translational research on
brain disease.

HistoryOrganization
Organization
Basic
Neuroscience
BranchBasic
Neuroscience
BranchDept.ofofCellular
CellularNeuropathology
Neuropathology
Dept.

of July
1 2021As As
of July
1 2021

Dept.
Molecular
Neurobiology
Dept.
of of
Molecular
Neurobiology

Visiting
Prof. Hiroyuki
Visiting
Prof.
Hiroyuki
Nawa
Nawa

Dept.
Brain
Tumor
Biology
Dept.
of of
Brain
Tumor
Biology

Assoc.
Prof Nobuyuki
Assoc.
Prof
Nobuyuki
Takei
Takei

Our
goal
is to
understandphysiology
andpathophysiology
Our
goal
is to
understandthethephysiology
andpathophysiology
of ofthethebrain
cellularandmolecularlevels.
established“SLENDR”,
brain
at at
thethecellularandmolecularlevels.
WeWeestablished“SLENDR”,
a techniquebased
in vivogenomeediting,
image
endogenous
a technique
based
on on
in vivogenomeediting,
to to
image
endogenous

Assist.
Prof Yuriko
Assist.
Prof
YurikoIwakuraIwakura

Dept.
Cellular
Neuropathology
Dept.
of of
Cellular
Neuropathology

proteins
withhighspecificity,
resolution
andcontrast
singlecells
proteins
withhighspecificity,
resolution
andcontrast
in insinglecells

Prof. Takayasu
Prof.
Takayasu
Mikuni
Mikunimammalianbrain
tissue(Cell,
2016).
addition,recently
in inmammalianbrain
tissue(Cell,
2016).
In In
addition,
wewerecentlydeveloped“vSLENDR”,
a genome
editing
methodtargetvirtually
developed“vSLENDR”,
a genome
editing
methodto totargetvirtually

Assoc.
Prof. Motokazu
Assoc.
Prof.
Motokazu
Uchigashima
Uchigashimacell-types,
areas
and
ages
acrossbrain,
widelyexpandinganyanycell-types,
areas
and
ages
acrossthethebrain,
widelyexpandingthetheAssist.
Prof. Daisuke
Assist.
Prof.
Daisuke
Satoh
SatohAssist.
Prof. Risa
Assist.
Prof.
Risa
IguchiIguchi

Dept.
SystemPathology
Dept.
of of
SystemPathology
forforNeurological
Disorders
Neurological
DisordersProf. Kazuki
Prof.
KazukiTainakaTainaka

Prof.
Prof.
Takayasu
MikuniTakayasu
Mikuniapplicability
genomeengineering
technologies
broad
field
applicability
of ofgenomeengineering
technologies
in inthethebroad
field
neuroscience(Neuron,2017).
Using“SLENDR”
and“vSLENDR”,
of ofneuroscience(Neuron,2017).
Using“SLENDR”
and“vSLENDR”,
wewe
explorecellularandmolecular
mechanism
underlying
long-lasting
memory,andfurther
investigate
howwillwill
explorethethecellularandmolecular
mechanism
underlying
long-lasting
memory,andfurther
investigate
howthethemechanismis impaired
in memorydisordersprovidenew
therapeuticstrategies.
mechanismis impaired
in memorydisordersto toprovidenew
therapeuticstrategies.

Prof. Masaki
Prof.
Masaki
Ueno
Ueno
Assist.
Prof. Hitoshi
Assist.
Prof.
Hitoshi
UchidaUchidaAssist.
Prof. Satoshi
Assist.
Prof.
SatoshiMiyashita
Miyashita

Pathological
Neuroscience
Pathological
Neuroscience
BranchBranchDept.
Pathology
Dept.
of of
Pathology
Dept.
Molecular
Pathology
Dept.
of of
Molecular
Pathology

Clinical
Neuroscience
BranchClinical
Neuroscience
BranchDept.ofofSystem
SystemPathology
PathologyforforNeurological
NeurologicalDisorders
Disorders
Dept.

Prof. Akiyoshi
Prof.
AkiyoshiKakitaKakitaAssoc.
Prof. Hiroshi
Assoc.
Prof.
Hiroshi
Shimizu
Shimizu

Dept.
Neurosurgery
Dept.
of of
Neurosurgery

Visiting
Prof.
Visiting
Prof.

Current
biopsyandhistology
have
long
reliedthinCurrent
biopsyandhistology
have
long
reliedon onthinsectioned
imageswithseveralchemicalstaining
methods
sectioned
2D2D
imageswithseveralchemicalstaining
methods

KoichiWakabayashi
KoichiWakabayashi

Visiting
Visiting
Fumiaki Mori
Assoc.
Prof. Fumiaki Mori
Assoc.
Prof.

andspecific
immunohistochemistry.
Facilevisualizationandspecific
immunohistochemistry.
Facile
3D3D
visualizationof ofProf. Yukihiko
Prof.
Yukihiko
Fujii
Fujii

novel
concept
neuropathologicaldiagnosis
and
a a
novel
concept
of ofthetheneuropathologicaldiagnosis
and

human
brain
tissuewithsingle-cellresolution
would
providehuman
braintissuewithsingle-cellresolution
would
providecontributeunderstanding
pathologicalmechanisms
contribute
ourourunderstandingof ofpathologicalmechanisms

Assoc.
Prof. Makoto
Assoc.
Prof.
MakotoOishi
Oishi

basedon oncomprehensive
comprehensiveandandquantitative
quantitativeanalysis
analysisof of
based

Assist.
Prof. Tetsuya
Assist.
Prof.
Tetsuya
Hiraishi
Hiraishi
Assist.
Prof. Manabu
Assist.
Prof.
ManabuNatsumeda
Natsumeda

Dept.
Neurology
Dept.
of of
Neurology

Prof. Osamu
Prof.
Osamu
OnoderaOnodera

Prof.
Prof.
KazukiTainaka
KazukiTainaka

individual
biomarker.
In thislaboratory,
at establishing
individual
biomarker.
In thislaboratory,
weweaimaimat establishinga novelneuropathology
developinga highlyefficienta novel
3D3D
neuropathology
by bydevelopinga highlyefficientclearing
protocol
human
brain
tissueandcombiningwithclearing
protocolforforhuman
braintissueandcombiningwitha rapid
imaging
using
light-sheet
fluorescencemicroscopy.
a rapid
3D3D
imaging
using
light-sheet
fluorescencemicroscopy.

Assoc.
Prof. Masato
Assoc.
Prof.
MasatoKanazawa
Kanazawa
Assist.
Prof. Takuya
Assist.
Prof.
TakuyaKonno
Konno

CenterIntegrated
HumanCenterforforIntegrated
Human
Brain
Science
Brain
Science

Dept.
Integrated
Neuroscience
Dept.
of of
Integrated
Neuroscience

Dept.
Biological
Magnetic
Dept.
of of
Biological
Magnetic
Resonance
Resonance

Assoc.
Prof. Hitoshi
Assoc.
Prof.
HitoshiMatsuzawa
Matsuzawa
Assoc.
Prof. Yuji
Assoc.
Prof.
Yuji
SuzukiSuzukiDept.ofofSystem
SystemPathology
PathologyforforNeurological
NeurologicalDisorders
Disorders
Dept.

Assist.
Prof. Yukimi
Assist.
Prof.
YukimiNakamura
Nakamura

Centralnervoussysteminjuriesduestroketraumadisrupt
neuralCentralnervoussysteminjuriesdue
to tostrokeor ortraumadisrupt
neuralProf. Hironaka
Prof.
Hironaka
Igarashi
Igarashicircuits
andresultseveredeficits
functions.
The
brain
and
spinalcord
circuits
andresultin inseveredeficitsof offunctions.
The
brain
and
spinal
cord
have
very
limitedcapacityreconstructcircuitonceis damaged,
and
have
very
limitedcapacity
to toreconstruct
thethecircuitonce
it isit damaged,
andAssoc.
Prof. Kosuke
Assoc.
Prof.
KosukeItohItohtherefore
none
effective
therapeutic
methods
havebeen
developed
therefore
none
of of
effective
therapeutic
methods
havebeen
developed
so so
far.far.

Assist.
Prof. Masaki
Assist.
Prof.
Masaki
Watanabe
Watanabe

Dept.
Functional
Neurology
Dept.
of of
Functional
Neurology&&
Neurosurgery
Neurosurgery
CenterCenterforforBioresourceBioresourcebased
based
Researches
Researches

Bioresource
Dept.
Molecular
Genetics
Bioresource
Dept.
of of
Molecular
Genetics
Science
BranchScience
Branchdynamicallyreorganizedafter
injuriesandinfluencerecoveryprocess
dynamicallyreorganizedafter
injuriesandinfluence
thetherecoveryprocessof ofProf. Hitoshi
Prof.
HitoshiShimadaShimadaProf. Takeshi
Prof.
Takeshi
Ikeuchi
Ikeuchi
Assoc.
Prof. Akinori
Assoc.
Prof.
AkinoriMiyashita
Miyashita
Assist.
Prof. Kensaku
Assist.
Prof.
Kensaku
KasugaKasugaDept.
Comparative
Experimental
Dept.
of of
Comparative&&
Experimental
Medicine
Medicinepreviously
demonstrated
that
sparedmotor
andautonomic
circuits
WeWe
previously
demonstrated
that
sparedmotor
andautonomic
circuits
arearefunctions.
These
resultssuggestthat
controlling
rewiring
circuitfunctions.
These
resultssuggestthat
controlling
thetherewiring
of ofthethecircuit

Prof.
Prof.
Masaki
Ueno
Masaki
Ueno

recovery.
The
goal
study
is to
understandprocess
rewiring
andrecovery.
The
goal
of of
ourourstudy
is tounderstandthetheprocessof ofrewiring
andunderlying
molecular
mechanisms
andneuralfunctions.
Towardaim,
its its
underlying
molecular
mechanisms
andneuralfunctions.
Towardthisthisaim,
analyzingneuralsystemsbothnormalandinjuredbrain
andspinalwewe
areareanalyzingneuralsystemsof of
both
normalandinjuredbrain
andspinalProf. Toshikuni
Prof.
Toshikuni
Sasaoka
Sasaoka

cord,
using
cutting-edge
techniques
including,mousegenetics,
viral
tracers,
cord,
using
cutting-edge
techniques
including,mousegenetics,
viral
tracers,

Lecturer Nanaho
Lecturer
NanahoFukudaFukudaoptogenetics,
chemogenetics,
andbehavior
analysis.
believethat
optogenetics,
chemogenetics,
and3D3D
behavior
analysis.
WeWe
believethatthisthis
study
paves
way
developnovel
strategies
regenerate
circuits
and
study
paves
thetheway
to todevelopnovel
strategies
to toregenerate
circuits
andAssist.
Prof. Kanako
Assist.
Prof.
Kanako
Oda
Oda

Dept.
AnimalModel
Development
Dept.
of of
AnimalModel
Development

would
lead
make
properneuronal
connections
thatachievefunctional
would
lead
to to
make
properneuronal
connections
thatachievefunctional

restoreneuralfunctions.
restoreneuralfunctions.

Prof. Toshikuni
Prof.
Toshikuni
Sasaoka
Sasaoka
Assoc.
Prof. Manabu
Assoc.
Prof.
Manabu
Abe
Abe

Brain
Science Dept.
Dept.
Pathology
Neuroscience
Brain
Scienceof ofPathology
Neuroscience
BranchBranchProf. Akiyoshi
Prof.
AkiyoshiKakitaKakitaDept.ofofPathology
Pathology/ /Dept.
Dept.ofofPathology
PathologyNeuroscience
Neuroscience
Dept.

Assoc.
Prof. Mari
Assoc.
Prof.
Mari
Tada
Tada

Mission:Mission:Assist.
Prof. Rie
Assist.
Prof.
Rie
Saito
Saito

Dept.
Molecular
Neuroscience
Dept.
of of
Molecular
Neuroscience

providehighestqualitypathology
servicesandTo To
providethethehighestqualitypathology
servicesandProf. Osamu
Prof.
Osamu
OnoderaOnoderac iev
uds eodnotnh et haedavadnva
s c isecni et inf itci f iev
d ei dnecn
e cfeo cf o
uc
se
cn
ec
meem
ne
t notf o f

Assoc.
Prof. Taisuke
Assoc.
Prof.
TaisukeKato
Katodevelopmentsin thefieldof neuropathology.
developmentsin thefieldof neuropathology.

Assist.
Prof. Akihiro
Assist.
Prof.
Akihiro
Sugai
Sugai

Dept.
Neuroscience
DiseaseDept.
of of
Neuroscienceof of
Disease

Vision:Vision:Prof. Hideaki
Prof.
HideakiMatsuiMatsuiacademic
pathology
department,deliverAs As
an anacademic
pathology
department,
weweaimaimto todeliver

Assoc.
Prof. Ryuichi
Assoc.
Prof.
RyuichiHishidaHishidaAssoc.
Prof. Tomoyuki
Assoc.
Prof.
Tomoyuki
Yamanaka
Yamanaka
Assoc.
Prof. Atsushi
Assoc.
Prof.
Atsushi
Sugie
Sugie
Assist.
Prof. Eisuke
Assist.
Prof.
Eisuke
Dohi
Dohi

Dept.
Translational
Research
Dept.
of of
Translational
Research

Specially
Specially
Appointed Kouichirou
Appointed
Kouichirou
OkamotoOkamoto
Prof.
Prof.

a highdegreeprofessionalism
clinicopathologicala highdegreeof ofprofessionalism
in inclinicopathological

Prof.
Prof.
AkiyoshiKakitaAkiyoshiKakitadiagnostic
servicesandneuropathology
research,
utilizing
comprehensive
andinnovative
approaches
andbuilding
diagnostic
servicesandneuropathology
research,
utilizing
comprehensive
andinnovative
approaches
andbuilding
departmental
competence
meet
needs
of patients,
institutions,andsociety.
departmental
competence
to to
meet
thetheneedsof patients,
institutions,andsociety.
Our
approachwill
involvetakingadvantageopportunities
advancebothscienceandpractice
Our
approachwill
involvetakingfullfulladvantageof ofopportunities
to toadvanceboththethescienceandpracticeof ofneuropathology
throughindividualandcollaborative
research,whichhopefully
produceleadingpractitioners
andneuropathology
throughindividualandcollaborative
research,whichhopefully
willwill
produceleadingpractitioners
andresearchers.
researchers.

Dept.
Dept. ofof Neurosurgery
Neurosurgery

Dept.
Dept. ofof Molecular
Molecular Genetics
Genetics

Department
Departmentof
ofNeurosurgery,
Neurosurgery,University
UniversityofofNiigata
Niigatawas
wasfounded
foundedby
byProfessor
Professor

RecentRecentresearchresearchandanddevelopment
developmentofofdementia
dementiahas
hasdrasticallydrasticallychanged.
changed.Therapeutic
Therapeuticapproach
approachtotodementia
dementiahas
hasshifted
shiftedfrom
fromsymptomatic
symptomaticdrugs
drugstotodisease-modifying
disease-modifyingdrug.
drug.More
Moreattention
attentionhas
has
been
beenpaid
paidinindementia
dementiato
topathophysiologicalpathophysiologicaldiagnosis
diagnosisbased
basedononbiomarker
biomarkerrather
ratherthanthansymptomsymptombased
baseddiagnosis.
diagnosis.Prospering
Prosperingininresearchresearchby
byvirtuevirtueofofparadigm
paradigmshift,
shift,wewehavehavepioneered
pioneeredresearchresearchthat
thatwill
willbring
bringrevolution
revolutionininclinicalclinicalpracticepracticeofofdementia.
dementia.Our
Ourmission
missionhas
hastwotwoelements;
elements;one
oneisisbiomarker
biomarkerdevelopment,
development,andandthetheotherotherisisgenome
genomeresearchresearchofofdementia.
dementia.We
Weattempt
attemptto
tosee
seethroughthroughpathologicalpathologicalchanges
changesoccurring
occurringininthe
thebrainbrainaffectedaffectedwith
withdementia
dementiausing
usingblood
bloodandandcerebrospinal
cerebrospinalfluid
fluidsamples
samplesfrom
frompreclinicalpreclinicalphase
phasetotosymptomatic
symptomaticphase.
phase.We
Wehavehaveestablishedestablishedlarge
large sample
sample collection
collection ofof genomic
genomic DNA
DNA forfor dementia
dementia disorders.
disorders. Whole
Whole genome/exosome
genome/exosome
analyses
analyseshave
havebeen
beenapplied
appliedininthe
thegenome
genomeanalysis
analysisofofdementia
dementiato
toexplore
explorenovel
novelgenetic
geneticfactors
factorsininJapan.
Japan.We
Wehavehaveprovided
providedaaclinicalclinicalsequence
sequence
examination
examinationfor
forphysicians
physiciansacrossacrossJapan
Japanforforgenetic
geneticdiagnosis
diagnosisofofdementia.
dementia.By
Bythisthiseffort,
effort,wewewillwillcontributecontributeto
tothe
therealization
realizationofofgenome
genomemedicine
medicine
ofofdementia
dementiaininJapan.
Japan.Even
Eventhoughthoughthetheenvironmental
environmentalsurrounding
surroundingofofdementia
dementiaresearchresearchhashasbeenbeendrasticallydrasticallymoving,
moving,wewekeepkeeppioneering
pioneeringthe
thedementia
dementiaresearchresearchwithout
withoutforgetting
forgettingour
ourmission
missionthat
thatwewewillwilldeliverdeliveraabrightbrightfuture
futureto
topatientspatientswith
withdementia.
dementia.

MizuhoMizuhoNakata,
Nakata,“the“thefather
fatherof
ofNeurosurgery
NeurosurgeryininJapan”,
Japan”,inin1953,
1953,becoming
becoming
thethefirst
firstindependent
independentDepartment
Departmentof
ofNeurosurgery
NeurosurgeryininJapan.
Japan.Since
Sincethen,then,thethedepartment
departmenthas
hasledledthethefieldfieldofofpreclinicalpreclinicalresearchresearchandandsurgery
surgeryfor
forbrainbrain
tumors,tumors,cerebral
cerebralvascularvasculardisease,disease,brain
braintrauma,
trauma,and
andfunctional
functionalsurgery.
surgery.
Also,
Also,thethedepartment
departmentisisuniqueuniqueininthat
thatititisisaffiliatedaffiliatedwith
withthetheBrain
BrainResearch
Research
Institute,
Institute,enabling
enablingcollaboration
collaborationwith
withmany
manybasic
basicneuroscience
neurosciencelaboratories
laboratories

Prof.
Prof.
Yukihiko
YukihikoFujii
Fujii

withinwithinthe
theInstitute.
Institute.Answering
Answeringclinicalclinicalquestions
questionsthroughthroughbasic
basicresearchresearchand
andusing
usingthetheresults
resultsto
toimprove
improveclinicalclinicalmedicine,
medicine,isis
precisely
preciselywhat
whatProfessor
ProfessorNakata
Nakataenvisioned
envisionedwhen
whenhehefoundedfoundedthe
theBrain
BrainResearch
ResearchInstitute.
Institute.ItItisisour
ourobligation
obligationto
tocarry
carryononthisthisspirit,
spirit,andandallallstaff
staffisisdedicateddedicatedinindiscovering
discoveringnew
newinsightinsightinto
intoneurosurgicalneurosurgicalpractice.The
practice.Themain
mainresearchresearchareas
areaswe
weare
arecurrently
currentlyfocusing
focusing

Prof.
Prof.
TakeshiTakeshiIkeuchi
Ikeuchiononinclude:
include:(1)establishing(1)establishingbrain
braintumor
tumorcell
celllines
linesandandintracranial
intracranialxenografts
xenograftsto
todevelop
developthe
thebestbeststrategies
strategiesto
totreattreateach
eachtumor,
tumor,(2)(2)
diagnosing
diagnosingbrain
braintumors
tumorsby
bydetecting
detectingdriverdrivermutations
mutationsfrom
fromcellcellfreefreeDNA
DNAof
ofcerebrospinal
cerebrospinalfluid
fluid(Fig(Fig1),
1),(3)(3)identifying
identifyingmolecularmolecularmakersmakersof
ofhumanhumanaxonal
axonalregeneration
regenerationand
anddevelopment,
development,(4)(4)developing
developingassistive
assistivesurgicalsurgicaltechnology
technologyto
toenable
enableaccurate
accuratesimulation
simulation

Dept.
Dept. ofof Comparative
Comparative && Experimental
Experimental Medicine
Medicineforforcomplex
complexneurosurgery
neurosurgerycases
casesandandeducation
educationof
ofyoung
youngneurosurgeons,neurosurgeons,(5)(5)collaboration
collaborationwith
withNishi-Niigata
Nishi-NiigataChuo
ChuoNational
National
Hospital
Hospitalto
toelucidate
elucidatethe
thecomplex
complexpathophysiology
pathophysiologyof
ofepilepsy.
epilepsy.

Dept.
Dept. ofof Neurology
Neurology // Dept.
Dept. ofof Molecular
Molecular Neuroscience
Neuroscience
The
TheNiigata
NiigataUniversity
UniversityBrain
BrainResearch
ResearchInstitute
Institutepossesses
possessesnot
notonly
onlyaabasic
basicneuroscience
neuroscience
branchbranch but
but also
also aa clinicalclinical neuroscience
neuroscience branch:branch: Departments
Departments ofof Neurology
Neurology andand
Neurosurgery.
Neurosurgery.Thus,
Thus,thetheaimaimofofour
ourInstitute
Instituteisistotoovercome
overcomebrain
braindiseases.
diseases.We
Westudy
studyaawide
widevariety
varietyofofbrain
braindiseases
diseasesby
byusingusinggenetic,
genetic,biochemical,
biochemical,cell
cellbiological,
biological,histological,
histological,
andandimaging
imagingapproaches,
approaches,inincollaboration
collaborationwith
withotherotherdepartments
departmentsininthe
theInstitute.
Institute.
InInthethepastpast5050years,
years,wewehavehaveproduced
producedfavorable
favorableresults
resultsofofclinicalclinicalandandbasic
basicresearch.
research.

Prof.
Prof.
Toshikuni
ToshikuniSasaoka
Sasaoka

InInthethebeginning,
beginning,wewerevealed
revealedNiigata
NiigataMinamata
Minamataand
andSMON
SMONdiseases,
diseases,which
whicharearecausedcaused

Prof.
Prof.
Osamu
OsamuOnodera
Onoderabybytoxic
toxicreagents,
reagents,making
makingus
ustotohave
haveprofoundprofoundconnections
connectionswith
withsociety.
society.Up
Uptotonow,
now,weweestablishedestablishedentities
entitiesofofnovel
novelbrain
braindiseases
diseasesandandelucidated
elucidated
their
theiretiologies
etiologiesandanddiseasediseasemechanisms
mechanismsby
bygenetic,
genetic,biochemical,
biochemical,and
andhistologicalhistologicalapproaches.
approaches.
We
Wehavehavealso
alsoeducatededucatedaalarge
largenumber
numberofofneurologists.
neurologists.Careful
Carefulobservation
observationofofpatientspatientsby
bythe
theexcellent
excellentneurologists
neurologistsbrought
broughtus
usfruitfulfruitfulsuccesssuccessininaa
newnewdiscovery.
discovery.Our
Ourresearchresearchisisattributable
attributabletotothe
thesupport
supportofofpatientspatientsand
andclinicians,
clinicians,and
andwe
wewillwillkeep
keeptight
tightconnection
connectionwith
withthem.
them.
Neurologists
Neurologistsneedneedcomprehensive
comprehensiveknowledge
knowledgeofofmedicine
medicineand
andaawide
widerange
rangeofofsocialsocialskills
skillsincluding
includingcommunication,communication,leadership,leadership,and
andproblemproblemsolving
solvingskills.
skills.We
Weactively
activelytrain
trainyoung
youngdoctors
doctorstotoacquireacquirethe
theknowledge
knowledgeandandskills
skillstotobecome
becomeaaspecialist
specialistininvarious
variousfields
fieldsfrom
fromaacutting-edge
cutting-edgebasic
basic
neuroscience
neurosciencetotopracticalpracticalneurology.
neurology.We
Weare
areprofessional
professionalfor
forbrainbraindiseases
diseasesandandwillwillensure
ensurethethebestbestpossible
possiblesupport
supportfor
forourourpatients.
patients.

Dopamine
Dopamineisisthought
thoughtto
toplayplayananimportant
importantrole
roleininmotor
motorcontrol,
control,memory,
memory,learninglearningand
andmotivation.
motivation.We
Wefocus
focus
on
onParkinson's
Parkinson'sdiseasedisease(PD),(PD),which
whichisisone
oneof
ofthe
themostmostcommon
commonneurologicalneurologicaldiseases,
diseases,andandas
asaaPD
PDmodelmodelanimal,animal,we
wedevelop
developaageneticallygeneticallymodified
modifiedmouse
mouseforfordopamine
dopaminereceptors
receptorsand
andtheirtheirrelated
relatedmolecules.
molecules.By
By
analyzing
analyzinganimal
animalbehavior
behaviorand
andneuralneuralcircuit
circuitactivities
activitiesof
ofthe
thePD
PDmodelmodelmice,
mice,we
weaim
aimto
toclarify
clarifythe
theroleroleofofdopamine
dopaminesignaling
signalingon
onmotormotorcontrol,
control,learninglearningand
andmemory,
memory,leading
leadingto
todevelop
developaanew
newtherapeutic
therapeuticapproach
approach
for
forPD.
PD.At
Atthe
thesamesametime,time,we
weare
arestudying
studyingRNA-binding
RNA-bindingproteinsproteinsthat
thatareareresponsible
responsiblefor
fordevelopment
developmentand
andfunctionfunctionofofneuralneuralcircuits
circuitsby
byusingusingmouse
mousegenetics.
genetics.InIncollaboration
collaborationwith
withDept.
Dept.ofofAnimal
AnimalModel
ModelDevelopment,
Development,
we
weare
areconducting
conductingresearchresearchto
toregenerate
regeneratedefective
defectiveorgans
organsby
byembryoembryomanipulation
manipulationusing
usingthetheblastocyst
blastocyst
complementation
complementationmethod.
method.InInaddition,
addition,we
weare
arefocusing
focusingon
ondevelopment
developmentofofan
aninnovative
innovativeembryo
embryomanipulatingmanipulatingsystemsystemfor
forthethegeneration
generationofof
geneticallygeneticallymodified
modifiedmarmosets.
marmosets.
We
Weare
areinincharge
chargeofofadministration
administrationand
andmanagement
managementofofcore
corefacility
facilityfor
foranimal
animalexperiments
experimentsininNiigata
NiigataUniversity
Universitywith
withmice,
mice,rats,
rats,rabbits,
rabbits,
guineaguineapigs,
pigs,dogs,
dogs,pigs,
pigs,JapaneseJapanesemonkeys,
monkeys,marmosets,
marmosets,medaka
medakaetc.
etc.InInaddition
additionto
tosettingsettingup
upthetheexperimental
experimentalenvironment,
environment,wewesupport
supportresearchers
researchersby
byproviding
providingreproductive
reproductiveengineeringengineeringtechnologies
technologiessuch
suchasasininvitro
vitrofertilization,
fertilization,embryo
embryotransfer,transfer,cryopreservation
cryopreservationofofembryos
embryosandandspermatozoa,
spermatozoa,and
andDNA
DNAinjection
injectionto
tooocytes.
oocytes.We
Wealsoalsouseusegenome
genomeediting
editingtechnology
technologyto
tocreate
creategeneticallygeneticallymodified
modifiedanimals
animalsininaashort
short
time
timeperiod.
period.Using
Usingthese
theseexperimental
experimentaltechniques,
techniques,wewemaintain
maintainthe
theanimal
animalfacility
facilityininthe
theSpecific
SpecificPathogen
PathogenFree
Free(SPF)(SPF)environment,
environment,andand
also
alsocontributecontributeto
tothe
theimplementation
implementationofofefficientefficientresearchresearchthroughthroughplannedplannedanimal
animalproduction.
production.

Dept.
Dept. ofof Animal
Animal Model
Model Development
Development
Our
Ourresearchresearchefforts
effortsare
arefocused
focusedon
onunderstanding
understandingof
ofmolecularmolecularmechanisms
mechanismsof
ofhigherhigherbrain
brainfunctions
functionssuch
suchasaslearninglearning
andandmemory.
memory.Making
Makinggood
gooduseuseof
ofcurrent
currentmethods
methodsininmolecularmolecularbiology
biologyand
anddevelopmental
developmentalengineering,
engineering,we
weare
arenownow
engagedengagedininthe
thefollowing
followingprojects:
projects:1)
1)functional
functionalassay
assayofofneurotransmitterneurotransmitterreceptors
receptorsand
andrelated
relatedmolecules
moleculeswith
withgenegenetargetingtargetingtechniques,
techniques,2)2)generation
generationand
andanalysis
analysisof
ofanimalanimalmodels
modelsfor
forhuman
humannervous
nervousdiseases,
diseases,3)3)establishment
establishmentof
ofgermgermline-competentline-competentembryonicembryonicstem
stemcells
cells

Dept.
Dept. ofof Biological
Biological Magnetic
Magnetic ResonanceResonance

derivedderivedfrom
fromratratembryos,
embryos,and
and4)4)development
developmentof
ofbasic
basicmethods
methodsfor
forgeneration
generationof
ofgene-modified
gene-modifiedanimals
animalsusing
usinggene-editing
gene-editingtechnology.
technology.

Continuous
Continuous technological
technological development
development represents
represents anan indispensable
indispensable
component
component ofof thethe recent
recent remarkableremarkable advancements
advancements inin thethe state
state

Dept.
Dept. ofof Neuroscience
Neuroscience ofof Disease
Diseaseofof ourour knowledge
knowledge ofof human
human brain
brain function.
function. Magnetic
Magnetic resonanceresonance

There
Thereexist
existapproximately
approximately100,000,000,000
100,000,000,000neurons
neuronsinineacheachhuman
humanbrain,
brain,and
andthetheisis aa field
field which
which provides
provides aa number
number ofof versatile
versatile non-invasive
non-invasive

numbernumberof
ofgliagliacells
cellsisismuch
muchmore
morethanthanthatthatofofneurons.
neurons.Supposed
Supposedthat
thateacheachneuron
neuronmethodologies
methodologiesapplicableapplicabletotothetheanalysis
analysisof
ofhumanhumanspecificspecificbrain
brain

isisaastar
starininthe
theUniverse,
Universe,wewecould
couldcompare
comparethethebrainbraintotoaasmallsmallUniverse
Universewithin.
within.

function.
function. The
The Department
Department ofof Biological
Biological Magnetic
Magnetic ResonanceResonance focuses
focuses

However,
However,things
thingsarearemoremorecomplicatedcomplicatedbecause
becauseeach
eachneuron
neuronextends
extendslong
longfibers
fiberstotootherotherneurons
neuronsfor
forcommunicating
communicatingsignals.
signals.InInone
onesense,
sense,thethebrain,brain,aasmall
smallUniverse,
Universe,onon thethe research,
research, development
development andand education
education ofof magnetic
magnetic resonanceresonance

Prof.
Prof.
Hironaka
HironakaIgarashi
Igarashi

ItItisistheoretically,
theoretically,technicallytechnicallyand
andphysicallyphysicallyimpossible
impossibleto
tostudy
studyallallthethetwinkling
twinklingstars
starsininthe
thesky.
sky.But
Butwe
wecould
couldestimate
estimatethethecharacterscharactersofoffunctionfunction based
based onon integrated
integrated knowledge
knowledge ofof advanced
advanced engineeringengineeringstars
starsororplanets
planetsby
bycarefully
carefullyobserving
observingand
andanalyzing
analyzingthe
thesunsunandandplanets
planetsininthe
thesolarsolarsystem.
system.ItItisisalso
alsoimpossible
impossibleto
toelucidate
elucidatefunctions,functions,andandnon-linear
non-linearcomputational
computationalanalysis.
analysis.

Dept.
Dept. ofof Functional
Functional Neurology
Neurology && Neurosurgery
Neurosurgery
RecentRecentdevelopment
developmentof
ofininvivo
vivoimaging
imagingenableenableususto
totrack
trackdisruption
disruptionofof brainbrain environment,
environment, such
such asas abnormal
abnormal protein
protein deposition
deposition andandneuroinflammationneuroinflammationininaddition
additionto
toneuronal
neuronalfunction.
function.The
Theaim
aimof
ofour
our
department
departmentare
areto
toinvestigate
investigatethe
thewatershedwatershedbetween
betweenhealthy
healthybrain
brain
aging
agingandandbrainbraindiseases,
diseases,and
andto
toreveal
revealpathologicalpathologicalbases
basesofofdiverse
diversebrain
brain disorders
disorders using
using multimodal
multimodal imaging
imaging technique
technique including
including PET
PET(positron(positron emission
emission tomography)
tomography) andand MRIMRI (magnetic(magnetic resonanceresonance

Prof.
Prof.
Hitoshi
HitoshiShimada
Shimadaisismuchmuchmore
morecomplicatedcomplicatedthan
thanthetheUniverse
Universeitself.
itself.

technologies
technologies asas wellwell asas thethe researchresearch andand education
education ofof human
human brain
brain

imaging).
imaging).We
Wewillwillexecute
executethe
theclinicalclinicalimaging
imagingstudy
studycontributing
contributingto
tofinding
findingout
outpathologicalpathologicalbases
basesofofneuropsychiatricneuropsychiatricdisorders,disorders,leading
leading

Prof.
Prof.
Hideaki
HideakiMatsui
Matsuianatomies
anatomiesandandnetworks
networksof
ofall
allthetheneurons
neuronsone
oneby
byone,
one,but
butwe
weare
areableabletotoreachreachaaright
rightconclusion
conclusionififwe
wehandle
handleaaminiature
miniaturebrain
brainand
anddeducededucecommon
commonprinciples
principlesfrom
fromthethemini-brain.
mini-brain.
This
Thisisisthe
thewaywaythatthatwewehavehavefollowed.
followed.We
Wewillwilldisclose
disclosethethephenomenon
phenomenonoccurring
occurringininhuman
humanbrain
brainbybystudying
studyingFish
Fishbrain.
brain.Especially
Especiallyour
ouraimaimisisto
toelucidate
elucidatethe
themechanism
mechanismof
ofneurologicalneurologicaldiseases
diseasesandanddisorders,disorders,deepening
deepeningscientificscientificand
andsocialsocialunderstanding
understandingfor
forsome,some,oror
finding
findingaadrug
drugforforothers.
others.We
Wehumanhumanbeings
beingshave
haveevolved
evolvedexactly
exactlyfrom
fromFish,Fish,andandmostmostofofthe
thefunctions
functionsand
andstructures
structuresininthe
thehuman
humanbrain
brain
are
arepreserved
preservedininFish
Fishbrain.
brain.Our
Ourlaboratorylaboratoryhas
hastried
trieduncovering
uncoveringthe
thephysiologicalphysiologicalfunctions
functionsand
andpathophysiology
pathophysiologyof
ofthethehuman
humanbrain
brainbybycomparingcomparingFish
Fishandandhuman
humanbrains,brains,and
andwe
wewillwillsurely
surelyfind
findtherapies
therapiesfor
forneurologicalneurologicaldiseases
diseasesandanddisorders.
disorders.

GlobalGlobal Partnerships
Partnerships
GlobalGlobal partnerships
partnerships cancan bring
bring together
together complementarycomplementarystrengths
strengths andand deepen
deepen thethe impact
impact ofof joint
joint research.
research. BRI
BRI isiscommitted
committedto
toforming
formingsuch
suchpartnerships
partnershipsandandwill
willfurther
furtherdedevelop
velopexisting
existingpartnerships.
partnerships.The
Theinstituteinstituteregularly
regularlywelcomes
welcomestoto thethe establishingestablishing novel
novel techniques
techniques ofof early
early diagnosis,
diagnosis, treatment
treatmentscientificscientificvisitors
visitorsfrom
fromaroundaroundthe
theworld
worldandandsigns
signsMOUs
MOUsandandandandprevention,
prevention,bybycollaborating
collaboratingwith
withgovernment,
government,industry,
industry,andandacademic
academicresearchers
researchersinside
insideandandoutside
outsideBrain
BrainResearch
Research

agreements
agreementswith
withoverseas
overseasresearchresearchinstitutions.
institutions.BRI
BRIalsoalsoanan-

Institute.
Institute.As
Asaaleading
leadinglaboratorylaboratoryininthis
thisfield,
field,wewehavehaveambitious
ambitiousplans
planstotocultivate
cultivatehuman
humanresources
resourcescapable
capableof
ofconducting
conducting
translationaltranslationalstudy.
study.

nuallynuallyhosts
hostsinternational
internationalsymposia,
symposia,which
whichfeaturefeaturefascinatingfascinating
lectureslecturesby
bydistinguisheddistinguishedscientists
scientistsfrom
fromacrossacrossthetheworld.
world.

Medical Practice and Education
BRI’s mission is to advance scientific research on the nervous system of the brain. BRI has a historical backgroundthat has developed through the clinical care of neurosurgical cases in the School of Medicine. BRI offering an integrated approach to its research, along with clinical and educational activities, is therefore a great strength. The
research at BRI covers a wide spectrum from Basic Neuroscience to Clinical Neuroscience related research to human brain disease. Pathological Neuroscience that bridges these two areas and the integrated research of thesethree areas brings greater progress, making BRI one of the most desirable institutes for research on brain diseasein Japan. In order to continue to engage in cutting-edge research, BRI is dedicated to training competent researchers. BRI is also dedicated to research in the clinical area to advance medicine.

Niigata Nouken Seminarfor Neuroscience
Niigata Junior Doctor Training School
BRI gave online science talks in October 2020 as part of the master’s
program of “the Niigata Junior Doctor Training School”, a STEM education program aiming at fostering the budding scientists. 37 pupils,
from the 5th grade elementary school to junior high, participated in a
lecture session by two BRI professors.

As part of a two-day event with the International Symposium, BRI
hosts “Niigata Nouken Seminar for Neuroscience”, formerly known
as Summer Seminar, highlighting young and active researchers inneuroscience both at home and abroad. The seminar provides anopportunity to learn the cutting-edge knowledge through lecturesand discussions by specialists. The event in February 2021 marked
its 50th anniversary, which was held online with 144 participants.

Science Education
Partnering with the local Super Science High Schools specified
by MEXT, BRI scientists visit local highschools to give lectures onneuro science. BRI is working to nurture the next generation of
global researchers by introducing the attractive world of neuroscience.

BRAIN RESEARCH INSTITUTENIIGATA UNIVERSITY
1-757 Asahimachidori, Chuo-ku, Niigata 951-8585 Japanwww.bri.niigata-u.ac.jp/en/

Published July 2021