Okayama University


Okayama University Medical Research Updates (OU-MRU) Vol.74

January 14, 2020

Source: Okayama University (JAPAN), Public Relations Division
For immediate release: 14 January 2020
Okayama University research: Rising from the ashes—dead brain cells can be regenerated after traumatic injury

(Okayama, 14 January) In a recent study published in Scientific Reports researchers at Okayama University describe the development of a method to generate neurons from other types of cells to compensate for brain cells lost during injury.

A stroke is a debilitating neurological condition that arises when there is deprivation of blood to brain cells. It can lead to loss of memory, motor skills, and cognition. Currently, stroke patients are treated by restoring proper blood flow to their neurons. However, these neurons are often dead by the time treatment is given. Replacing dead neurons is therefore an ideal but very difficult strategy to regain loss of brain function. Now, researchers at Okayama University have now developed a method of converting non-neuronal cells in the brain into neurons for this purpose.

Ascl1, Sox2, and NeuroD1 are proteins found within neurons. When they are introduced tactically into ordinary cells, the cells start showing neuron-like properties. The research team led by Professor ABE Koji and Senior Lecturer YAMASHITA Toru designed their studies based on this principle. Small silicon filaments were first inserted into specific blood vessels within the brains of mice. These filaments clogged the vessels and restricted blood flow thereby giving the mice a stroke.

Three days after a stroke was induced, a delivery system comprising a weakened virus was used to inject Ascl1, Sox2, or NeuroD1 into the damaged brain areas. Viral systems usually attack rapidly-diving, younger cells, and not mature cells like neurons. This gave the team tight control over the type of cells the virus would enter and deposit the proteins into. Indeed, it was observed that protective, non-neuronal cells called as glial cells were the ones targeted successfully.

Twenty-one days after the viral injection these glial cells started presenting markers typically found in young neurons. Forty-nine days after the injection these cells had characteristics of mature neurons, including the branching pattern typical to neurons. The injection of Ascl1, Sox2, or NeuroD1 successfully led to the generation of “new” neurons. The researchers also analysed behavioural patterns of these mice to assess their mobility post stroke. However, in spite of brain cell regeneration their movement was not completely restored.

“Taken together, the present study successfully achieved, for the first time, in vivo direct reprogramming by enforced transcriptional factors (Ascl1, Sox2 and NeuroD1) in the post-stroke mouse brain”, conclude the authors. This successful regeneration of brain cells after a stroke is a step forward in therapy; it remains to be studied whether tweaking this process further can restore neurological function as well.

Stroke: A stroke occurs when oxygen supply to the brain cells is cut off. This is usually the result of an occluded blood vessel or uncontrolled bleeding within the brain. Brain cells can die within minutes of such injury. At present, regeneration of neurons in stroke patients has not been conducted successfully and neuroscientists have been at this endeavour for decades.

Neurons: Neurons are specialized cells that are the building blocks of the brain. Each function controlled by our brain is being executed by specific types of neurons. Thus, the location and function of neurons determines which neurological function will be hampered by a stroke. Given how indispensable neurons are for our day-to-day functioning, preserving healthy neurons and generating younger ones has been an age-old mystery in medical science. Neurons are protected closely by their neighbours: glial cells.

Toru Yamashita, Jingwei Shang, Yumiko Nakano, Ryuta Morihara, Kota Sato, Mami Takemoto, Nozomi Hishikawa, Yasuyuki Ohta, Koji Abe. In vivo direct reprogramming of glial linage to mature neurons after cerebral ischemia. Scientific Reports, (2019) 9:10956.
DOI : https://doi.org/10.1038/s41598-019-47482-0

Correspondence to
Professor ABE Koji, M.D., Ph.D.
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical
Sciences, Okayama University, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan
E-mail: abekabek (a) cc.okayama-u.ac.jp
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Okayama University Medical Research Updates (OU-MRU)
The whole volume : OU-MRU (1- )
Vol.1:Innovative non-invasive ‘liquid biopsy’ method to capture circulating tumor cells from blood samples for genetic testing
Vol.2:Ensuring a cool recovery from cardiac arrest
Vol.3:Organ regeneration research leaps forward
Vol.4:Cardiac mechanosensitive integrator
Vol.5:Cell injections get to the heart of congenital defects
Vol.6:Fourth key molecule identified in bone development
Vol.7:Anticancer virus solution provides an alternative to surgery
Vol.8:Light-responsive dye stimulates sight in genetically blind patients
Vol.9:Diabetes drug helps towards immunity against cancer
Vol.10:Enzyme-inhibitors treat drug-resistant epilepsy
Vol.11:Compound-protein combination shows promise for arthritis treatment
Vol.12:Molecular features of the circadian clock system in fruit flies
Vol.13:Peptide directs artificial tissue growth
Vol.14:Simplified boron compound may treat brain tumours
Vol.15:Metamaterial absorbers for infrared inspection technologies
Vol.16:Epigenetics research traces how crickets restore lost limbs
Vol.17:Cell research shows pathway for suppressing hepatitis B virus
Vol.18:Therapeutic protein targets liver disease
Vol.19:Study links signalling protein to osteoarthritis
Vol.20:Lack of enzyme promotes fatty liver disease in thin patients
Vol.21:Combined gene transduction and light therapy targets gastric cancer
Vol.22:Medical supportive device for hemodialysis catheter puncture
Vol.23:Development of low cost oral inactivated vaccines for dysentery
Vol.24:Sticky molecules to tackle obesity and diabetes
Vol.25:Self-administered aroma foot massage may reduce symptoms of anxiety
Vol.26:Protein for preventing heart failure
Vol.27:Keeping cells in shape to fight sepsis
Vol.28:Viral-based therapy for bone cancer
Vol.29:Photoreactive compound allows protein synthesis control with light
Vol.30:Cancer stem cells’ role in tumor growth revealed
Vol.31:Prevention of RNA virus replication
Vol.32:Enzyme target for slowing bladder cancer invasion
Vol.33:Attacking tumors from the inside
Vol.34:Novel mouse model for studying pancreatic cancer
Vol.35:Potential cause of Lafora disease revealed
Vol.36:Overloading of protein localization triggers cellular defects
Vol.37:Protein dosage compensation mechanism unravelled
Vol.38:Bioengineered tooth restoration in a large mammal
Vol.39:Successful test of retinal prosthesis implanted in rats
Vol.40:Antibodies prolong seizure latency in epileptic mice
Vol.41:Inorganic biomaterials for soft-tissue adhesion
Vol.42:Potential drug for treating chronic pain with few side effects
Vol.43:Potential origin of cancer-associated cells revealed
Vol.44:Protection from plant extracts
Vol.45:Link between biological-clock disturbance and brain dysfunction uncovered
Vol.46:New method for suppressing lung cancer oncogene
Vol.47:Candidate genes for eye misalignment identified
Vol.48:Nanotechnology-based approach to cancer virotherapy
Vol.49:Cell membrane as material for bone formation
Vol.50:Iron removal as a potential cancer therapy
Vol.51:Potential of 3D nanoenvironments for experimental cancer
Vol.52:A protein found on the surface of cells plays an integral role in tumor growth and sustenance
Vol.53:Successful implantation and testing of retinal prosthesis in monkey eyes with retinal degeneration
Vol.54:Measuring ion concentration in solutions for clinical and environmental research
Vol.55:Diabetic kidney disease: new biomarkers improve the prediction of the renal prognosis
Vol.56:New device for assisting accurate hemodialysis catheter placement
Vol.57:Possible link between excess chewing muscle activity and dental disease
Vol.58:Insights into mechanisms governing the resistance to the anti-cancer medication cetuximab
Vol.59:Role of commensal flora in periodontal immune response investigated
Vol.60:Role of commensal microbiota in bone remodeling
Vol.61:Mechanical stress affects normal bone development
Vol.62:3D tissue model offers insights into treating pancreatic cancer
Vol.63:Promising biomarker for vascular disease relapse revealed
Vol.64:Inflammation in the brain enhances the side-effects of hypnotic medication
Vol.65:Game changer: How do bacteria play Tag ?
Vol.66:Is too much protein a bad thing?
Vol.67:Technology to rapidly detect cancer markers for cancer diagnosis
Vol.68:Improving the diagnosis of pancreatic cancer
Vol.69:Early gastric cancer endoscopic diagnosis system using artificial intelligence
Vol.70:Prosthetics for Retinal Stimulation
Vol.71:The nervous system can contribute to breast cancer progression
Vol.72:Synthetic compound provides fast screening for potential drugs
Vol.73:Primary intraocular lymphoma does not always spread to the central nervous system

Okayama University Hospital
(Okayama University Shikata Campus, Okayama City, Japan)