Breaking News
July 20, 2018 - High-performance porous polymeric material for chromatography applications
July 20, 2018 - New molecule shows great promise for future treatment of many cancers
July 20, 2018 - Immune T cells are built to react as fast as possible, shows study
July 20, 2018 - ZHX2 protein could offer a new treatment strategy for kidney cancer
July 20, 2018 - Health burdens of very high risk drinking are potentially large, study reveals
July 20, 2018 - Using miniature drug-filled nanocarriers to target headaches and tumors
July 20, 2018 - Researchers uncover cause for progression of prostate cancer to incurable stage
July 20, 2018 - Studies highlight issues regarding black lung, opioid overdose, police violence and more
July 20, 2018 - AbbVie submits supplemental NDA to FDA for venetoclax to treat acute myeloid leukemia
July 20, 2018 - Researchers are one step closer to developing eye drops to treat age-related macular degeneration (AMD)
July 20, 2018 - Patients maintain muscle mass five years after surgically induced weight loss
July 20, 2018 - AMSBIO introduces new, powerful CRISPR/Cas9 gene editing kits
July 20, 2018 - PureTech Health collaborates with Roche to advance oral administration of antisense oligonucleotides
July 20, 2018 - Analysis reveals disparities in cancer death rates among minority groups
July 20, 2018 - Dr Maddy Parsons receives Royal Microscopical Society Life Science Medal
July 20, 2018 - Study finds link between DNA methylation and non-alcoholic fatty liver disease
July 20, 2018 - Military personnel with head trauma and football players with suspected CTE show similar brain changes
July 20, 2018 - Vidac Pharma Announces Initiation of Phase 2b Clinical Trial of VDA-1102 Ointment in Patients with Actinic Keratosis
July 20, 2018 - KKR is buying Envision Healthcare in a nearly $10B deal
July 20, 2018 - Older people with broken bones face higher risk of death for up to 10 years
July 20, 2018 - A simple pill for meth addicts on the cards
July 20, 2018 - UA researchers to repurpose ketamine to reduce side effects in Parkinson’s patients
July 20, 2018 - Child psychiatrist available on call to help assess separated immigrant children
July 20, 2018 - High bitter-taste sensitivity linked to increased risk of cancer
July 20, 2018 - Falling temperatures may lead to rise in numbers of deaths from stroke
July 20, 2018 - Supplemental oxygen prevents rise in morning blood pressure in OSA patients
July 20, 2018 - High fruit and vegetable intake linked to reduced risk of breast cancer
July 20, 2018 - Careful patient selection may help achieve good outcomes for vaginal mesh surgery
July 20, 2018 - Researchers raise viability of cloned mice using somatic cell nuclear transfer method
July 20, 2018 - 3HP for Latent TB Infection Treatment | 2018 | Newsroom | NCHHSTP
July 20, 2018 - An orange a day keeps macular degeneration away: 15-year study
July 20, 2018 - Researchers elucidate how the brain drives trial-by-trial adaptation to compensate for errors
July 20, 2018 - Understanding triple-negative breast cancer to develop better treatments
July 20, 2018 - Study compares outpatient antibiotic prescribing with traditional medical, retail clinic settings
July 20, 2018 - Immediate Monitoring With ECG Patch Ups A-Fib Diagnosis Rate
July 20, 2018 - KHN’s ‘What the Health?’ Drug prices and unicorns
July 20, 2018 - Scientists seek to better protect the eye from glaucoma
July 20, 2018 - Football training could improve bone mineral density in prostate cancer patients
July 20, 2018 - Single genetic change in gut bacteria can lead to obesity
July 20, 2018 - Research uncovers new target for therapeutic intervention in breast cancer
July 20, 2018 - WFN to highlight clean air for brain health on World Brain Day 2018
July 20, 2018 - Health Highlights: July 17, 2018
July 20, 2018 - Mom’s marijuana winds up in breast milk
July 20, 2018 - Black men could be healthier if seen by black physicians, new research suggests
July 20, 2018 - Alcoholics have persistent difficulties with emotional communication after long-term abstinence
July 19, 2018 - Researchers unravel how ALL invades the central nervous system
July 19, 2018 - Mother’s microbiome determines offspring’s risk of developing autism
July 19, 2018 - Refining standards of maternal-fetal care
July 19, 2018 - Stitching single cells together any which way you want to
July 19, 2018 - Study identifies RNA molecules that regulate male hormones in prostate cancer
July 19, 2018 - New machine-learning model shows promise in predicting undiagnosed dementia
July 19, 2018 - Sleep supports antioxidant processes, study suggests
July 19, 2018 - MiRagen Therapeutics Announces Initiation of Phase 2 Clinical Trial of MRG-201
July 19, 2018 - Unique brain ‘fingerprint’ can predict drug effectiveness
July 19, 2018 - Life on the border: Struggling to survive in Jordan
July 19, 2018 - CT scans may raise brain tumor risk
July 19, 2018 - Moderate alcohol intake linked with improved male fertility
July 19, 2018 - Alcohol-related cirrhosis mortality on the rise among young adults
July 19, 2018 - Study uncovers new protein complex that shields broken DNA ends
July 19, 2018 - Regular sunscreen use protects young people from melanoma
July 19, 2018 - Using non-invasive brain recordings to characterize activity in deep structures
July 19, 2018 - Mediterranean diet could influence academic performance through effects on sleep quality
July 19, 2018 - Woman’s pregnancy history may be linked to Alzheimer’s disease risk
July 19, 2018 - Study calls for new gold standard in research to treat non-alcoholic steatohepatitis
July 19, 2018 - Cancer patients receiving anti-PD-1 therapies may experience delayed skin reactions
July 19, 2018 - Scientists study adverse effects of carbon, silicon nanotubes and carbon nanofibers
July 19, 2018 - Keck Hospital of USC receives Magnet recognition for excellence in nursing
July 19, 2018 - Scientists identify hidden signals in RNAs that control protein synthesis
July 19, 2018 - Quadrivalent HPV Vaccine Not Tied to Spontaneous Abortion
July 19, 2018 - FDA OKs first drug made to reduce excessive sweating
July 19, 2018 - New Finnish study compares surgical treatment of shoulder impingement syndrome to placebo surgery
July 19, 2018 - New findings do no support caffeine as effective appetite suppressant or weight-loss aid
July 19, 2018 - Kite collaborates with Gadeta to develop novel gamma delta TCR therapies for various cancers
July 19, 2018 - Study evaluates Neoteryx’s VAMS technology for monitoring HbA1c levels of diabetic children
July 19, 2018 - New clinical trial examines use of adrenaline to treat cardiac arrests
July 19, 2018 - Early surgical intervention may improve outcomes for patients with mitral valve disease
July 19, 2018 - Prolonged preoperative opioid use linked to adverse outcomes after total knee and hip arthroplasty
July 19, 2018 - Biophysicists use infrared sensor as new method for drug discovery
July 19, 2018 - Rat study shows negative effects of perinatal exposure to phthalates
July 19, 2018 - Children with disabilities endure long waits for life-changing medical equipment
Neuroscientists identify genetic changes in microglia in a mouse model of neurodegeneration and Alzheimer’s disease

Neuroscientists identify genetic changes in microglia in a mouse model of neurodegeneration and Alzheimer’s disease

image_pdfDownload PDFimage_print
Microglia, the brain’s immune cells, scavenge the brain for repairs and to remove potential infectious agents. Credit: Picower Institute for Learning and Memory

Microglia, immune cells that act as the central nervous system’s damage sensors, have recently been implicated in Alzheimer’s disease.

The cells, a type of macrophage that clear away dead cells from the brain and help to maintain healthy neuronal wiring, were found to be entangled with toxic amyloid beta plaques in tissue taken from those suffering from the disease.

Researchers had previously believed that the cells help to protect the brain from neurodegeneration by digesting the amyloid plaques, but it now appears the immune system may play a role in the progression of Alzheimer’s disease.

However, exactly what this role is, and how microglia are transformed from their protective state in healthy brains into a harmful state as the disease progresses, remains unclear.

To better understand microglia and how they respond in this way, a team led by MIT Professor Li-Huei Tsai, director of MIT’s Picower Institute for Learning and Memory, used single-cell RNA sequencing to study individual microglia cells. The research, published in the journal Cell Reports, represents the first time individual microglia have been studied in this way, according to Tsai.

“Right now, microglia are really in the spotlight for a number of neuro-system diseases, including Alzheimer’s, and also schizophrenia,” Tsai says. “However, there are still a lot of very basic things that we don’t know about microglia, such as whether cells in the healthy and diseased brain are all the same, or whether there are different groups, and how they become more inflammatory in the diseased state.”

The researchers used single-cell RNA sequencing to measure active gene expression in individual microglia cells in a mouse model of Alzheimer’s disease previously developed by Tsai’s lab. The mice were engineered so that the gene for a protein called p25 can be overstimulated in the brain, prompting the mice to develop symptoms very similar to those found in Alzheimer’s disease in humans.

The researchers used the technique to study what happens to microglia cells at various points in the progression of neurodegeneration. They measured the cells just before the induction of p25, and then one week, two weeks and six weeks after p25 induction, according to first author Hansruedi Mathys, a postdoc at the Picower Institute.

“This allowed us to follow how microglia respond to the progression of the disease, and the worsening conditions in the mouse brain,” Mathys says.

Surprisingly, they found that just one week after p25 induction, the microglia had already begun to respond to the threat by proliferating more than cells in the control mice.

“This means that the microglia must be able to sense some sort of perturbation in the mouse brain at a very early time point,” Mathys says.

They then looked at the response from the microglia at two and six weeks after p25 induction, and found that the cells had stopped proliferating, and had instead begun to mount a pronounced immune response. Indeed, they found that hundreds of genes relating to an immune response were activated at these later stages of disease progression.

“The microglia initially transition from a resting state into a proliferation state, after which they transition again into a mainly inflammatory state, with very high expression of genes with a very specific immune system function,” Tsai says.

They also discovered distinct groups of microglia, which were found only in the later stages of neurodegeneration. One type of microglia was found to only express interferon response genes, for example, while another only expressed histocompatibility complex class II (MHC) genes.

To find out if these distinct types of microglia overlap geographically, the researchers then performed a technique known as immunostaining to investigate where the populations of cells were distributed in the mouse brain. They stained different sections of the mouse hippocampus with antibodies that recognise particular gene products.

They found that the different types of microglia have very different distribution patterns.

The study is the first to combine single-cell RNA sequencing in microglia with an analysis of gene expression in an inducible model of neurodegeneration, says Tony Wyss-Coray, a professor of neurology and neurological sciences at Stanford University, who was not involved in the research.

“I find it particularly exciting that cells transition through different phases, seemingly following different gene expression programs,” Wyss-Coray says. “This confirms the suspicion that there is a lot of cellular heterogeneity in microglial response to damage, but this paper actually shows this for the first time in a temporal fashion.”

It is also intriguing that microglia show such a strong interferon and MHC class II response, as if reacting to viral infection, he says. “If this response turns out to be key to subsequent neuronal damage, it could provide a novel target for intervention.”

The researchers now hope to investigate whether the genes that are expressed by the microglia, including interferon response genes, might offer a potential new target for drug discovery.

“We’re planning to interfere with type I interferon signalling in this mouse model, to see if it has any beneficial effect on cognition, or disease pathology,” says Mathys.


Explore further:
Overactive scavenger cells may cause neurodegeneration in Alzheimer’s

More information:
Hansruedi Mathys et al. Temporal Tracking of Microglia Activation in Neurodegeneration at Single-Cell Resolution, Cell Reports (2017). DOI: 10.1016/j.celrep.2017.09.039

Journal reference:
Cell Reports

Provided by:
Massachusetts Institute of Technology

Tagged with:

About author

Related Articles