Breaking News
October 16, 2018 - Trevena Announces Oliceridine FDA Advisory Committee Meeting Outcome
October 16, 2018 - Study reveals early warning signs of heart problems in patients with newly diagnosed lupus
October 16, 2018 - Connecting the dots of Alzheimer’s disease
October 16, 2018 - New publication offers evidence-based content for global breast imaging medical community
October 16, 2018 - ‘EinsteinVision’ that improves hand-eye coordination of surgeons introduced at Harefield Hospital
October 16, 2018 - WRAIR clinical study evaluates safety and immunogenicity of Marburg vaccine
October 16, 2018 - Ketamine can be considered as alternative to opioids for short-term pain control in ED
October 16, 2018 - Endurance exercise training beneficially alters gut microbiota composition
October 15, 2018 - FDA Approves Yutiq (fluocinolone acetonide intravitreal implant) for Chronic Non-Infectious Posterior Segment Uveitis
October 15, 2018 - Birthing Options for Full-Term Pregnancy
October 15, 2018 - Stressed, toxic, zombie cells seen for first time in Alzheimer’s
October 15, 2018 - Concussion researchers study head motion in high school football hits | News Center
October 15, 2018 - Neuropsychiatric symptoms related to earliest stages of Alzheimer’s brain pathology
October 15, 2018 - Neck collar device may help protect the brain of female high school soccer players
October 15, 2018 - Research reveals how the inner ear processes speech
October 15, 2018 - Many parents still skeptical about safety and effectiveness of flu shot, survey finds
October 15, 2018 - Payer Policies May Discourage Non-Pharma Tx for Low Back Pain
October 15, 2018 - Exercise may delay cognitive decline in people with rare Alzheimer’s disease
October 15, 2018 - Researchers modify CRISPR to reorganize genome | News Center
October 15, 2018 - Innovative brain tumor operation set to tailor to patients’ needs
October 15, 2018 - Findings offer new insight into early changes that occur during AD pathology
October 15, 2018 - Neurons regulating reproductive hormone release have different activity in epileptic mice
October 15, 2018 - More parents are concerned about taking babies swimming in public pools
October 15, 2018 - Health Tip: Know the Risk Factors for Lower Back Pain
October 15, 2018 - Study shows cigarillo flavors enhanced by high-intensity sweeteners
October 15, 2018 - Study traces hospital-acquired bloodstream infections to patients’ own bodies | News Center
October 15, 2018 - Abnormal vision in childhood can affect development of brain areas responsible for attention
October 15, 2018 - Study highlights need for increased support for alcohol-related liver disease patients
October 15, 2018 - Color-changing contact lens could help doctors to monitor eye disease medications
October 15, 2018 - Tobacco heating products cause less staining to teeth than conventional cigarettes
October 15, 2018 - Young adults who are obese can expect to lose up to 10 years in life expectancy
October 15, 2018 - Scientists uncover how proteins meet on the cell membrane
October 15, 2018 - Affordable housing with supportive social services for senior citizens can reduce hospital use
October 15, 2018 - Schiller Easy Pulse Saves Lives
October 15, 2018 - The latest ECG device from Schiller
October 15, 2018 - Following a Tissue Sample
October 15, 2018 - Prisoners need drug and alcohol treatments but AA programs aren’t the answer
October 15, 2018 - Andrea Califano and Jordan Orange Elected to National Academy of Medicine
October 15, 2018 - The impending risk of African Swine Fever Virus
October 15, 2018 - Breastfeeding reduces the number of antibiotic-resistant bacteria in infant gut
October 15, 2018 - Researchers develop comprehensive molecular atlas of postnatal mouse heart development
October 15, 2018 - ObsEva SA Presents Clinical Data from Phase III IMPLANT 2 Trial of Nolasiban in IVF at the American Society of Reproductive Medicine (ASRM) Annual Meeting
October 15, 2018 - Engineering teratoma-derived fibroblasts to enhance osteogenesis
October 15, 2018 - Lab study shows effectiveness of potential therapy for treatment-resistant hypothyroidism
October 15, 2018 - JCU study firms up association between diet and depression
October 15, 2018 - Researchers to study the use of CRISPR on human liver on-a-chip platform
October 15, 2018 - Sub-concussive impacts not associated with decline in neurocognitive function
October 15, 2018 - Researchers find potential treatment to halt premature labor and birth
October 15, 2018 - As U.S. suicides rates rise, Hispanics show relative immunity
October 15, 2018 - FDA Issues a Complete Response Letter to Acacia Pharma for Barhemsys
October 15, 2018 - Photoactive bacteria bait may help in fight against MRSA infections
October 15, 2018 - Increasing vigorous exercise reduces risk factors of type 2 diabetes, cardiovascular disease in children
October 15, 2018 - First-of-its-kind study to test a personalized vaccine in cancer patient
October 15, 2018 - Extension trial assesses benefit of switching from flash monitoring to RT-CGM for hypoglycemia
October 15, 2018 - Half of parents say young children are afraid of doctor’s visits
October 15, 2018 - Study shows how fingerprint-based drug screening works on the living and deceased
October 15, 2018 - Study reveals potential to monitor progression of Alzheimer’s disease by measuring brain antioxidant levels
October 15, 2018 - FDA Approves Xarelto to Reduce the Risk of Major Cardiovascular Events in Patients with Chronic Coronary Artery Disease (CAD) or Peripheral Artery Disease (PAD)
October 15, 2018 - Promising new therapeutic approach against Ebola virus identified
October 15, 2018 - Study unravels how cancer stem cells use normal genes in abnormal ways
October 15, 2018 - Healthcare systems fail to deliver at affordable prices finds report
October 15, 2018 - Intensive BP Therapy in Diabetes May Lower Risk for CV Events
October 15, 2018 - Muscle relaxants increase risk of respiratory complications
October 15, 2018 - Female birds become more promiscuous after hatchings fail in the first breeding attempt
October 15, 2018 - Humans occupied Madagascar thousands of years later than previously thought
October 15, 2018 - Is Kidney Dialysis Always Needed When Septic Shock Strikes?
October 15, 2018 - Study shows invasive lung cancer surgery can lead to long-term opioid use
October 15, 2018 - Sugar, a “sweet” tool to understand brain injuries
October 14, 2018 - King’s commemorates activities and research on World Arthritis Day
October 14, 2018 - Humana and VFW NY team up on Stop 22 initiative to increase awareness of veterans committing suicide
October 14, 2018 - Water fluoridation contributes to urinary fluoride levels in pregnant women in Canada
October 14, 2018 - Study of children in Romanian orphanages tells cautionary tale about family separation
October 14, 2018 - Previous Endologix AFX Safety Notice classified by FDA as Class I recall
October 14, 2018 - Legal scholars sound alarm on academies’ report about returning research results to participants
October 14, 2018 - UNIST selects six extraordinary scholars to be induced as ‘Rising-star Distinguished Professor’
October 14, 2018 - Scientists find new way to help asthmatics breathe more easily
October 14, 2018 - New ‘gag rule’ may adversely impact health care of pregnant women
October 14, 2018 - Rosacea – Genetics Home Reference
October 14, 2018 - When the fighting crosses the line
October 14, 2018 - New findings could benefit patients with triple-negative breast cancer
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