Breaking News
November 12, 2018 - Cocaine Cut With Anti-Worming Drug, Levamisole, May Cause Brain Damage
November 12, 2018 - Obese mice lose a third of their fat using a natural protein
November 12, 2018 - Behind many a Parkinson’s case lurks a mutation in a gene called LRRK2 — why?
November 12, 2018 - Drug with fish oil cuts risk of heart attack, stroke, study finds
November 12, 2018 - Mild exposure to single blast can induce meaningful pathogenic effects, study shows
November 12, 2018 - Miniature pacemakers aim to make heart procedures for infants less invasive, more efficient
November 12, 2018 - Treating pre-cancerous stem cells at early stage could be key to preventing bowel cancer
November 12, 2018 - Kawasaki disease triggered by a combination of factors
November 12, 2018 - Optibrium and University of Nottingham Collaborate on Innovative Teaching Programme
November 12, 2018 - RNA defects linked to multiple myeloma progression in high risk patients
November 12, 2018 - Science is on trial – and we need doctors to provide the defense
November 12, 2018 - Salk researchers receive $19.2 million to unravel mysteries of age-related cognitive decline
November 12, 2018 - KE Eye Centers offer new solution for patients with myopia and astigmatism
November 12, 2018 - Trumpeted new Medicare Advantage benefits will be hard for seniors to find
November 12, 2018 - Biogen and Eisai Announce Presentation of Detailed Analyses from the Phase 1b Long-Term Extension Study of Aducanumab at Clinical Trials on Alzheimer’s Disease (CTAD)
November 12, 2018 - Scientists reveal new cystic fibrosis treatments work best in inflamed airways
November 12, 2018 - Inexpensive and effective drug does not reduce major adverse cardiovascular event rates
November 12, 2018 - Testing coronary calcium levels can better predict patient’s risk for coronary heart disease
November 12, 2018 - FDA conducts mass seizure of food and medical products held under insanitary conditions
November 12, 2018 - FDA Approves Invokana (canagliflozin) to Reduce the Risk of Heart Attack, Stroke or Cardiovascular Death in Adults with Type 2 Diabetes and Established Cardiovascular Disease
November 12, 2018 - Hormone helps reverse brain damage caused by obesity
November 12, 2018 - Grants aim to provide better cancer clinical trial access for military veterans
November 12, 2018 - Mitochondrial DNA may have strong influence on cellular metabolism and disease susceptibility
November 12, 2018 - High stakes, entrenched interests and the Trump rollback of environmental regs
November 12, 2018 - Stem cells transplanted for treatment of Parkinson’s disease
November 12, 2018 - Sandoz Inc. Issues Voluntary Nationwide Recall of One Lot of Losartan Potassium and Hydrochlorothiazide Due to the Detection of Trace Amounts of NDEA (N-Nitrosodiethylamine) Impurity Found in the Active Pharmaceutical Ingredient (API)
November 12, 2018 - Protein found in patients with severe asthma can help identify who would benefit from targeted drugs
November 12, 2018 - Experts develop a list of competencies in antimicrobial prescribing and stewardship
November 12, 2018 - Allied BioScience receives approved label from EPA for new bacteriostatic surface coating
November 12, 2018 - MR Solutions displays elegant bench top CT scanner with clip-on PET and SPECT at EANM congress
November 12, 2018 - FDA announces emergency use authorization of Ebola fingerstick test with portable reader
November 12, 2018 - Grieving spouses with sleep problems have increased risk of chronic immune activation
November 12, 2018 - Exercise routines affect mental health in Japanese expatriates
November 12, 2018 - Fish oil and vitamin D pills no guard against cancer or serious heart trouble
November 12, 2018 - Excess Gestational Weight Gain Not Better for Child Bone Health
November 12, 2018 - Immune receptor provides protective immunity against Group A Streptococcus
November 12, 2018 - Scientists develop new method to produce irradiated nanomaterials for medical applications
November 12, 2018 - Blue light exposure decreases blood pressure
November 12, 2018 - Researchers discover two proteins essential for development of skeletal muscle
November 12, 2018 - Yelp reviews help understand strengths, weaknesses of emergency departments and urgent care centers
November 12, 2018 - Adolescent obesity linked with increased risk of pancreatic cancer later in life
November 12, 2018 - AHA: Poor Teeth-Brushing Habits Tied to Higher Heart Risk
November 12, 2018 - Researchers find how natural killer cells regulate protective HIV antibodies
November 12, 2018 - Rutgers receives $4.2 million federal grant to improve mental health services
November 12, 2018 - Sussex scientists develop a piece of hardware to show how brains function
November 12, 2018 - Study shows pivotal role of parents in efforts to change sexual orientation of LGBT teens
November 12, 2018 - Neck scan detects dementia way before symptoms appear
November 12, 2018 - Risk-profiling can benefit HIV prevention
November 12, 2018 - New thrombolytic based on magnetite nanoparticles successfully tested on animals
November 12, 2018 - Smoking rates go down in the US, lowest since 1965
November 12, 2018 - Phase III Trial of Darolutamide in Patients with Non-metastatic Castration-resistant Prostate Cancer Meets Primary Endpoint
November 12, 2018 - Moderate exercise before conception resulted in lower body weight, increased insulin sensitivity of offspring
November 11, 2018 - Community choirs for older adults reduce loneliness and increase interest in life
November 11, 2018 - Trevena Receives Complete Response Letter for Oliceridine from FDA
November 11, 2018 - More adults and children are using yoga and meditation
November 11, 2018 - Female smokers at greater risk of heart attacks, finds study
November 11, 2018 - Happy Childhood Memories Associated With Better Health
November 11, 2018 - X-linked infantile spinal muscular atrophy – Genetics Home Reference
November 11, 2018 - RNA thought to spread cancer shows ability to suppress breast cancer metastasis
November 11, 2018 - Study finds that thymus plays key role during normal pregnancy
November 11, 2018 - Exploring why some athletes ice their muscles after exercise
November 11, 2018 - Female Genital Mutilation Decreasing in African Nations
November 11, 2018 - Are humans immune to the CRISPR-Cas9 gene editing scissors?
November 11, 2018 - Breastmilk and saliva mixtures regulate oral microbiome of newborn babies
November 11, 2018 - Learning familiar faces through social interactions reduces variability in face recognition
November 11, 2018 - New open source decision support tool could help clinicians chose chemotherapy drugs
November 11, 2018 - New weapons drawn in global TB fight
November 11, 2018 - UCB and Biogen Announce Topline Results from a Phase 2b Study of Dapirolizumab Pegol in Systemic Lupus Erythematosus
November 11, 2018 - Surgery restores boy’s ability to walk post-acute flaccid myelitis
November 11, 2018 - Comorbidity negatively impacts quality of life in people with dementia
November 11, 2018 - Neuroscientists receive $16.75 million from BRAIN Initiative to decipher the brain’s visual system
November 11, 2018 - Purdue researchers invent new smart drainage device to help glaucoma patients
November 11, 2018 - New initiative may benefit entrepreneurs working to transform patient care
November 11, 2018 - Sage Therapeutics Announces FDA Advisory Committee Votes 17-1 in Support of Benefit-Risk Profile of Zulresso (brexanolone) Injection for Treatment of Postpartum Depression
November 11, 2018 - Exercise could delay progression of type 1 diabetes when first diagnosed
November 11, 2018 - Study of gaze fixation in monkeys reveals role of dopamine neurons in response inhibition
November 11, 2018 - Bilingual therapy is vital to improve language disorders in dual-language children, finds study
November 11, 2018 - More Frequent Surveillance No Benefit After NSCLC Resection
November 11, 2018 - Phenylketonuria (PKU) Screening: MedlinePlus Lab Test Information
November 11, 2018 - Researchers discovered a new mechanism of action in a first-line drug for diabetes
Chronic perinatal hypoxia linked to locomotor miscoordination, long-term cerebellar learning deficits

Chronic perinatal hypoxia linked to locomotor miscoordination, long-term cerebellar learning deficits

image_pdfDownload PDFimage_print

Oxygen deprivation associated with preterm birth leaves telltale signs on the brains of newborns in the form of alterations to cerebellar white matter at the cellular and the physiological levels. Now, an experimental model of this chronic hypoxia reveals that those cellular alterations have behavioral consequences.

Chronic sublethal hypoxia is associated with locomotor miscoordination and long-term cerebellar learning deficits in a clinically relevant model of neonatal brain injury, according to a study led by Children’s National Health System researchers published online Aug. 13, 2018, by Nature Communications. Using high-tech optical and physiological methods that allow researchers to turn neurons on and off and an advanced behavioral tool, the research team finds that Purkinje cells fire significantly less often after injury due to perinatal hypoxia. However, an off-the-shelf medicine now used to treat epilepsy enables those specialized brain cells to regain their ability to fire, improving locomotor performance.

Step out of the car onto the pavement, hop up to the level of the curb, stride to the entrance, and climb a flight of stairs. Or, play a round of tennis. The cerebellum coordinates such locomotor performance and muscle memory, guiding people of all ages as they adapt to a changing environment.

“Most of us successfully coordinate our movements to navigate the three-dimensional spaces we encounter daily,” says Vittorio Gallo, Ph.D., Children’s Chief Research Officer and the study’s senior author. “After children start walking, they also have to learn how to navigate the environment and the spaces around them.”

These essential tasks, Gallo says, are coordinated by Purkinje cells, large neurons located in the cerebellum that are elaborately branched like interlocking tree limbs and represent the only source of output for the entire cerebellar cortex. The rate of development of the fetal cerebellum dramatically increases at a time during pregnancy that often coincides with preterm birth, which can delay or disrupt normal brain development.

“It’s almost like a short circuit. Purkinje cells play a very crucial role, and when the frequency of their firing is diminished by injury the whole output of this brain region is impaired,” Gallo says. “For a family of a child who has this type of impaired neural development, if we understand the nature of this disrupted circuitry and can better quantify it, in terms of locomotor performance, then we can develop new therapeutic approaches.”

The research team leveraged a fully automated, computerized apparatus that looks like a ladder placed on a flat surface, encased in glass, with a darkened box at either end. Both the hypoxic and control groups had training sessions during which they learned how to traverse the horizontal ladder, coaxed out of the darkened room by a gentle puff of air and a light cue. Challenge sessions tested their adaptive cerebellar locomotor learning skills. The pads they strode across were pressure-sensitive and analyzed individual stepping patterns to predict how long it should take each to complete the course.

During challenge sessions, obstacles were presented in the course, announced by an audible tone. If learning was normal, then the response to the tone paired with the obstacle would be a quick adjustment of movement, without breaking stride, says Aaron Sathyanesan, co-lead author. Experimental models exposed to perinatal hypoxia showed significant deficits in associating that tone with the obstacle.

“With the control group, we saw fewer missteps during any given trial,” Sathyanesan says. “And, when they got really comfortable, they took longer steps. With the hypoxic group, it took them longer to learn the course. They made a significantly higher number of missteps from day one. By the end of the training period, they could walk along all of the default rungs, but it took them longer to learn how to do so.”

Purkinje cells fire two different kinds of spikes. Simple spikes are a form of constant activity as rhythmic and automatic as a heartbeat. Complex spikes, by contrast, occur less frequently. Sathyanesan and co-authors say that some of the deficits that they observed were due to a reduction in the frequency of simple spiking.

Two weeks after experiencing hypoxia, the hypoxic group’s locomotor performance remained significantly worse than the control group, and delays in learning could still be seen five weeks after hypoxia.

Gamma-aminobutyric acid (GABA), a neurotransmitter, excites immature neurons before and shortly after birth but soon afterward switches to having an inhibitory effect within in the cerebellum, Sathyanesan says. The research team hypothesizes that reduced levels of excitatory GABA during early development leads to long-term motor problems. Using an off-the-shelf drug to increase GABA levels immediately after hypoxia dramatically improved locomotor performance.

“Treating experimental models with tiagabine after hypoxic injury elevates GABA levels, partially restoring Purkinje cells’ ability to fire,” Gallo says. “We now know that restoring GABA levels during this specific window of time has a beneficial effect. However, our approach was not specifically targeted to Purkinje cells. We elevated GABA everywhere in the brain. With more targeted and selective administration to Purkinje cells, we want to gauge whether tiagabine has a more powerful effect on normalizing firing frequency.”

Source:

https://childrensnational.org/

About author

Related Articles