Yearly Archives: 2018

With the aid of a PET camera, researchers have developed a new method for investigating the dopamine system in the brains of patients suffering from Parkinson’s disease. The method measures levels of a protein called dopamine transporter and could lead to improved diagnosis of Parkinson’s disease. The study was published in Movement Disorders.

Dopamine is a substance produced in the brain and is responsible for controlling our movements. In Parkinson’s disease, dopamine cells degenerate and their loss is responsible for the motor symptoms that characterise the disorder, such as shaking, slowness of movement and difficulty walking.

Using Positron Emission Tomography (PET), a group of researchers have measured the levels of the dopamine transporter protein DAT that regulates the levels of dopamine in the brain. DAT functions as a biomarker for dopamine cells and is present on the surface of the dopamine cells in the cell bodies, on the nerve fibres and on the nerve endings. By measuring where DAT is found, researchers have been able to map the presence of dopamine cells.

The study was based on 20 patients suffering from mild Parkinsonism and an equal number of healthy individuals. The results showed significantly lower amounts of DAT in nerve endings in the Parkinson’s patients than those not suffering from the disease.

Future studies will examine patients with more advanced Parkinson’s, in order to gain a greater understanding of the links between DAT and clinical variables such as motor symptoms and the various stages of the disease.

Paper: “Nigrostriatal dopamine transporter availability in early Parkinson's disease”
Reprinted from materials provided by Karolinska Institutet.

A team of researchers has found that gradually depleting an enzyme called BACE1 reverses the formation of amyloid plaques in the brains of mice with Alzheimer's disease, thereby improving the animals' cognitive function. The study was published in the Journal of Experimental Medicine.

An early event in Alzheimer's is the abnormal buildup of beta-amyloid peptide, which can form large amyloid plaques in the brain and disrupt the function of neuronal synapses. BACE1 helps produce beta-amyloid peptide by cleaving amyloid precursor protein (APP).

Researchers have hypothesized that inhibiting BACE1 could keep the plaques from appearing. However, BACE1 controls many important processes by cleaving proteins other than APP, and mice completely lacking BACE1 have been shown to suffer severe neurodevelopmental defects.  For this study, the researchers  generated mice that gradually lose this enzyme as they grow older. These mice were shown to develop normally and appeared to remain perfectly healthy over time.

The researchers then bred these rodents with Alzheimer's mice. The resulting offspring also formed plaques at this age, even though their BACE1 levels were approximately 50% lower than normal. Remarkably, however, the plaques began to disappear as the mice continued to age and lose BACE1 activity, until, at 10 months old, the mice had no plaques in their brains at all.

Decreasing BACE1 activity also resulted in lower beta-amyloid peptide levels and reversed other hallmarks of Alzheimer's disease, such as the activation of microglial cells and the formation of abnormal neuronal processes.

Loss of BACE1 also improved the learning and memory of mice with Alzheimer's disease. However, when the researchers made electrophysiological recordings of neurons from these animals, they found that depletion of BACE1 only partially restored synaptic function, suggesting that BACE1 may be required for optimal synaptic activity and cognition.

Article: “BACE1 deletion in the adult mouse reverses preformed amyloid deposition and improves cognitive functions”
Reprinted from materials provided by Rockefeller University.

Scientists have developed a novel approach for deep brain stimulation. The new method, published in Science, utilises upconversion nanoparticles to allow delivery of visible light deep into the brain to stimulate neural activities in a less-invasive manner. This innovation marks a significant breakthrough in optogenetics, empowering researchers to uncover valuable insights about the brain.

Optogenetics is a widely adopted research technique in the field of neuroscience that makes use of visible light to activate or inhibit neurons in the brain, enabling researchers to examine the brain’s functions in a minimally invasive manner. The inability of visible light to penetrate into deep brain structures, however, remains a major experimental challenge for this technique, and current deep brain stimulation still requires the insertion of an optical fibre directly into the brain.

To make deep brain stimulation less invasive, the researchers began exploring with near-infrared light, known to possess significantly higher tissue penetration capability and also relatively safe for biological samples. Using a two-step process, upconversion nanoparticles are first introduced into the brain by transcranial injection. Upon reaching deep brain, the implanted upconversion nanoparticles, a unique group of luminescent nanomaterials capable of converting near-infrared light into visible light, then generates visible light which acts to stimulate the neurons. The strategy has shown to be effective in triggering memory recall and dopamine release in the team’s experiments.

This novel approach offers a simpler, less-invasive alternative to fibre-optic implantation for deep brain stimulation, the researchers say, and holds immense potential in facilitating advancement in neuroscience.

Paper: “Near-infrared deep brain stimulation via upconversion nanoparticle–mediated optogenetics”

Reprinted from materials provided by the National University of Singapore.

Higher levels of lifestyle physical activity — such as housecleaning, walking a dog and gardening, as well as exercise — are associated with more gray matter in the brains of older adults, according to a study published in The Journal of Gerontology: Psychological Sciences.

The gray matter in the brain includes regions responsible for controlling muscle movement, experiencing the senses, thinking and feeling, memory and speech and more. The amount of gray matter in the brain often begins to decrease in late adulthood, even before symptoms of cognitive dysfunction appear.

The study measured the levels of physical activity by 262 older adults. Participants wore a noninvasive device called an accelerometer continuously for seven to 10 days. The goal was to accurately measure the frequency, duration and intensity of a participant's activities over that time.

The use of accelerometers was only one of the ways in which this analysis differed from some other investigations of the health of older people. Most research that explores the effects of exercise relies on questionnaires, which ask participants to "self-report" their levels of activity, the researchers said. Moreover, questionnaires tend to ask in a fairly non-specific fashion about types and intensity of exercise.

The study compared gray matter volumes as seen in participants’ MRIs with readings from the accelerometers and other data, which all were obtained during the same year. The analysis found the association between participants' actual physical activity and gray matter volumes remained after further controlling for age, gender, education levels, body mass index and symptoms of depression, all of which are associated with lower levels of gray matter in the brain.

Article: “Accelerometer Physical Activity is Associated with Greater Gray Matter Volumes in Older Adults without Dementia or Mild Cognitive Impairment”
Reprinted from materials provided by Rush University Medical Center.

Scientists have transformed skin cells from patients with Huntington’s disease into the type of brain cell affected by the disorder, creating a new tool to study the degenerative and eventually fatal neurological condition.

The study, published in Nature Neuroscience, showed that the patients’ nerve cells — converted directly from patients’ skin cells — exhibited “symptoms” of the disorder, including DNA damage, dysfunctional mitochondria and cell death. Correcting for malfunctioning genes in these reprogrammed neurons prevented the cell death that is characteristic of Huntington’s disease, an inherited genetic disorder that causes cognitive decline and involuntary muscle movements.

Huntington’s disease and other inherited brain conditions are challenging to study because it is difficult to obtain samples of neurons from living patients. Seeking the next best thing, scientists have found ways to transform skin cells into brain cells.

Their method allows skin cells to bypass the stem cell stage as they are being reprogrammed into neurons. Passing through a stem cell stage resets the developmental clock to an embryonic-like state, wiping out the age-associated effects of the disorder. But the directly reprogrammed neurons retain their age, along with the problems associated with adult-onset Huntington’s disease, according to the researchers.

The researchers say that their technique, which allows them to capture characteristics of the disease at distinct moments in its progression, may also be applied to other conditions as well.

Paper: “Striatal neurons directly converted from Huntington’s disease patient fibroblasts recapitulate age-associated disease phenotypes”
Reprinted from materials provided by Washington University School of Medicine.