neural cells

Neuro chip records brain cell activity at higher resolution

Brain functions are controlled by millions of brain cells. However, in order to understand how the brain controls functions, such as simple reflexes or learning and memory, we must be able to record the activity of large networks and groups of neurons. Conventional methods have allowed scientists to record the activity of neurons for minutes, but a new technology, developed by University of Calgary researchers, known as a bionic hybrid neuro chip, is able to record activity in animal brain cells for weeks at a much higher resolution. The technological advancement was published in the journal Scientific Reports.

“These chips are 15 times more sensitive than conventional neuro chips,” says Naweed Syed, PhD, scientific director of the University of Calgary, Cumming School of Medicine’s Alberta Children’s Hospital Research Institute, member of the Hotchkiss Brain Institute and senior author on the study. “This allows brain cell signals to be amplified more easily and to see real time recordings of brain cell activity at a resolution that has never been achieved before.”

The development of this technology will allow researchers to investigate and understand in greater depth, in animal models, the origins of neurological diseases and conditions such as epilepsy, as well as other cognitive functions such as learning and memory.

“Recording this activity over a long period of time allows you to see changes that occur over time, in the activity itself,” says Pierre Wijdenes, a PhD student in the Biomedical Engineering Graduate Program and the study’s first author. “This helps to understand why certain neurons form connections with each other and why others won’t.”

The cross-faculty team created the chip to mimic the natural biological contact between brain cells, essentially tricking the brain cells into believing that they are connecting with other brain cells. As a result, the cells immediately connect with the chip, thereby allowing researchers to view and record the two-way communication that would go on between two normal functioning brain cells.

“We simulated what Mother Nature does in nature and provided brain cells with an environment where they feel as if they are at home,” says Syed. “This has allowed us to increase the sensitivity of our readings and help neurons build a long-term relationship with our electronic chip.”

While the chip is currently used to analyze animal brain cells, this increased resolution and the ability to make long-term recordings is bringing the technology one step closer to being effective in the recording of human brain cell activity.

“Human brain cell signals are smaller and therefore require more sensitive electronic tools to be designed to pick up the signals,” says Colin Dalton, adjunct professor in the Department of Electrical and Computer Engineering at the Schulich School of Engineering and a co-author on this study. Dalton is also the facility manager of the University of Calgary’s Advanced Micro/nanosystems Integration Facility (AMIF), where the chips were designed and fabricated.

Researchers hope the technology will one day be used as a tool to bring personalized therapeutic options to patients facing neurological disease.

Supporting the damaged brain

A new study shows that embryonic nerve cells can functionally integrate into local neural networks when transplanted into damaged areas of the visual cortex of adult mice.

(Image caption: Neuronal transplants (blue) connect with host neurons (yellow) in the adult mouse brain in a highly specific manner, rebuilding neural networks lost upon injury. Credit: Sofia Grade, LMU/Helmholtz Zentrum München)

When it comes to recovering from insult, the adult human brain has very little ability to compensate for nerve-cell loss. Biomedical researchers and clinicians are therefore exploring the possibility of using transplanted nerve cells to replace neurons that have been irreparably damaged as a result of trauma or disease. Previous studies have suggested there is potential to remedy at least some of the clinical symptoms resulting from acquired brain disease through the transplantation of fetal nerve cells into damaged neuronal networks. However, it is not clear whether transplanted intact neurons can be sufficiently integrated to result in restored function of the lesioned network. Now researchers based at LMU Munich, the Max Planck Institute for Neurobiology in Martinsried and the Helmholtz Zentrum München have demonstrated that, in mice, transplanted embryonic nerve cells can indeed be incorporated into an existing network in such a way that they correctly carry out the tasks performed by the damaged cells originally found in that position. Such work is of importance in the potential treatment of all acquired brain disease including neurodegenerative illnesses such as Alzheimer‘s or Parkinson’s disease, as well as strokes and trauma, given each disease state leads to the large-scale, irreversible loss of nerve cells and the acquisition of a what is usually a lifelong neurological deficit for the affected person.

In the study published in Nature, researchers of the Ludwig Maximilians University Munich, the Max Planck Institute of Neurobiology, and the Helmholtz Zentrum München have specifically asked whether transplanted embryonic nerve cells can functionally integrate into the visual cortex of adult mice. “This region of the brain is ideal for such experiments,” says Magdalena Götz, joint leader of the study together with Mark Hübener. Hübener is a specialist in the structure and function of the mouse visual cortex in Professor Tobias Bonhoeffer’s Department (Synapses – Circuits – Plasticity) at the MPI for Neurobiology. As Hübener explains, “we know so much about the functions of the nerve cells in this region and the connections between them that we can readily assess whether the implanted nerve cells actually perform the tasks normally carried out by the network.” In their experiments, the team transplanted embryonic nerve cells from the cerebral cortex into lesioned areas of the visual cortex of adult mice. Over the course of the following weeks and months, they monitored the behavior of the implanted, immature neurons by means of two-photon microscopy to ascertain whether they differentiated into so-called pyramidal cells, a cell type normally found in the area of interest. “The very fact that the cells survived and continued to develop was very encouraging,” Hübener remarks. “But things got really exciting when we took a closer look at the electrical activity of the transplanted cells.” In their joint study, PhD student Susanne Falkner and Postdoc Sofia Grade were able to show that the new cells formed the synaptic connections that neurons in their position in the network would normally make, and that they responded to visual stimuli.

The team then went on to characterize, for the first time, the broader pattern of connections made by the transplanted neurons. Astonishingly, they found that pyramidal cells derived from the transplanted immature neurons formed functional connections with the appropriate nerve cells all over the brain. In other words, they received precisely the same inputs as their predecessors in the network. In addition, they were able to process that information and pass it on to the downstream neurons which had also differentiated in the correct manner. “These findings demonstrate that the implanted nerve cells have integrated with high precision into a neuronal network into which, under normal conditions, new nerve cells would never have been incorporated,” explains Götz, whose work at the Helmholtz Zentrum and at LMU focuses on finding ways to replace lost neurons in the central nervous system. The new study reveals that immature neurons are capable of correctly responding to differentiation signals in the adult mammalian brain and can close functional gaps in an existing neural network.

Cancer pt 1

A cancer-y overview

  • the second most common cause of death in developed countries 
  • 29% of all mortality (13% worldwide) 
  • 12.7 million cases, 7.6million deaths in 2008 
  • 14.1 million cases 8.2 million deaths in 2012 

Tumours originate in epithelial cells, cells of the blood and lymph system, connective tissue cells and neural cells

Hallmarks of cancer

Genetic Factors

  • Cancer Producing Genes are known as oncogenes - “Any mutated gene that contributes to neoplastic transformation” 
  • These genes are activated in cancer 
  • Often promote cell growth & survival 
  • “Remove the brakes” from normal tissue homeostasis 
  • Often repress cell death and differentiation
  • Result = lots more cells

Oncogenes

Prior to mutation these are known as “Proto-oncogenes”. Activation can occur by altering gene expression or protein structure (e.g. constitutive activation). Many common oncogenes promote mitosis/progress through cell cycle OR the evasion of death signals.

Activation is caused by genetic changes, including:

  • Point mutations: can result in production of an abnormally functioning protein product.  
  • Deletions: of a few base pairs to loss of an entire chromosome 
  • Gene amplification: resulting in excessive production of oncogene product 
  • Chromosomal translocations: gene is activated inappropriately by another promoter region; caused by rearrangement of parts between nonhomologous chromosomes

Active oncogenes are found in tumours and are thought to be early events in malignant transformation.

Environmental Factors

Carcinogenesis - the process of initiating and promoting cancer

  • Initiationirreversible genetic alteration of a cancer-related gene (oncogene or tumour suppressing gene (TSG)) 
  • Promotion – clonal expansion of the initiated cell (i.e. stimulation of growth) 
  • Progression – stable alteration of an initiated cell. Gaining ability to invade and metastasise 

Carcinogenic agents (will go into detail in future posts)

  • Chemical Carcinogens 
  • Dietary factors 
  • Biological 
  • Viruses
  • Physical 
  • Exposure to ionising radiation

Following exposure to a carcinogenic agent there can be a long latent period before neoplasia develops. This is because the steps of carcinogenesis must be in the right order (initiation, promotion, progression). eg if exposed to a promoter and then an initiator, all is good until exposed to another promoter after the initiator.

The Brain’s Gardeners: Immune Cells ‘Prune’ Connections Between Neurons

A new study, published in the journal Nature Communications, shows that cells normally associated with protecting the brain from infection and injury also play an important role in rewiring the connections between nerve cells. While this discovery sheds new light on the mechanics of neuroplasticity, it could also help explain diseases like autism spectrum disorders, schizophrenia, and dementia, which may arise when this process breaks down and connections between brain cells are not formed or removed correctly.

(Image caption: Microglia (green) with purple representing the P2Y12 receptor which the study shows is a critical regulator in the process of pruning connections between nerve cells)

“We have long considered the reorganization of the brain’s network of connections as solely the domain of neurons,” said Ania Majewska, Ph.D., an associate professor in the Department of Neuroscience at the University of Rochester Medical Center (URMC) and senior author of the study. “These findings show that a precisely choreographed interaction between multiple cells types is necessary to carry out the formation and destruction of connections that allow proper signaling in the brain.”

The study is another example of a dramatic shift in scientists’ understanding of the role that the immune system, specifically cells called microglia, plays in maintaining brain function. Microglia have been long understood to be the sentinels of the central nervous system, patrolling the brain and spinal cord and springing into action to stamp out infections or gobble up dead cell tissue. However, scientists are now beginning to appreciate that, in addition to serving as the brain’s first line of defense, these cells also have a nurturing side, particularly as it relates to the connections between neurons.

The formation and removal of the physical connections between neurons is a critical part of maintaining a healthy brain and the process of creating new pathways and networks among brain cells enables us to absorb, learn, and memorize new information.  

“The brain’s network of connections is like a garden,” said Rebecca Lowery, a graduate student in Majewska’s lab and co-author of the study. “Not only does it require nourishment and a healthy environment, but every once in a while you need to prune dead branches and pull up weeds in order to allow new flowers to grow.”

While this constant reorganization of neural networks – called neuroplasticity – has been well understood for some time, the basic mechanisms by which connections between brain cells are made and broken has eluded scientists.

Performing experiments in mice, the researchers employed a well-established model of measuring neuroplasticity by observing how cells reorganize their connections when visual information received by the brain is reduced from two eyes to one.

The researchers found that in the mice’s brains microglia responded rapidly to changes in neuronal activity as the brain adapted to processing information from only one eye. They observed that the microglia targeted the synaptic cleft – the business end of the connection that transmits signals between neurons. The microglia “pulled up” the appropriate connections, physically disconnecting one neuron from another, while leaving other important connections intact.

This is similar to what occurs during an infection or injury, in which microglia are activated, quickly navigate towards the injured site, and remove dead or diseased tissue while leaving healthy tissue untouched.

The researchers also pinpointed one of the key molecular mechanisms in this process and observed that when a single receptor – called P2Y12 – was turned off the microglia ceased removing the connections between neurons.

These findings may provide new insight into disorders that are the characterized by sensory or cognitive dysfunction, such as autism spectrum disorders, schizophrenia, and dementia. It is possible that when the microglia’s synapse pruning function is interrupted or when the cells mistakenly remove the wrong connections – perhaps due to genetic factors or because the cells are too occupied elsewhere fighting an infection or injury – the result is impaired signaling between brain cells.

“These findings demonstrate that microglia are a dynamic and integral component of the complex machinery that allows neurons to reorganize their connections in the healthy mature brain,” said Grayson Sipe, a graduate student in Majewska’s lab and co-author of the study. “While more work needs to be done to fully understand this process, this study may help us understand how genetics or disruption of the immune system contributes to neurological disorders.”

Novel form of experience-dependent plasticity in the adult brain revealed

Research by a team of scientists from Cologne, Munich and Mainz has shown an unprecedented degree of connectivity reorganization in newly-generated hippocampal neurons in response to experience, suggesting their direct contribution to the processing of complex information in the adult brain.

The hippocampus is an anatomical area of the brain classically involved in memory formation and modulation of emotional behavior. It is also one of the very few regions in the adult brain where resident neural stem cells generate new neurons life-long, thus providing the hippocampal circuitry with an almost unique renewal mechanism important for information processing and mood regulation. In response to experience and voluntary exercise, the amount of new neurons that are incorporated into the hippocampus increases. Dr. Matteo Bergami from CECAD Cologne (Cluster of Excellence in Cellular Stress Responses in Aging-Associated Diseases) has joined efforts with scientists from Ludwig Maximilians University Munich and the University Medical Center of Johannes Gutenberg University Mainz to investigate whether experience, rather than merely promoting neurogenesis, also modifies the connectivity of new neurons.

The scientists successfully showed that the pattern of connectivity of new neurons, namely the number and types of inputs received by each new neuron, is not prefigured in the adult brain but can be significantly altered in response to complex environmental conditions. In fact, following environmental enrichment (EE) the innervation by both local hippocampal interneurons and long distance projection cortical neurons was substantially increased. However, while the inhibitory inputs were largely transient, cortical innervation remained elevated even after ending the exposure to EE. These findings reveal that exposure to complex environmental stimuli as well as their deprivation regulates the way new neurons become incorporated into the preexisting circuitry and thus, their engagement into hippocampal-dependent tasks.

These findings significantly contribute to deepening our understanding of how the brain responds to experience and how external stimuli are translated into stable changes of neuronal connectivity. The results will not only help to decipher how complex learning processes modify the brain’s plasticity, but may also create an experimental basis for investigating the maladaptive changes in brain connectivity associated with neurological and neuropsychiatric disorders such as epilepsy, depression, anxiety, and posttraumatic stress.

The research group’s results represent a crucial step towards realizing the broader vision of CECAD at the University of Cologne, namely to understand the molecular and cellular basis of aging-associated diseases as a means to developing new effective therapeutic strategies.

Turmeric is hands down one of the, if not the, most versatile healing spice in the world with over 600 experimentally confirmed health benefits An exciting new study published in the journal Stem Cell Research & Therapy provides additional support for the concept that curcumin alone is not enough to explain the healing power of turmeric as a whole plant. The study found that a little known, fat-soluble component within turmeric – Ar-tumerone – may make “a promising candidate to support regeneration in neurologic disease.” Titled, “Aromatic-turmerone induces neural stem cell proliferation in vitro and in vivo,” German researchers evaluated the effects of this turmeric-derived compound on neural stem cells (NSCs) – the subgroup of brain cells capable of continuous self-renewal required for brain repair. The study found that when brain cells were exposed to ar-tumerone, neural stem cells increased in number through enhanced proliferation. Moreover, these newly formed neural stem cells also increased the number of fully differentiated neuronal cells, indicating a healing effect was taking place. This effect was also observed in a live animal model, showing that rats injected with ar-tumerone into their brains experienced increases in neural stem cell proliferation and the creation of newly formed healthy brain cells. This study did not go unnoticed by major medical news channels. Here are some good reviews if you wish to explore the implications in greater depth: Newsweek: Curry Power: Turmeric Compound Boosts Growth of Brain’s Stem Cells. .. _ Guardian Liberty Voice: Turmeric Cure Evidence Grows.. _ Monthly Prescribing Reference: Turmeric May Help Regenerate Brain Cells.. _ Times of Malta: Turmeric Link to Brain Cell Repair.. / Medical Daily: Turmeric Helps Your Brain Heal Itself: Spice Up Your Brain- _ Sources: healthimpactnews.com greenmedinfo.com … . _