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Treatment of brain diseases at risk if neuroscientists can no longer conduct their research

In order to treat brain diseases such as depression, Alzheimer’s or ADHD, more research into the brain is needed. This cannot be done without animal research. Seventy international brain researchers are warning that animal research is under pressure, thus endangering the further development of treatments.

Over one third of Europeans, some 170 million people, suffer from brain disorders such as ADHD, autism, Parkinson’s disease, Alzheimer’s disease, anxiety disorders and brain tumors. Many of these diseases have a major impact on patients and their families, are not yet curable and have high social costs.

We still know relatively little about the functioning of the brain. As a result, brain diseases are often difficult to treat. Neuroscientists study the entire spectrum of the brain: from molecules and cells to brain regions and from their mutual interactions to ultimately behavior and cognition. They use a variety of research methods to do this, including animal studies. However, this research is increasingly under pressure, which seventy neuroscientists from home and abroad warn about in scientific journal Neuron. They argue that the development of new treatments for brain disorders is at risk.

You can’t know what you don’t know

Because so little is still known about the construction and functioning of the brain, little is known about how brain disorders arise and how they can be treated. Therefore, neuroscientists often don’t know how their research will go and what outcome they can expect. In other words, what they don’t know, they can’t know in advance. In an application for scientific research, however, this is expected. Current regulations allow for research applications to be made for a period of five years. Such an application requires many details about the expected course of the study and the exact design of the experiments. Any deviation from the original application requires new permission. As a result, the quality of research suffers: sometimes there is too little time left to conduct experiments or new scientific insights cannot be incorporated into an experiment. This has consequences for the quality: a researcher is not always able to follow a new line of reasoning based on the results obtained. And that is precisely when the greatest discoveries are made.

Slowdown or standstill

The researchers argue that the system as described above has become too inflexible to make the best choices during experiments. This has consequences for the knowledge they acquire during the research. Experimental animal research is logically accompanied by strict regulations to ensure animal welfare, but the associated increasing administrative burden can cause studies to be delayed or even halted. In the long run, this could lead to no further progress in neuroscience research, which would prevent us as a society from moving closer to possible treatments. The researchers also fear the risk that animal research will move to countries where animal welfare standards differ from the high standards set by the European Union. With their publication, the neuroscientists call for monitoring of the long-term consequences of these increasing administrative restrictions on scientific research.

Alternatives to laboratory animals

Brain research also uses research methods other than just animal testing. In pursuing the 3Rs (replacement, reduction and refinement of laboratory animals), the Netherlands aims to lead the way in animal-free innovations, such as cultured mini-organs. Mini-organs, made from human cells, offer the possibility of answering specific research questions and can be complementary to animal research. But brain diseases are disorders that affect interaction with the environment and alter behavior. A mini-brain will never be able to respond to the environment and cannot exhibit behavior and cognition. Computer systems can also support, but not replace, laboratory animal research. Little is yet known about the brain to build a computer system that can reliably mimic the brain. This makes brain research a field where animal-free research is far from always possible.

Science in brain disorders

Neuroscientists conduct research on how the brain works and why some people get sick and others do not. They also work with doctors to try to understand why some people do not respond to medication, or respond very poorly. This cannot be done without animal studies, because these provide information about the underlying workings of the brain: what happens in the brain when a certain treatment is applied? This is necessary to determine which cells and substances are involved in responses to drugs. This type of research thus contributes significantly to the knowledge of brain diseases, such as ADHD, autism, anxiety disorders, depression, eating disorders, Alzheimer’s, Parkinson’s, epilepsy, ALS and brain tumors: diseases that can hardly be prevented, but which, with new and improved treatment methods, we can do more and more about.

Source: Donders Institute

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Kalsbeek Group

The research of the Kalsbeek research group is focused on those hypothalamic systems that control metabolism, circulation and the immune system. To unravel the mechanisms of hypothalamic integration we study the hypothalamic biological clock and how it enforces its molecular rhythms onto daily physiology and behaviour.

Hypothalamic

The hypothalamus rules those things in life that really matter, such as sex and food, and love and aggression. This ‘primitive’ area at the base of the brain controls all aspects of our lives that are of the utmost importance, but at the same time mostly go unnoticed. Together the various hypothalamic nuclei control how we respond to stress, injury and infection. They determine our appetites for food and water, and subsequently regulate how we use the energy that we have taken in. The hypothalamus ensures a stable blood pressure, blood volume, electrolyte balance and body temperature. Last but not least, the hypothalamus imposes daily rhythms, such as the sleep/wake rhythm, onto our bodies. In other words, the hypothalamus controls the rhythm of our life. These things might seem mundane compared to the intangible mysteries of cognition, but they are of immediate and profound importance for our health and well-being.kalsbeek groep

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Willuhn Group

Neuromodulation & Behavior

This pre-clinical research group headed by Ingo Willuhn is embedded in a larger clinical research team at the AMC department of Psychiatry. The group is driven by the question: “How do we control our behavior?”. Specifically, the Neuromodulation and Behavior group is interested in the neurobiology of compulsive behavior and in mechanisms through which actions become automatic with a focus on basal ganglia function and dopamine signaling. Furthermore, the group studies the effects of deep-brain stimulation (DBS) on brain and behavior.

What is compulsivity? Compulsivity is behavior that is out of control, behavior we perform despite not wanting to perform it or despite its negative outcome. Compulsive behavior is performed persistently, repetitively, and inflexibly. But how does compulsivity develop? What is its neurobiological basis? To answer these questions, we investigate different aspects of compulsivity (e.g., automation of behavior, cognitive (in-)flexibility) and measure/modulate neuronal activity in the brain simultaneously.

Compulsivity is a core feature in several neuropsychiatric disorders, such as obsessive-compulsive disorder (OCD) and drug addiction. In otherwise therapy-resistant patients of such disorders, DBS has been effective. However, our understanding of the mechanisms of action of DBS is still limited. Therefore, we aim to investigate how DBS affects compulsivity and what the neurobiological basis of these effects is.

Our group has a strong collaborative relationship to the Department of Psychiatry at the Amsterdam Medical Center (AMC) lead by Damiaan Denys and therefore has close ties with clinicians and clinical researchers, providing optimal conditions for a translational and multidisciplinary approach. Specifically, we translate clinical findings from studies in humans into relevant animal models, and vice versa we aim to apply our conclusions in the clinical setting. At the very core of our research is the study of rodent behavior. On one hand, we test compulsive behavior itself by using behavioral, (e.g., signal attenuation, schedule-induced polydipsia), pharmacological (drug self-administration), and genetic (SAPAP3-KO mice) animal models. On the other hand, we study “normal’ behavioral faculties such as habit formation, response flexibility, emotion, and cognition (e.g., elevated plus maze, operant chambers) that may contribute to compulsivity when dysregulated. We combine behavioral testing with state-of-the-art research tools including diverse methods for brain stimulation (e.g., DBS, chemogenetics, optogenetics), neurochemical measurements (e.g., microdialysis, fast-scan cyclic voltammetry), calcium imaging (implantable miniaturized microscopes), and electrophysiological recordings (e.g., single-unit activity, local field potentials (LFPs)). Furthermore, we use functional magnetic resonance imaging (fMRI) in rodents to detect the effects of drugs and DBS throughout the brain.

 

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Kamermans Group

My name is Maarten Kamermans. I’m a neuroscientist and head the Retina Signal Processing lab at the Netherlands Institute for Neuroscience. Together with my team we study how vision works.

Vision starts in the retina where images are transformed and coded into neuronal activity relevant for the brain. These coding steps function optimally over a wide range of conditions: from bright day on the beach to a moonless night. Under these very different conditions, specific retinal mechanisms continue to select relevant aspects of the visual world and send this information to the brain.

We are studying the neuronal processing involved in these selection and adaptation processes. This knowledge is essential for understanding how the visual system works and forms the basis for research dedicated to restoring vision in blind people.

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