Maldi and Metabolomics

Genetic alterations or early environmental challenges typically lead to many neurobiological changes. While it is certainly possible to predict some of these, the complexity of the brain and the neuronal connectivity make it necessary to use special techniques that go beyond the standard “hypothesis-driven” approach. Over the last decades the research field has developed numerous so-called “hypothesis-free” techniques, such as genome wide association studies, RNA sequencing and proteomics. Together with our collaborators Drs Rob Keijzers and Bill Jordan, we are using two of these techniques: Maldi and metabolomics. Maldi (Matrix Assisted Laser… Read More

Near Infrared Spectroscopy

One of the major technological breakthroughs in human neuroscience research has been the development of functional magnetic resonance imaging (fMRI). This technique, for the first time allowed us to measure changes in blood oxygen levels (and by extension brain activity) while subjects were performing a specific task. Over the years, this technique has been improved and refined especially in spatial, which can now be as small as 1 mm. While structural MRI has also been developed for rats and mice, fMRI is technically very challenging, mainly because of the risk of movement… Read More

Heart Rate Variability

One of the main challenges in behavioural neuroscience is to improve the translational validity of the animal models for the human condition. The lack of success in the development of new drugs for psychiatric disorders has led many pharmaceutical companies to abandon research in the area completely, despite the substantial need for better drugs for mental disorders. To improve the chances of identifying more successful psychoactive drugs, we are evaluating the usefulness of heart rate variability (HRV). HRV refers to the beat-to-beat variation in individual heartbeats. Studies in healthy volunteers have found… Read More

The analysis of ultrasonic vocalizations

Although rats do make audible sounds, most communication, particularly between rats takes places at a frequency beyond our human hearing. These so-called ultrasonic vocalizations (USVs) in rats range from roughly 22 to 90 kHz. Traditionally, USV research has shown that rat calls in the 20 – 25 kHz range are typically associated with negative affect, while calls in the 40 – 90 kHz range are typically associated with positive affect. Rat pups, when separated from their mothers usually make calls in the 30 – 45 kHz range. While this subdivision in three… Read More

The long-term consequences of maternal LPS exposure

LPS, lipopolysaccharide, or better lipopolysaccharides are a group of large molecules consisting of a lipid attached to a polysaccharide. They are found on the outer cell membrane of Gram-negative bacteria and act as an endotoxin. It binds to the CD14/TLR4/MD2 receptor complex that can be found on the membrane of several immune cells (monocytes, dendritic cells, macrophages and B cells). Like PolyI:C, prenatal LPS, while not crossing the blood placental barrier, activates the maternal immune system which ultimately affect the foetus. We currently have two projects aimed at investigating the long-term consequences… Read More

The long-term consequences of maternal polyI:C exposure

Polyinosinic:polycytidylic acid (PolyI:C) is an immunostimulant that simulates viral infections. Like viruses, it does not see to cross the blood placental barrier but activates the maternal immune system by stimulating the TLR3 receptor (which is found on several immune cells, such as B-cells, macrophages and dendritic cells). Components of the maternal immune system, such as interleukin-6 and others are known to cross the blood placental barrier to reach the foetal brain. Interleukins are known to activate microglia (the brain’s immune system) and during development can cause, what is known as a cytokine… Read More

SERT & Drug Addiction

When thinking about addictions, most people tend to think primarily of dopamine. This is not surprising as dopamine plays a very important role in reward and all known drugs of abuse increase dopamine release within the forebrain. However, while dopamine is certainly closely related to the acute reinforcing effect of addictive substances, other neurotransmitters are definitely involved as well. In this project we focus primarily on the role of serotonin. Genetic studies have indicated that alterations in the SERT transporter might make individuals more susceptible to the rewarding properties of drugs of… Read More

Long term biochemical changes in SERT compromised rats

When studying the role of serotonin in mood disorders there is an obvious paradox. We know that one of the most effective treatment for depression and anxiety disorders is blocking the SERT through selective serotonin reuptake inhibitors (SSRIs), leading to an increase in extracellular 5-HT. On the other hand, a genetic reduction in the SERT, which equally leads to increases in extracellular 5-HT, actually increased the risk of depression and anxiety disorder. One possible explanation for this apparent paradox lies in the timing of the increases in extracellular 5-HT. Thus, in the… Read More

The SERT & synaptic plasticity

While 5-HT is best known for its role in mood, cognition and reward, it also plays an important role in the development of the central nervous system. Several studies have found that different serotonin receptors can affect developmental processes such as axon and dendrite maturation, axon guidance and spine formation. This latter is very important, as dendritic spines are essential hubs for neuronal connections, especially excitatory connections that use glutamate as a neurotransmitter. Moreover, dendritic spine changes do not only occur during development, they are also a central element in adult synaptic… Read More

The SERT & Heart Disease

People with psychiatric disorders such as major depression and anxiety disorders are much more likely to also suffer from with heart problems than the general population. Likewise, individuals suffering from heart problems are more likely to develop major depression or anxiety disorders. In other words, there seems to a causal link between depression, anxiety and heart disease. In this project we investigate the hypothesis that high levels of serotonin (5-HT) early in life may be this causal link. The reasoning behind this is that genetic reductions in the SERT are a vulnerability… Read More