Pruning the dendritic tree
Study clarifies function of an enzyme for the development of nerve cells


Date:
October 1, 2021
Source:
University of Bonn
Summary:
Researchers have shed light on the function of the enzyme SLK for
the development of nerve cells in the brain. If it is missing, the
neurons' branches are less abundant. In addition, it is then more
difficult to inhibit the activity of the cells. This is consistent
with the fact that there is less SLK in diseased brain tissue from
epilepsy patients.

Epileptic seizures are characterized by overexcitation of neuron
clusters. The findings may help to improve treatment of the
disease. The study is published in the prestigious Journal of
Neuroscience.



FULL STORY ========================================================================== Researchers at the University of Bonn have shed light on the function of
the enzyme SLK for the development of nerve cells in the brain. If it is missing, the neurons' branches are less abundant. In addition, it is then
more difficult to inhibit the activity of the cells. This is consistent
with the fact that there is less SLK in diseased brain tissue from
epilepsy patients. Epileptic seizures are characterized by overexcitation
of neuron clusters. The findings may help to improve treatment of the
disease. The study is published in the Journal of Neuroscience.


==========================================================================
SLK belongs to the large group of kinases. These enzymes are extremely important: They attach phosphate groups (which are small molecular
residues with a phosphorus atom in the center) to proteins and thus
alter their activity. Kinases are involved in the regulation of almost
all life processes in animals.

The kinase SLK was already known to play an important role in embryonic development: One of its effects is on the growth of cells and their
migration in the body; these processes are also essential for the
maturation of neurons.

"We therefore investigated what function SLK performs in nerve cells,"
explains Prof. Dr. Albert Becker from the Institute of Neuropathology
at the University of Bonn.

The researchers inhibited the production of the SLK protein in neurons
of mice.

"This changed the appearance of the neurons," says Anne Quatraccioni,
who is doing her doctorate at the Institute of Neuropathology in the
research group of Prof. Dr. Susanne Schoch McGovern: "The dendrites, which
are the extensions that receive signals from other neurons and conduct
them to the cell body, branched less." SLK deficiency makes neurons
more excitable The dendrites resemble a kind of tree dotted with tiny
contact points, the synapses. This is where extensions of other nerve
cells dock and transmit electrical impulses to the tree. The observed "thinning" did not affect the thick main branches, but exclusively
the smallest shoots. The synapses on these small branches are called excitatory: Signals received there have an arousing effect. This means
that they increase the probability that the neuron will in turn generate
an electrical signal, in other words, that it will "fire." When there
are fewer side branches, the synapses could concentrate in a smaller
area and thereby gain influence, making the neuron easier to excite
(since the synapses are excitatory). "Surprisingly, however, we did
not find an increased density of excitatory synapses," Quatraccioni
points out. "Nevertheless, the affected neurons were more excitable. But
there had to be other reasons." The cause is not to be found in the
delicate twigs, but in the thick main branches. Numerous synapses are
also located there, but of a different type: They have an inhibitory
effect. Any signal received by these synapses prevents the nerve
cell from firing. "The mice initially formed a normal amount of these inhibitory synapses," Quatraccioni explains. "However, after a few days
of life, their density began to decrease. This loss kept progressing."
SLK therefore appears to be important in maintaining normal levels of inhibitory synapses. Without the kinase, the affected neurons become increasingly difficult to inhibit over time. This fits in with the fact
that the researchers were able to detect SLK deficiency in the nerve
cells of brain tissue from epilepsy patients. During epileptic seizures,
whole areas of the brain are overexcited, meaning that the neurons fire
too easily.

Explanation for declining drug efficacy? The findings could also
explain why the effects of the drugs diminish over time in some
sufferers. "Perhaps this effect is not due to resistance to the
drugs, but to the progressive loss of the inhibitory synapses," says
Prof. Dr. Susanne Schoch McGovern. The findings therefore provide new
insights into how the disease develops.

They could also have therapeutic relevance: "We often try
to prevent neuronal overexcitation with drugs that stimulate
inhibitory synapses," explains Schoch McGovern. "This might be the
wrong strategy in the case of an SLK deficiency: At some point,
there are so few inhibitory synapses left that this no longer
works. It is probably more promising in these patients to intervene
on the excitatory side, that is, to inhibit the excitatory synapses." ========================================================================== Story Source: Materials provided by University_of_Bonn. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. Susanne Schoch, Anne Quatraccioni, Barbara K. Robens, Robert
Maresch,
Karen M.J. van Loo, Silvia Cases-Cunillera, Tony Kelly, Thoralf
Opitz, Valeri Borger, Dirk Dietrich, Julika Pitsch, Heinz Beck,
Albert J.

Becker. Ste20-like Kinase Is Critical for Inhibitory Synapse
Maintenance and Its Deficiency Confers a Developmental
Dendritopathy. The Journal of Neuroscience, 2021; 41 (39): 8111
DOI: 10.1523/JNEUROSCI.0352-21.2021 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/10/211001082629.htm

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