Batten disease can be caused by the loss of synaptic connections between neurons in the brain, according to a study that detailed abnormalities in the brains of mice, devoid of Cln3 uncomfortable.
These mice also lacked a certain type of neuron crucial for building neural networks.
Researchers at the Jena University Hospital in Germany were able to link specific symptoms or characteristics of the disease to the brain abnormalities they observed.
Their study, “Defective synaptic transmission causes signs of disease in a mouse model of juvenile neuronal ceroid lipofuscinosis“, set out to examine how the lack of a functioning gene can cause these many features, including visual loss, motor and cognitive decline, and psychiatric symptoms.
Using a number of methods, they compared different aspects of mice lacking Cln3 to normal animals. Results, published in the journal eLife, showed that, just like in children with Batten disease, sick mice showed signs of anxiety.
Since this may be a sign of abnormal synaptic transmission in brain structures dealing with fear, the team measured the quality of neuron signaling in this area. They found a loss of synaptic activation and inactivation signals.
A synapse translates an electrical signal in the neuron into a chemical signal – a neurotransmitter is released from one neuron and binds to receptors on the other neuron making up a synapse. The team noted that the fault seemed to lie in the first stage – the neurotransmitters were not being released properly.
In addition, the mice lacked certain inhibitory neurons, crucial for balancing neural network processes.
They also found similar changes in the hippocampus, an area related to memory and learning. As in patients with Batten disease, mice lacking Cln3 show learning and memory difficulties.
In the cerebellum – the area of ​​the brain that takes care of the coordination of movement – similar defects appeared to cause abnormal organization of neurons which could be linked to ataxia and other movement abnormalities, again, as did those seen in patients with Batten disease.
In contrast, there was no change in synaptic transmission or the presence of neurons in the spinal cord of these animals.
While there is little evidence to support the idea that Batten disease is linked to autoimmune processes, the team suggested that the specific lack of certain neurons warrants investigation into the possibility of antibodies or cells. immune systems can cause this loss.
