Batten disease may 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, lacking the Cln3 gene.
These mice also lacked a certain type of neuron crucial for building neural networks.
Researchers at Jena University Hospital in Germany were able to link specific disease symptoms or features to the brain abnormalities they observed.
Their study, “Defective synaptic transmission causes disease signs in a mouse model of Juvenile Neuronal Ceroid Lipofuscinosis,” set out to examine how the lack of a functional gene may cause those 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 as in children with Batten disease — the diseased mice showed signs of anxiety.
Since this can be a sign of abnormal synaptic transmission in brain structures dealing with fear, the team measured how well neurons signaled in this area. They found a loss of both activating and inactivating synaptic signals.
A synapse translates an electrical signal in the neuron to a chemical one — 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 appeared to lie in the first step — neurotransmitters were not properly released.
In addition, the mice lacked certain inhibitory neurons — crucial for balancing the neural network processes.
They also found similar changes in the hippocampus — an area linked to memory and learning. Just as in Batten disease patients, mice that lack Cln3 show difficulties with learning and memory.
In the cerebellum — the brain area that takes care of movement coordination — similar defects appeared to cause an abnormal organization of neurons that could be linked to ataxia and other movement abnormalities, again, much as those seen in patients with Batten disease.
In contrast, there were no changes in synaptic transmission or the presence of neurons in the spinal cord of these animals.
While there is little evidence supporting the idea that Batten disease is linked to autoimmune processes, the team suggested that the specific lack of certain neurons warrant an investigation into the possibility that antibodies or immune cells might cause this loss.