Density of GABAergic neurons are altered in the cerebral cortex of Lafora disease mouse model

Lafora disease (LD) is a progressive neurodegenerative disorder that manifest with myoclonic epilepsy. It may also be considered as a disorder of carbohydrate metabolism because of the formation of Lafora bodies, polyglucosan inclusion in the brain and other tissues due to abnormalities of the proteins laforina or malin. However, underlying mechanisms of neurodegeneration in this disorder are poorly understood.
The aim of our study is to know the underlying mechanisms of neurodegeneration in the cerebral cortex of LD.
We have utilized two different mouse models for LD, the knockout laforin and knockout malin. We use different antibodies to quantify the number of GABAergic cortical neurons (GAD67), expression of neurotrophins such as BDNF and NGF, p75NTR neurotrophin receptor, ubiquitin and Tau protein.

We found that the density of GABAergic neurons was decreased in the cerebral cortex of LD. This decline was to 1-month-old mice, just when we described the first Lafora body accumulation in the cytoplasm of neurons. Also, we showed a decrease of neurotrophin expression in the cerebral cortex and increase of p75NTR expression, and an increase of ubiquitination process and collapse of Tau protein inside of cytoplasm of neurons.
These findings suggest an overall increase in excitatory connectivity in the cerebral cortex of LD due to loss of inhibitory neurons. We propose that these changes contribute to epileptogenicity in this disease. Also, we propose that the damage in neurotrophin signalling could contribute to the neurodegenerative mechanisms described in the pathology of LD

No relevant conflicts of interest declared.