Understanding the Role of Perineuronal Nets in Tumor-Related Seizures

A recent article, “Perineuronal nets decrease membrane capacitance of peritumoral fast spiking interneurons in a model of epilepsy,” aimed to gain a better understanding of the role of perineuronal nets in tumor-related seizures.

Purpose 

• Seizures are common in people with brain tumors. These seizures are often refractory, or do not respond, to existing anti-epileptic drugs.
• We have covered basics regarding tumor-related seizures on epilepsy.com previously.
  • Understanding Brain Tumor-related Epilepsy
  • Better Management of Brain Tumor-related Epilepsy
• Neurons in the brain are constantly maintained under a finely-tuned balance of excitation and inhibition. 
  • Glutamate is the excitatory neurotransmitter. Gamma amino butyric acid (GABA) is an inhibitory neurotransmitter, meaning it causes inhibition or decreases neural activity. 
• There is evidence that seizures (and tumor-related seizures specifically) are caused by an imbalance between the excitatory and the inhibitory neurotransmitter systems in the brain.
• In this study, the authors explored unique structured called perineuronal nets (PNN). These condensed, matrix-like assemblies are critical to stabilize neurons.
  • Another reason for studying PNNs is that a subtype of GABAergic neurons called parvalbumin-expressing fast spiking interneurons are associated with PNNs.

Description of Study

• Tumor-related seizures were simulated by implanting patient-derived tumor tissue into brains of experimental mice.
• Electrophysiology was used to measure electrical activity of neurons in these mice.
• A technique called immunohistochemistry was used to visualize neurons under the microscope.

Summary of Study Findings

• Mice with implanted patient-derived tumor cells showed a loss of parvalbumin positive neurons. 
• Immunohistochemistry showed there was a breakdown of PNNs in mice with brain tumors.
• Breakdown of PNNs was found to be due to specific enzymes (called proteases) that were released by the tumor.
• The area around the tumor, called peritumoral tissue, had an imbalance between excitatory and inhibitory neurotransmission, as shown by electrophysiological experiments.

What does this mean? 

• Up until now, the role of PNNs in epilepsy was not clear. 
• In this paper, the scientists were able to successfully show that PNNs can be involved in tumor-related seizures.
• Future experiments will be needed to examine the role of PNNs for seizures due to other causes and whether restoring the PNN can help decrease (or even get rid of) seizures.