Perineuronal net abnormalities in epileptic human tissue

Area of Science:

• Neuroscience
• Extracellular Matrix Biology
• Epilepsy Research

Background:

• Perineuronal nets (PNNs), composed mainly of aggrecan, are crucial for nervous system plasticity and neuron protection.
• PNNs ensheath parvalbumin (PV) interneurons and are implicated in synaptic regulation.
• Understanding PNN alterations in epilepsy is vital for elucidating disease mechanisms.

Purpose of the Study:

• To investigate aggrecan expression within PNNs in human epilepsy specimens.
• To compare PNN alterations in cryptogenic epilepsy and focal cortical dysplasia type II (FCDII).
• To explore the role of PNN remodeling in the epileptogenic process.

Main Methods:

• Analysis of human epilepsy surgical tissues (cryptogenic epilepsy and FCDII) and autoptic controls.
• Immunohistochemistry and confocal microscopy to assess aggrecan distribution.
• RNAscope technique to confirm aggrecan production by pathological neurons.

Main Results:

• Control cortices exhibited a clear aggrecan expression gradient, lost in cryptogenic epilepsy with significant aggrecan loss.
• FCDII showed altered aggrecan labeling in lesions and PNNs around dysmorphic neurons (DNs) with aberrant synaptic formations.
• Perilesional FCDII cortex and cryptogenic cases displayed marked aggrecan loss, while DNs produced aggrecan in FCDII.

Conclusions:

• Etiology-specific PNN remodeling is integral to epileptogenesis.
• Altered PNNs in FCDII suggest a pathogenic role for DNs within the lesion.
• Aggrecan loss in PNNs of cryptogenic and FCDII perilesional areas may be seizure-activity mediated.