# Lamin A/C regulates cerebellar granule cell maturation

## TL;DR

This study shows that Lamin A/C influences the maturation of cerebellar granule cells and protects them from excitotoxicity and inflammation.

## Contribution

The first investigation of Lamin A/C's role in neuronal maturation using multiple rat, mouse, and human models.

## Key findings

- Lamin A/C down-regulation protects neurons from glutamate-induced excitotoxicity.
- Reduced Lamin A/C correlates with inhibited calcium influx and lower pro-inflammatory cytokine activity.
- Findings support Lamin A/C's role in neural development and neurodegenerative disease mechanisms.

## Abstract

Lamin A/C is a nuclear type V intermediate filament protein part of the meshwork structure underlying the inner nuclear membrane (nuclear lamina), which plays numerous roles, including maintenance of nuclear shape, heterochromatin organization, and transcriptional regulation. Our group has demonstrated the role of Lamin A/C in different pathophysiological conditions. Here, we investigated for the first time how Lamin A/C affects neuronal maturation in rat cerebellar granule cells (GCs). Primary rat cerebellar GCs where we silenced the Lmna gene constituted our key model; this provided a rather homogeneous cellular system showing a neuronal population in vitro. We then validated our findings in another in vivo murine model with knock-out of the Lmna gene and in an in vitro human neuronal model with silencing of the LMNA gene. We observed across three different models that Lamin A/C down-regulation affects neurons maturation by protecting the cells from glutamate-evoked excitotoxicity and correlates with an inhibition of calcium influxes and a down-regulation of pro-inflammatory cytokine pathways. Consistent with previous findings from our group, this study corroborates that Lamin A/C plays a key role in neural development and opens new significant implications for a better comprehension of the mechanisms involved in neurodegenerative diseases, where changes in the nuclear envelope are linked to neuroinflammatory processes and damage.

The online version contains supplementary material available at 10.1007/s10565-025-10011-z.