Trehalose rescues glial cell dysfunction in striatal cultures from HD R6/1 mice at early postnatal development.

Area of Science:

• Neuroscience
• Cell Biology
• Pharmacology

Background:

• Huntington disease (HD) is characterized by mutant huntingtin (mHTT) aggregation and striatal neuron loss.
• The role of glial cells in HD pathogenesis is not well understood, often considered secondary to neuronal defects.

Purpose of the Study:

• To investigate early-stage glial cell abnormalities in Huntington disease (HD) models.
• To evaluate the protective effects of trehalose on HD glial cells.

Main Methods:

• Analysis of striatal glial cell cultures from postnatal R6/1 mice (HD model) and wild-type littermates.
• Assessment of glial cell characteristics, protein aggregation, and response to oxidative and proteasomal stress.
• Evaluation of trehalose's impact on autophagy, protein clearance, and glial cell function.

Main Results:

• HD glial cells exhibited reactive astrocytes, reduced progenitor cells, increased microglia, and impaired protein quality control (UPS and autophagy deregulation).
• HD glia showed lower glutathione levels and increased susceptibility to insults.
• Trehalose treatment reduced mHTT and alpha-synuclein aggregates, decreased microglia activation, and enhanced astrocyte function and neurotrophic factor secretion.

Conclusions:

• Glial cells undergo significant functional changes early in HD development, contributing to neurodegeneration.
• Trehalose demonstrates therapeutic potential for HD by targeting glial cells to clear protein aggregates and provide neuroprotection.