Early Brain Changes in Huntington’s Disease: New Study Uses Advent Research Materials in Breakthrough Findings

Researchers from the University of Dundee and Cardiff University have used precision metals supplied by Advent Research Materials to study early brain changes in the zQ175 mouse model of Huntington’s disease. Their findings reveal that synaptic dysfunction appears months before behavioural symptoms, providing new insight into how the disease develops and a valuable reference point for future neurodegenerative research.

A new study published in Nature (2025) has mapped the development of Huntington’s disease (HD) symptoms in the zQ175 knock-in mouse, one of the most widely used genetic models for studying the disorder.

The research, led by teams at the University of Dundee and Cardiff University, followed mice from 3 to 13 months of age to track changes in cognition, movement, metabolism, and brain pathology.

Early Synaptic Changes Before Symptoms

Using hippocampal slice electrophysiology, the researchers found that long-term potentiation (LTP) — a fundamental process underpinning learning and memory — was already impaired at just 3 months, before any visible disease symptoms emerged.

This suggests that functional decline in the hippocampus begins early in Huntington’s disease progression, well before the onset of motor or behavioural signs.

Materials Supplied by Advent Research Materials

The electrophysiological recordings that revealed this early deficit relied on high-purity components supplied by Advent Research Materials (Eynsham, UK):

1. Teflon-coated tungsten stimulating electrodes – used to deliver precise electrical stimulation to hippocampal tissue slices.
2. Silver recording and grounding wires – used to measure field excitatory post-synaptic potentials (fEPSPs) with high stability and minimal electrical interference.

These materials were critical in ensuring signal accuracy and repeatability during long-term potentiation (LTP) measurements.

The electrodes and grounding wires formed part of the setup used to stimulate the Schaffer collateral–commissural pathway and record synaptic activity in the CA1 region of the hippocampus — the area responsible for memory formation and plasticity.

By using consistent, research-grade metals from Advent, the team were able to detect subtle declines in synaptic strength that might otherwise have gone unnoticed.

A Timeline of Cognitive, Motor, and Metabolic Decline

The zQ175 mice showed a clear progression that mirrors the human condition:

• 3–4 months: Impaired visuospatial attention
• 6–7 months: Emergence of anxiolytic-like behaviour and reduced fat mass
• 12–13 months: Long-term and spatial memory deficits, together with measurable motor impairments

By one year of age, the mice also displayed brain atrophy and mutant huntingtin protein (mHTT) aggregates in regions including the striatum, hippocampus, and hypothalamus — areas involved in movement, memory, and metabolic control.

Regional Differences in Brain Pathology

When the researchers examined the distribution of huntingtin aggregates, they found marked regional variation.
The striatum showed the highest accumulation, followed by the hippocampus and hypothalamus.
Within the hippocampus, the dentate gyrus was the most affected subregion, while the CA2 area showed relative resistance — reflecting distinct cellular vulnerabilities similar to those seen in human HD brains.

Implications for Huntington’s Research

The results confirm that the zQ175 knock-in mouse accurately models many aspects of Huntington’s disease, from early cognitive changes to later-stage motor and metabolic decline.
Crucially, the discovery that synaptic function deteriorates before visible symptoms or protein aggregation provides an important window for testing neuroprotective treatments.

By supporting electrophysiological precision in this study, Advent Research Materials contributed to research that refines how scientists understand the earliest stages of Huntington’s disease — helping future studies identify where, and when, interventions may have the greatest impact.

Reference:
McLean, F.H. et al. (2025). Development of cognitive, motor, metabolic, and mutant huntingtin aggregation in the zQ175 mouse model of Huntington’s disease. Scientific Reports, 15:34563.
https://doi.org/10.1038/s41598-025-17956-5