Analysing molecular mechanisms behind cognition

18th January 2017
Posted By : Enaie Azambuja
Analysing molecular mechanisms behind cognition

EU-funded scientists have investigated the role of synapse dysfunction in intellectual development and shed more light on the molecular mechanisms behind cognition. The aim MASDUHID (Molecular analysis of synaptic dysfunctions underlying human intellectual disabilities) project was to understand the synaptic molecular dysfunction associated with intellectual disorders, especially non-syndromic intellectual disability (NSID).

Researchers attempted to identify proteins that can be used as pharmacological targets to treat intellectual disability and to determine the extent to which mental disorders can be reverted following birth.

A key resource for the project was mouse models of synaptic proteins associated with NSID, which were already available. These were used to study the synapse as a whole biological system and record the changes it undergoes as a result of disease.

Proteomics and bioinformatics were used to quantitatively analyse the synaptic proteome in control and model animals. By characterising disease related molecular disfunction it could be used to identify pharmological targets and test drugs in animal models for phenotypic recovery.

To achieve these objectives researchers had to develop new techniques that would allow them to look at the synaptic proteome at a much lower scale. Therefore, a microproteomics protocol was developed based on the combined use of laser capture microdissected tissue, biochemical enrichment in synapses of microdissected tissue and mass spectrometry profiling.

These techniques enabled scientists to characterise the postsynaptic proteome of glutamatergic synapses and dentate gyrus in the mouse hippocampus. This enabled those proteins specific to the synapses of these regions to be identified, conferring upon them unique electrophysiological characteristics.

Researchers also studied the model of the autosomal intellectual disability caused by Synaptic Ras GTPase-activating protein 1 (SYNGAP1) haploinsufficiency. They analysed how the hippocampal synaptic proteome responded to reducing SYNGAP protein by half and then recovering it back using a combination of an inducible line and a rescue line of SYNGAP1 conditional knock-out mouse line.

Results from MASDUHID will help to identify the developmental stages from where intellectual recovery is possible. This will be an important factor as pharmacological treatment becomes available.

You must be logged in to comment

Write a comment

No comments

More from University of Barcelona

Sign up to view our publications

Sign up

Sign up to view our downloads

Sign up

Girls in Tech | Catalyst | 2019
4th September 2019
United Kingdom The Brewery, London
DSEI 2019
10th September 2019
United Kingdom EXCEL, London
EMO Hannover 2019
16th September 2019
Germany Hannover
Women in Tech Festival 2019
17th September 2019
United Kingdom The Brewery, London
European Microwave Week 2019
29th September 2019
France Porte De Versailles Paris