Scientists gain new understanding of how brain cells talk - which could
help in the treatment of mental health conditions and memory diseases

Date:
October 19, 2021
Source:
University of Nottingham
Summary:
Experts have discovered that reversing the modification of
molecular messages at synapses in the human brain, may contribute
to reversible mental health conditions such as anxiety, and memory
diseases such as dementia.



FULL STORY ========================================================================== Experts from the University of Nottingham have discovered that reversing
the modification of molecular messages at synapses in the human brain,
may contribute to reversible mental health conditions such as anxiety,
and memory diseases such as dementia.


==========================================================================
The findings , published in Molecular Psychiatry,are a major step in our understanding how brain cells communicate, and could help to identify
new treatments for neurological and psychiatric conditions.

The research was led by Dr Helen Miranda Knight in the School of Life
Sciences at the University of Nottingham, along with researchers across
the Schools of Medicine, Life Science, and Bioscience. It was conducted
using the University of Nottingham's state-of-the-art Deep seq, SLIM microscopy, and, Nanoscale and Microscale Research Centre facilities.

Nerve cells in the human brain talk to one another at sites called
synapses, where molecules are released to signal to the next cell. When
people learn or remember things, this signalling is strengthened. When communication between synapses goes wrong, circuits become broken. As
more circuits are lost, this changes how people can think and perform
everyday tasks. This is seen in cognitive disorders, such as forms of
dementia and some mental health conditions.

The function of nerve cells and synapses depends on proteins that are
made using information encoded in genetic material called RNA. It is
thought that RNAs are located exactly where and when they are needed
for synaptic signalling because some kind of synaptic 'tag' labels the
correct active synapse.

Scientists have recently learnt that RNA can have a methyl group/molecule
added to one of the RNA bases which 'marks' the RNA message. Such
adding of methyl groups can influence proteins binding to DNA or RNA
and consequently stop proteins being produced.

This new study shows that RNA marking can be reversed at synapses
and hence may act as a 'synaptic tag'. The findings suggest, that if
disrupted, this could cause synapses and nerve cells to malfunction by influencing the formation of toxic protein clumps.

The researchers used advanced microscopy to examine changes in marked
RNAs in time and location at synapses, and a sequencing technique
to characterise 'marked' RNAs in brain tissue from the hippocampus,
a region of the brain very important for memory formation.

Dr Knight said: "In this new study, we are able to gain a new
understanding of the genomic mechanisms which regulate how nerve cells communicate at synapses.

These genomic mechanisms involve methyl groups being put on RNA
messages and importantly taken off when a synapse is active. The
implications are very important for normal brain function but also for reversible psychiatric mental conditions such as anxiety and addiction disorders and early-stage neurodegenerative diseases such as dementias." ========================================================================== Story Source: Materials provided by University_of_Nottingham. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Braulio Martinez De La Cruz, Robert Markus, Sunir Malla, Maria
Isabel
Haig, Chris Gell, Fei Sang, Eleanor Bellows, Mahmoud Awad Sherif,
Denise McLean, Anbarasu Lourdusamy, Tim Self, Zsuzsanna Bodi,
Stuart Smith, Michael Fay, Ian A. Macdonald, Rupert Fray, Helen
Miranda Knight.

Modifying the m6A brain methylome by ALKBH5-mediated demethylation:
a new contender for synaptic tagging. Molecular Psychiatry, 2021;
DOI: 10.1038/ s41380-021-01282-z ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/10/211019082713.htm

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