Schematic of mice
with dysfunctional and functional Wnt signaling.
Credit: University College London
Memory loss in mice
has been successfully reversed following the discovery of new information about
a key mechanism underlying the loss of nerve connectivity in the brain, say UCL
researchers.
Published today in Current
Biology, the study funded by Alzheimer's Research UK, Parkinson's UK,
Wellcome, MRC and the EU investigated the mechanism driving communication
breakdown in adult brains
– specifically, the loss of connections between nerve cells in the
hippocampus, an area of the brain
that controls learning and memory. The team found Wnt proteins play a key role
in the maintenance of nerve connectivity in the adult brain and could become
targets for new treatments that prevent and restore brain function in neurodegenerative
diseases.
The breakdown of
connections between nerve cells is an early feature of diseases like
Alzheimer's and is known to cause distressing
symptoms like memory and thinking decline, but the biological
processes behind it are poorly understood. Nerve cells are connected at
communication points called
synapses and the
slow degeneration of these connections is an important area of study for
researchers looking to slow or stop Alzheimer's disease.
Lead author,
Professor Patricia Salinas (UCL Cell & Developmental Biology), said:
"Synapses are absolutely critical to everything that our brains do. When
these important communication points are lost, nerve cells cannot exchange
information and this leads to symptoms like memory and thinking problems. The
Wnt pathway is emerging as a key player in the regulation of the formation,
maintenance and function of synapses, and we have provided strong evidence that
the Wnt proteins are also critical for memory.
"Understanding
the role of Wnts in Alzheimer's disease is an important next step, as there is
potential we could target this chain of events with drugs. Preventing or
reversing the disruptions in connectivity and communication between nerve cells
in Alzheimer's would be a huge step forward."
Increasing evidence
suggests that deficiency in Wnt function contributes to disruption of brain
connectivity in Alzheimer's disease and therefore resulting in memory loss. The
team studied the impact of a protein called Dkk1, known to block the action of
Wnts and found at higher levels in people with Alzheimer's, in brain circuits
and memory.
Genetically modified
mice in which Dkk1 can be switched on, disrupting the action of Wnts and its
downstream chain of events were used. To avoid any disruption to normal brain
development driven by Wnts and Dkk1, the researchers waited until the mice were
adults before switching on Dkk1 in an area of the brain important for the
formation of new memories.
When Dkk1 was
switched on in the adult mice, the researchers found the mice had memory
problems, and that this coincided with the presence of fewer synapses between
nerve cells, indicating a communication breakdown. However, when the
researchers switched Dkk1 back off, the mice no longer had memory problems, the
number of synapses increased back to normal levels and brain circuits were
restored.
Dr Simon Ridley,
Director of Research at Alzheimer's Research UK, said: "This study in mice
adds further weight to a growing body of evidence implicating Wnts and its
related proteins to nerve cell connectivity and memory. By understanding
mechanisms driving healthy nerve cells, we can best unpick what happens when
these processes go so wrong.
"This research
sets a solid foundation for future work to explore the role of Wnts in diseases
like Alzheimer's, and this biological process is already a key target being
explored by expert teams in the Alzheimer's Research UK Drug Discovery
Alliance. Researchers are taking huge steps forward in their understanding of
what happens in the brain in health and disease, and we must now capitalise on
these discoveries to deliver effective treatments that can transform
lives."
Journal reference: Current Biology
Provided by: University College London
http://medicalxpress.com/news/2016-09-key-mechanism-brain-memory-revealed.html
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