Researchers investigate connection between loss of motivation and
Alzheimer's disease progression
Date:
April 27, 2022
Source:
Indiana University School of Medicine
Summary:
Researchers are studying why neuropsychiatric symptoms, such
as apathy and irritability, appear in most Alzheimer's disease
patients before the onset of memory loss.
FULL STORY ========================================================================== Researchers from Indiana University School of Medicine are studying why neuropsychiatric symptoms, such as apathy and irritability, appear in
most Alzheimer's disease patients before the onset of memory loss.
==========================================================================
The study, led by Yao-Ying Ma, MD, PhD, assistant professor of
pharmacology and toxicology, was recently featured in the publication
Molecular Psychiatry. The team of researchers identified a receptor in
the brain that leads to a loss of neurons and synaptic structure when
used in an Alzheimer's disease model.
The investigation focused on the nucleus accumbens, a critical brain
region processing motivation. Located in the ventral striatum, this
region is not studied much among Alzheimer's disease researchers, Ma
said; it's mainly researched to understand motivational and emotional processes. Previous studies, Ma said, have shown that the volume of
nucleus accumbens, like the cortical and hippocampal regions in the brain,
is reduced in adults with Alzheimer's disease.
Ma, who is relatively new to the field of Alzheimer's disease research,
has a background in drug addiction studies and synaptic communication --
the process by which neurons talk to each other in the brain. Some of
the neuropsychiatric symptoms among people who suffer from substance
abuse -- apathy, mood swings, anxiety -- are also found in Alzheimer's
disease patients.
"Even before the onset of cognitive deficits, a significant number of Alzheimer's patients start showing mood swings, and they have a greater
chance to have symptoms of depression," Ma said.
These neuropsychiatric symptoms, however, tend to occur earlier than
memory loss, but no effective treatments are available, Ma said. She
emphasized that there is an urgent need to understand why those symptoms
exist and how they correlate with cognitive deficits. Ma said this
study identified synaptic calcium permeable receptors (CP-AMPARs) in
the nucleus accumbens in an Alzheimer's disease model. The receptor,
which is normally absent in that part of the brain, gives permission
for calcium to enter the neurons. This leads to an overload of calcium,
which leads to a breakdown of its synaptic structure.
In turn, calcium accumulation triggers a cascade of intracellular changes
that can be lethal to the neuron by amplifying calcium overload via a
positive feedback mechanism.
This synaptic loss in the brain causes motivation deficits. Knowing
this, Ma said that targeting these receptors in the brain and blocking
them could prevent or delay the onset of Alzheimer's disease associated neuropsychiatric symptoms, and ultimately cognitive deficits.
"If we can postpone the pathological progression in one of the affected
areas, like the nucleus accumbens," Ma said, "that may delay pathological changes in other regions."
========================================================================== Story Source: Materials provided by
Indiana_University_School_of_Medicine. Note: Content may be edited for
style and length.
========================================================================== Journal Reference:
1. Changyong Guo, Di Wen, Yihong Zhang, Richie Mustaklem, Basil
Mustaklem,
Miou Zhou, Tao Ma, Yao-Ying Ma. Amyloid-b oligomers in
the nucleus accumbens decrease motivation via insertion of
calcium-permeable AMPA receptors. Molecular Psychiatry, 2022;
DOI: 10.1038/s41380-022-01459-0 ==========================================================================
Link to news story:
https://www.sciencedaily.com/releases/2022/04/220427115750.htm
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