• Researchers investigate connection betwe

    From ScienceDaily@1:317/3 to All on Wed Apr 27 22:30:50 2022
    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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