Study shows that intranasal Rx halts memory decay in experimental
Alzheimer's model

Date:
March 21, 2022
Source:
Louisiana State University Health Sciences Center
Summary:
A research collaboration has found that applying specialized pro-
resolving lipid mediators intranasally arrested memory loss and
brain degeneration in an experimental model of Alzheimer's Disease
(AD).



FULL STORY ==========================================================================
A research collaboration between scientists at LSU Health New Orleans and
the Karolinska Institutet in Sweden has found that applying specialized
pro- resolving lipid mediators intranasally arrested memory loss and brain degeneration in an experimental model of Alzheimer's Disease (AD). The
results are published in the Nature journal, Communications Biology.


========================================================================== Neuroinflammation is a hallmark of neurodegenerative disorders,
including Alzheimer's Disease. Specialized pro-resolving lipid
mediators are bioactive compounds composed of fatty acids like omega-3
or their derivatives that resolve inflammation. Neuroprotectin D1 (NPD1), discovered by Nicolas Bazan, MD, PhD, Boyd Professor and Director of the
LSU Health New Orleans Neuroscience Center of Excellence, and colleagues
is one. Previous studies by the Bazan lab demonstrated that NPD1 is
protective in experimental stroke as well as retinal damage and that it
is in short supply in the memory area of the brains from AD donors.

Resolving inflammation is a complex process involving mediators, cell
subtypes and communication pathways. Response includes cell communications
that order the activation of protective, pro-survival mechanisms and
silence pro- inflammatory signaling pathways. Specialized pro-resolving
lipid mediators such as NPD1 are the key signaling molecules in the
process.

The paper discloses solid data on microglial activation, pro-inflammatory signaling, chronic inflammation and neuronal damage in Alzheimer's
disease. The study uses the AppNL-G-F/NL-G-F mouse model for AD. The
paper extensively studied amyloid load, cognition, neuronal network oscillations, glial activation, receptors and inflammatory factors.

The authors conclude that the noninvasive administration route, intranasal delivery, of biologically active lipid messengers opens avenues for
therapeutic exploration for AD and other neurodegenerative diseases.

"AD lacks prevention or cure and exerts a horrendous toll on patients
and their families due to crippling progression and devastating adverse events," notes Dr. Bazan, who led the research at LSU Health. "Millions
of Americans currently suffer from AD, and the number is expected to
escalate rapidly in the coming years." Bazan has been collaborating with Marianne Schultzberg, Senior Professor of Clinical Neuroscience at the Department of Neurobiology, Care Sciences and Society at the Karolinska Institutet (KI). Projects include looking at the novel signals that
protect the brain in the cerebral spinal fluid (CSF) of the early stages
of Alzheimer's disease.

"This productive collaboration is uncovering important aspects of early
stages of Alzheimer's Disease, and the novel evolving mechanisms are
promising paths for innovative therapies like the one disclosed in the
current paper," says Professor Schultzberg.

According to the National Institute on Aging, Alzheimer's disease is
currently ranked as the seventh leading cause of death in the United
States and is the most common cause of dementia among older adults.

Other members of the LSU Health New Orleans research team include
Drs. Khanh V.

Do, Bokkyoo Jun and Megan L. Cothern. Ceren Emre, who recently completed
her PhD at the Karolinska Institutet, was co-supervised by Dr. Bazan
and worked at LSU Health New Orleans Neuroscience Center of Excellence
for eight months just before the pandemic.


========================================================================== Story Source: Materials provided by Louisiana_State_University_Health_Sciences_Center. Note: Content may be
edited for style and length.


========================================================================== Journal Reference:
1. Ceren Emre, Luis E. Arroyo-Garci'a, Khanh V. Do, Bokkyoo Jun, Makiko
Ohshima, Silvia Go'mez Alcalde, Megan L. Cothern, Silvia Maioli,
Per Nilsson, Erik Hjorth, Andre' Fisahn, Nicolas G. Bazan, Marianne
Schultzberg. Intranasal delivery of pro-resolving lipid mediators
rescues memory and gamma oscillation impairment in AppNL-G-F/NL-G-F
mice.

Communications Biology, 2022; 5 (1) DOI: 10.1038/s42003-022-03169-3 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/03/220321103809.htm

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