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Our article hub is a great resource for information on managing the symptoms of menopause.

Published by credible scientific, health, and medical organizations, we hope you find these articles useful during your menopause journey.

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Research

The abrupt drop in estrogen levels aligns with neurodegeneration during menopause.

The X factor in neurodegeneration

Journal of Experimental Medicine, 2022

Rhonda Voskuhl | Yuichiro Itoh

ABSTRACT:

Given the aging population, it is important to better understand neurodegeneration in aging healthy people and to address the increasing incidence of neurodegenerative diseases. It is imperative to apply novel strategies to identify neuroprotective therapeutics. The study of sex differences in neurodegeneration can reveal new candidate treatment targets tailored for women and men.

A treatment targeting a distinct estrogen receptor in the brain to prevent neurodegeneration during menopause.

Mind the Gap: Estrogen receptor beta (ERβ) in astrocytes is a therapeutic target to prevent cognitive problems at menopause.

Posted Date: September 29th, 2021

Rhonda Voskuhl | Noriko Itoh | Cassandra Meyer | Yuichiro Itoh | Darian Mangu | Timothy Suen | Ellis Jang | Vincent Tse | Allan MacKenzie-Graham

ABSTRACT:

Aging is a risk factor for cognitive decline and susceptibility to neurodegenerative diseases. Some aspects of aging, like the loss of sex hormones, may be preventable. Menopause is associated with cognitive deficits and brain atrophy. Since standard hormone replacement therapy (HRT) does not mitigate these brain aging outcomes, a gap in knowledge involves understanding brain region-specific, cell-specific, and receptor-specific mechanisms underlying this neurodegeneration. Here, cognitive testing and in vivo magnetic resonance imaging demonstrated that ovarian hormones in female mice at midlife protect against hippocampal-dependent cognitive impairment and dorsal hippocampal atrophy. Further, this neuroprotection in females at midlife is lost in mice with selective deletion of estrogen receptor beta (ERβ) in astrocytes, but not neurons. This preclinical evidence identifies ERβ in astrocytes as a novel therapeutic target to prevent hippocampal-dependent cognitive deficits and reduce posterior hippocampus atrophy in menopausal women, a major unmet need in half the population.

The unique estrogen in PearlPak treatment reduces levels of a neurodegeneration marker in the blood of humans.

Decreased neurofilament light chain levels in estriol-treated multiple sclerosis

Posted Date: September 29th, 2021

Rhonda Voskuhl | Noriko Itoh | Cassandra Meyer | Yuichiro Itoh | Darian Mangu | Timothy Suen | Ellis Jang | Vincent Tse | Allan MacKenzie-Graham

ABSTRACT:

Estrogens have neuroprotective actions depending on estrogen type, dose, and timing in both preclinical models and in women during health and disease. Serum neurofilament light chain is a putative biomarker of neurodegeneration in multiple sclerosis, aging, and other neurodegenerative diseases.

The unique estrogen in PearlPak treatment reduces brain atrophy in humans.

Estriol-mediated neuroprotection in multiple sclerosis localized by voxel-based morphometry

Received: 26 April 2018 | Revised: 5 July 2018 | Accepted: 8 July 2018

Allan MacKenzie-Graham | Jenny Brook | Florian Kurth | Yuichiro Itoh | Cassandra Meyer | Michael J. Montag | He-Jing Wang | Robert Elashoff | Rhonda R. Voskuhl

ABTRACT:

Progressive gray matter (GM) atrophy is a hallmark of multiple sclerosis (MS). Cognitive impairment has been observed in 40%–70% of MS patients and has been linked to GM atrophy. In a phase 2 trial of estriol treatment in women with relapsing–remitting MS (RRMS), higher estriol levels correlated with greater improvement on the paced auditory serial addition test (PASAT) and imaging revealed sparing of localized GM in estriol-treated compared to placebo-treated patients. To better understand the significance of this GM sparing, the current study explored the relationships between the GM sparing and traditional MRI measures and clinical outcomes.

Targeting a distinct estrogen receptor reduces brain atrophy in a pre-clinical model.

Estrogen Treatment Prevents Gray Matter Atrophy in Experimental Autoimmune Encephalomyelitis

Journal of Neuroscience Research 90:1310–1323 (2012)

Allan J. MacKenzie-Graham | Gilda A. Rinek| Andrea Avedisian| Laurie B. Morales| Elizabeth Umeda| Benoit Boulat| Russell E. Jacobs| Arthur W. Toga| Rhonda R. Voskuhl

ABSTRACT:

Gray matter atrophy is an important correlate to clinical disability in multiple sclerosis (MS), and many treatment trials include atrophy as an outcome measure. Atrophy has been shown to occur in experimental autoimmune encephalomyelitis (EAE), the most commonly used animal model of MS. The clinical severity of EAE is reduced in estrogen-reated mice, but it remains unknown whether estrogen treatment can reduce gray matter atrophy in EAE. In this study, mice with EAE were treated with either estrogen receptor (ER)-a ligand or ER-b ligand, and diffusion tensor images (DTI) were collected and neuropathology was performed. DTI showed atrophy in the cerebellar gray matter of vehicle-treated EAE mice compared with healthy controls but not in ER-a or ER-b ligand-treated EAE mice. Neuropathology demonstrated that Purkinje cell numbers were decreased in vehicle-treated EAE mice, whereas neither ER ligand-treated EAE groups showed a decrease. This is the first report of a neuroprotective therapy in EAE that unambiguously prevents gray matter atrophy while sparing a major neuronal cell type. Fractional anisotropy (FA) in the cerebellar white matter was decreased in vehicle- and ER-b ligand-treated but not in ER-a ligand-treated EAE mice. Inflammatory cell infiltration was increased in vehicle- and ER-b ligand-treated but not in ER-a ligand-treated EAE mice. Myelin staining was decreased in vehicle-treated EAE mice and was spared in both ER ligand-treated groups. This is consistent with decreased FA as a potential biomarker for inflammation rather than myelination or axonal damage in the cerebellum in EAE.

Targeting a distinct estrogen receptor in the brain restores cognitive function in a pre-clinical model.

Estriol preserves synaptic transmission in the hippocampus during autoimmune demyelinating disease.

www.laboratoryinvestigation.org August 2012

Marina O. Ziehn | Andrea A. Avedisian | Shannon M. Dervin | Thomas J. O’Dell | Rhonda R. Voskuhl

ABSTRACT:

Cognitive deficits occur in over half of multiple sclerosis patients, with hippocampal-dependent learning and memory
commonly impaired. Data from in vivo MRI and post-mortem studies in MS indicate that the hippocampus is targeted.
However, the relationship between structural pathology and dysfunction of the hippocampus in MS remains unclear.
Hippocampal neuropathology also occurs in experimental autoimmune encephalomyelitis (EAE), the most commonly
used animal model of MS. Although estrogen treatment of EAE has been shown to be anti-inflammatory and neuroprotective in the spinal cord, it is unknown if estrogen treatment may prevent hippocampal pathology and dysfunction. In the current study, we examined excitatory synaptic transmission during EAE and focused on pathological changes in synaptic protein complexes known to orchestrate functional synaptic transmission in the hippocampus. We then
determined if estriol, a candidate hormone treatment, was capable of preventing functional changes in synaptic transmission and corresponding hippocampal synaptic pathology.

Targeting a distinct estrogen receptor induces repair in the brain in a pre-clinical model.

Gene expression in oligodendrocytes during remyelination reveals cholesterol homeostasis as a therapeutic target in multiple sclerosis

Rhonda R. Voskuhl | Noriko Itoh| Alessia Tassoni| Macy Akiyo Matsukawa| Emily Ren| Vincent Tse| Ellis Jang| Timothy Takazo Suen| and Yuichiro Itoh

ABSTRACT:

Regional differences in neurons, astrocytes, oligodendrocytes, and microglia exist in the brain during health, and regional differences in the transcriptome may occur for each cell type during neurodegeneration. Multiple sclerosis (MS) is multifocal, and regional differences in the astrocyte transcriptome occur in experimental autoimmune encephalomyelitis (EAE), an MS model. MS and EAE are characterized by inflammation, demyelination, and axonal damage, with minimal remyelination. Here, RNA-sequencing analysis of MS tissues from six brain regions suggested a focus on oligodendrocyte lineage cells (OLCs) in corpus callosum. Olig1-RiboTag mice were used to determine the translatome of OLCs in vivo in corpus callosum during the remyelination phase of a chronic cuprizone model with axonal damage. Cholesterol-synthesis gene pathways dominated as the top up-regulated pathways in OLCs during remyelination. In EAE, remyelination was induced with estrogen receptor-β (ERβ) ligand treatment, and up-regulation of cholesterol-synthesis gene expression was again observed in OLCs. ERβ-ligand treatment in the cuprizone model further increased cholesterol synthesis gene expression and enhanced remyelination. Conditional KOs of ERβ in OLCs demonstrated that increased cholesterol-synthesis gene expression in OLCs was mediated by direct effects in both models. To address this direct effect, ChIP assays showed binding of ERβ to the putative estrogen response element of a key cholesterol-synthesis gene (Fdps). As fetal OLCs are exposed in utero to high levels of estrogens in maternal blood, we discuss how remyelinating properties of estrogen treatment in adults during injury may recapitulate normal developmental myelination through targeting cholesterol homeostasis in OLCs.

In The News

Published July 13th, 2023 in Axios Science

Investigating the XY Factor in Disease

Doctors and scientists have long recognized certain diseases affect men and women differently, yet the dosage and design of drugs remain the same.

In this newest article with contributing information from PearlPAK inventor and UCLA neuroscientist Dr. Rhonda Voskuhl, learn how scientists are beginning to understand how sex chromosomes and hormones affect people’s risk for certain diseases – and whether the biology behind those differences can be harnessed to improve treatments.

May 1, 2023, Published in UCLA Newsroom

Dr. Rhonda Voskuhl receives grant to discover neuroprotective treatments for MS

Last week it was announced that Dr. Rhonda Voskuhl’s extensive research career in neuroscience has resulted in a $7.3 million Research Program Award from the National Institute of Health.

September 18, 2023, Published on rachelhorneprize.com & ECTRIMS

Dr. Rhonda Voskuhl, inventor of PearlPAK™ by CleopatraRX, named winner of the Rachel Horne Prize for Women’s Research in MS.

In a groundbreaking recognition of her remarkable contributions to multiple sclerosis (MS) research, Dr. Rhonda Voskuhl, a distinguished neurologist and researcher at the Brain Research Institute at the University of California, Los Angeles (UCLA), has been awarded the inaugural Rachel Horne Prize for Women’s Research in MS.