Sex as a biological variable in the pathology and pharmacology of neurodegenerative and neurovascular diseases

Honarpisheh, Pedram; McCullough, Louise D.

doi:10.1111/bph.14675

Cited by 36 publications

(23 citation statements)

References 160 publications

(173 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On the sidelines of the main results that emerged from our study, we report for the first time a sex-related different expression of auto/mitophagic biomarkers in patients affected by VAD. Females and males have different incidence and symptom presentation of both dementia and vascular diseases 35,36 . Moreover, sex differences in autophagic mechanisms have been proposed as a contributory factor to female vulnerability in AD 37 .…”

Section: Discussionmentioning

confidence: 99%

Autophagy and mitophagy biomarkers are reduced in sera of patients with Alzheimer’s disease and mild cognitive impairment

Castellazzi

Patergnani

Donadio

et al. 2019

Sci Rep

View full text Add to dashboard Cite

Dementia is a neurocognitive disorder characterized by a progressive memory loss and impairment in cognitive and functional abilities. Autophagy and mitophagy are two important cellular processes by which the damaged intracellular components are degraded by lysosomes. To investigate the contribution of autophagy and mitophagy in degenerative diseases, we investigated the serum levels of specific autophagic markers (ATG5 protein) and mitophagic markers (Parkin protein) in a population of older patients by enzyme-linked immunosorbent assay. Two hundred elderly (≥65 years) outpatients were included in the study: 40 (20 F and 20 M) with mild-moderate late onset Alzheimer’s disease (AD); 40 (20 F and 20 M) affected by vascular dementia (VAD); 40 with mild cognitive impairment (MCI); 40 (20 F and 20 M) with “mixed” dementia (MD); 40 subjects without signs of cognitive impairment were included as sex-matched controls. Our data indicated that, in serum samples, ATG5 and Parkin were both elevated in controls, and that VAD compared with AD, MCI and MD (all p < 0.01). Patients affected by AD, MD, and MCI showed significantly reduced circulating levels of both ATG5 and Parkin compared to healthy controls and VAD individuals, reflecting a significant down-regulation of autophagy and mitophagy pathways in these groups of patients. The measurement of serum levels of ATG5 and Parkin may represent an easily accessible diagnostic tool for the early monitoring of patients with cognitive decline.

show abstract

Section: Discussionmentioning

confidence: 99%

Autophagy and mitophagy biomarkers are reduced in sera of patients with Alzheimer’s disease and mild cognitive impairment

Castellazzi

Patergnani

Donadio

et al. 2019

Sci Rep

View full text Add to dashboard Cite

show abstract

“…neurodegenerative diseases (Honarpisheh & McCullough, 2019;Pinares-Garcia, Stratikopoulos, Stratikopoulos, Zagato, Loke, & Lee, 2018;Ullah et al, 2019), cardiovascular disease (De Bellis et al 2019), inflammation and hypertension (Sylvester & Brooks, 2019),…”

Section: F I G U R Ementioning

confidence: 99%

Age‐related hearing loss: Why we need to think about sex as a biological variable

Nolan

2020

J of Neuroscience Research

View full text Add to dashboard Cite

It has long been known that age‐related hearing loss (ARHL) is more common, more severe, and with an earlier onset in men compared to women. Even in the absence of confounding factors such as noise exposure, these sexdifferences in susceptibility to ARHL remain. In the last decade, insight into the pleiotrophic nature by which estrogen signaling can impact multiple signaling mechanisms to mediate downstream changes in gene expression and/or elicit rapid changes in cellular function has rapidly gathered pace, and a role for estrogen signaling in the biological pathways that confer neuroprotection is becoming undeniable. Here I review the evidence why we need to consider sex as a biological variable (SABV) when investigating the etiology of ARHL. Loss of auditory function with aging is frequency‐specific and modulated by SABV. Evidence also suggests that differences in cochlear physiology between women and men are already present from birth. Understanding the molecular basis of these sex differences in ARHL will accelerate the development of precision medicine therapies for ARHL.

show abstract

“…Even though sex differences in the epidemiology of cerebrovascular disorders are well-known (Honarpisheh and McCullough, 2019), and the susceptibility of the nervous tissue to SD may be modulated by sex (Adámek and Vyskočil, 2011), this variable has not been evaluated here.…”

Section: Discussionmentioning

confidence: 99%

Aging Impairs Cerebrovascular Reactivity at Preserved Resting Cerebral Arteriolar Tone and Vascular Density in the Laboratory Rat

Bálint

Puskás

Menyhárt

et al. 2019

Front. Aging Neurosci.

View full text Add to dashboard Cite

The age-related (mal)adaptive modifications of the cerebral microvascular system have been implicated in cognitive impairment and worse outcomes after ischemic stroke. The magnitude of the hyperemic response to spreading depolarization (SD), a recognized principle of ischemic lesion development has also been found to be reduced by aging. Here, we set out to investigate whether the SD-coupled reactivity of the pial arterioles is subject to aging, and whether concomitant vascular rarefaction may contribute to the age-related insufficiency of the cerebral blood flow (CBF) response. CBF was assessed with laser-speckle contrast analysis (LASCA), and the tone adjustment of pial arterioles was followed with intrinsic optical signal (IOS) imaging at green light illumination through a closed cranial window created over the parietal cortex of isoflurane-anesthetized young (2 months old) and old (18 months old) male Sprague–Dawley rats. Global forebrain ischemia and later reperfusion were induced by the bilateral occlusion and later release of both common carotid arteries. SDs were elicited repeatedly with topical 1M KCl. Pial vascular density was measured in green IOS images of the brain surface, while the density and resting diameter of the cortical penetrating vasculature was estimated with micro-computed tomography of paraformaldehyde-fixed cortical samples. Whilst pial arteriolar dilation in response to SD or ischemia induction were found reduced in the old rat brain, the density and resting diameter of pial cortical vessels, and the degree of SD-related oligemia emerged as variables unaffected by age in our experiments. Spatial flow distribution analysis identified an age-related shift to a greater representation of higher flow ranges in the reperfused cortex. According to our data, impairment of functional arteriolar dilation, at preserved vascular density and resting vascular tone, may be implicated in the age-related deficit of the CBF response to SD, and possibly in the reduced efficacy of neurovascular coupling in the aging brain. SD has been recognized as a potent pathophysiological contributor to ischemic lesion expansion, in part because of the insufficiency of the associated CBF response. Therefore, the age-related impairment of cerebral vasoreactivity as shown here is suggested to contribute to the age-related acceleration of ischemic lesion development.

show abstract

Sex as a biological variable in the pathology and pharmacology of neurodegenerative and neurovascular diseases

Cited by 36 publications

References 160 publications

Autophagy and mitophagy biomarkers are reduced in sera of patients with Alzheimer’s disease and mild cognitive impairment

Autophagy and mitophagy biomarkers are reduced in sera of patients with Alzheimer’s disease and mild cognitive impairment

Age‐related hearing loss: Why we need to think about sex as a biological variable

Aging Impairs Cerebrovascular Reactivity at Preserved Resting Cerebral Arteriolar Tone and Vascular Density in the Laboratory Rat

Contact Info

Product

Resources

About