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Gender-Related Molecular Mechanism in Neurological Disorders
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Gender-Related Molecular Mechanism in Neurological Disorders

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: closed (28 February 2023) | Viewed by 25855

Special Issue Editor

Dr. Paolo Ragonese

E-Mail Website
Guest Editor
Department of Experimental Medicine and Clinical Neurosciences, Università degli Studi di Palermo, Palermo, Italy
Interests: neurological disorders; neuroepidemiology; multiple scleorsis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Sex differences represent key factors in understanding indicators of pathological mechanisms in neurological diseases. A number of relevant studies have been performed in the past with the aim of investigating how molecular differences related to sex-dependent aspects could shed some light on the aetiology and pathological mechanisms of neurological diseases. For instance, sex differences have been reported in several molecular and biochemical pathways such as oxidative stress. Oxidative stress mechanisms are reported to be higher in men than in women. Hormonal aspects have usually been considered the major drivers of sex differences in neurological diseases; however, more recently, other pathways such as post genomic or epigenomic modification have been found to have a considerable contribution.

The purpose of this Special Issue of IJMS is to explore how sex and gender issues may act in influencing the molecular pathways of neurological disorders and neurodegeneration, in order to understand the pathologies underlying neurodegenerative processes. This Special Issue will cover studies considering animal models, biochemical and/or experimental studies investigating molecular pathways, and reviews exploring molecular and pathogenic mechanisms, revealing new insights into comprehending the pathophysiological modifications associated with the effects of sex and gender on neurological diseases. The issue will highlight how pathologic processes of neurological and neurodegenerative diseases can be determined or modified by sex-dependent issues.

Dr. Paolo Ragonese
Guest Editor

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Keywords

  • gender and sex differences
  • neurological disorders
  • neurodegeneration
  • neuroprotection
  • Parkinson’s disease
  • stroke
  • multiple sclerosis
  • dementia

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Published Papers (6 papers)

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Research

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24 pages, 5909 KiB  
Article
The Effect of the Tau Protein on D. melanogaster Lifespan Depends on GSK3 Expression and Sex
by Ekaterina R. Veselkina, Mikhail V. Trostnikov, Natalia V. Roshina and Elena G. Pasyukova
Int. J. Mol. Sci. 2023, 24(3), 2166; https://doi.org/10.3390/ijms24032166 - 21 Jan 2023
Viewed by 1970
Abstract
The microtubule-associated conserved protein tau has attracted significant attention because of its essential role in the formation of pathological changes in the nervous system, which can reduce longevity. The study of the effects caused by tau dysfunction and the molecular mechanisms underlying them [...] Read more.
The microtubule-associated conserved protein tau has attracted significant attention because of its essential role in the formation of pathological changes in the nervous system, which can reduce longevity. The study of the effects caused by tau dysfunction and the molecular mechanisms underlying them is complicated because different forms of tau exist in humans and model organisms, and the changes in protein expression can be multidirectional. In this article, we show that an increase in the expression of the main isoform of the Drosophila melanogaster tau protein in the nervous system has differing effects on lifespan depending on the sex of individuals but has no effect on the properties of the nervous system, in particular, the synaptic activity and distribution of another microtubule-associated protein, Futsch, in neuromuscular junctions. Reduced expression of tau in the nervous system does not affect the lifespan of wild-type flies, but it does increase the lifespan dramatically shortened by overexpression of the shaggy gene encoding the GSK3 (Glycogen Synthase Kinase 3) protein kinase, which is one of the key regulators of tau phosphorylation levels. This effect is accompanied by the normalization of the Futsch protein distribution impaired by shaggy overexpression. The results presented in this article demonstrate that multidirectional changes in tau expression can lead to effects that depend on the sex of individuals and the expression level of GSK3. Full article
(This article belongs to the Special Issue Gender-Related Molecular Mechanism in Neurological Disorders)
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11 pages, 1426 KiB  
Article
Sex-Dependent Effect of Chronic Piromelatine Treatment on Prenatal Stress-Induced Memory Deficits in Rats
by Natasha Ivanova, Milena Atanasova, Zlatina Nenchovska and Jana Tchekalarova
Int. J. Mol. Sci. 2023, 24(2), 1271; https://doi.org/10.3390/ijms24021271 - 9 Jan 2023
Cited by 2 | Viewed by 1606
Abstract
Prenatal stress impairs cognitive function in rats, while Piromelatine treatment corrects memory decline in male rats with chronic mild stress. In the present study, we aimed to evaluate the effect of chronic treatment with the melatonin analogue Piromelatine on the associative and spatial [...] Read more.
Prenatal stress impairs cognitive function in rats, while Piromelatine treatment corrects memory decline in male rats with chronic mild stress. In the present study, we aimed to evaluate the effect of chronic treatment with the melatonin analogue Piromelatine on the associative and spatial hippocampus-dependent memory of male and female offspring with a history of prenatal stress (PNS). We report that male and female young adult offspring with PNS treated with a vehicle had reduced memory responses in an object recognition test (ORT). However, the cognitive performance in the radial arm maze test (RAM) was worsened only in the male offspring. The 32-day treatment with Piromelatine (20 mg/kg, i.p.) of male and female offspring with PNS attenuated the impaired responses in the ORT task. Furthermore, the melatonin analogue corrected the disturbed spatial memory in the male offspring. While the ratio of phosphorylated and nonphosphorylated adenosine monophosphate response element binding protein (pCREB/CREB) was reduced in the two sexes with PNS and treated with a vehicle, the melatonin analogue elevated the ratio of these signaling molecules in the hippocampus of the male rats only. Our results suggest that Piromelatine exerts a beneficial effect on PNS-induced spatial memory impairment in a sex-dependent manner that might be mediated via the pCREB/CREB pathway. Full article
(This article belongs to the Special Issue Gender-Related Molecular Mechanism in Neurological Disorders)
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25 pages, 3771 KiB  
Article
Age-Dependent Behavioral and Synaptic Dysfunction Impairment Are Improved with Long-Term Andrographolide Administration in Long-Lived Female Degus (Octodon degus)
by Carolina A. Oliva, Daniela S. Rivera, Angie K. Torres, Carolina B. Lindsay, Cheril Tapia-Rojas, Francisco Bozinovic and Nibaldo C. Inestrosa
Int. J. Mol. Sci. 2023, 24(2), 1105; https://doi.org/10.3390/ijms24021105 - 6 Jan 2023
Cited by 1 | Viewed by 2479
Abstract
In Octodon degus, the aging process is not equivalent between sexes and worsens for females. To determine the beginning of detrimental features in females and the ways in which to improve them, we compared adult females (36 months old) and aged females [...] Read more.
In Octodon degus, the aging process is not equivalent between sexes and worsens for females. To determine the beginning of detrimental features in females and the ways in which to improve them, we compared adult females (36 months old) and aged females (72 months old) treated with Andrographolide (ANDRO), the primary ingredient in Andrographis paniculata. Our behavioral data demonstrated that age does not affect recognition memory and preference for novel experiences, but ANDRO increases these at both ages. Sociability was also not affected by age; however, social recognition and long-term memory were lower in the aged females than adults but were restored with ANDRO. The synaptic physiology data from brain slices showed that adults have more basal synaptic efficiency than aged degus; however, ANDRO reduced basal activity in adults, while it increased long-term potentiation (LTP). Instead, ANDRO increased the basal synaptic activity and LTP in aged females. Age-dependent changes were also observed in synaptic proteins, where aged females have higher synaptotagmin (SYT) and lower postsynaptic density protein-95 (PSD95) levels than adults. ANDRO increased the N-methyl D-aspartate receptor subtype 2B (NR2B) at both ages and the PSD95 and Homer1 only in the aged. Thus, females exposed to long-term ANDRO administration show improved complex behaviors related to age-detrimental effects, modulating mechanisms of synaptic transmission, and proteins. Full article
(This article belongs to the Special Issue Gender-Related Molecular Mechanism in Neurological Disorders)
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Review

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16 pages, 1542 KiB  
Review
Cognitive Decline in Early and Premature Menopause
by Marta Sochocka, Julia Karska, Magdalena Pszczołowska, Michał Ochnik, Michał Fułek, Katarzyna Fułek, Donata Kurpas, Justyna Chojdak-Łukasiewicz, Anna Rosner-Tenerowicz and Jerzy Leszek
Int. J. Mol. Sci. 2023, 24(7), 6566; https://doi.org/10.3390/ijms24076566 - 31 Mar 2023
Cited by 27 | Viewed by 9154
Abstract
Early and premature menopause, or premature ovarian insufficiency (POI), affects 1% of women under the age of 40 years. This paper reviews the main aspects of early and premature menopause and their impact on cognitive decline. Based on the literature, cognitive complaints are [...] Read more.
Early and premature menopause, or premature ovarian insufficiency (POI), affects 1% of women under the age of 40 years. This paper reviews the main aspects of early and premature menopause and their impact on cognitive decline. Based on the literature, cognitive complaints are more common near menopause: a phase marked by a decrease in hormone levels, especially estrogen. A premature reduction in estrogen puts women at a higher risk for cardiovascular disease, parkinsonism, depression, osteoporosis, hypertension, weight gain, midlife diabetes, as well as cognitive disorders and dementia, such as Alzheimer’s disease (AD). Experimental and epidemiological studies suggest that female sex hormones have long-lasting neuroprotective and anti-aging properties. Estrogens seem to prevent cognitive disorders arising from a cholinergic deficit in women and female animals in middle age premature menopause that affects the central nervous system (CNS) directly and indirectly, both transiently and in the long term, leads to cognitive impairment or even dementia, mainly due to the decrease in estrogen levels and comorbidity with cardiovascular risk factors, autoimmune diseases, and aging. Menopausal hormone therapy from menopause to the age of 60 years may provide a “window of opportunity” to reduce the risk of mild cognitive impairment (MCI) and AD in later life. Women with earlier menopause should be taken care of by various specialists such as gynecologists, endocrinologists, neurologists, and psychiatrists in order to maintain their mental health at the highest possible level. Full article
(This article belongs to the Special Issue Gender-Related Molecular Mechanism in Neurological Disorders)
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16 pages, 770 KiB  
Review
Gender and Neurosteroids: Implications for Brain Function, Neuroplasticity and Rehabilitation
by Loredana Raciti, Caterina Formica, Gianfranco Raciti, Angelo Quartarone and Rocco Salvatore Calabrò
Int. J. Mol. Sci. 2023, 24(5), 4758; https://doi.org/10.3390/ijms24054758 - 1 Mar 2023
Cited by 19 | Viewed by 3548
Abstract
Neurosteroids are synthesized de novo in the nervous system; they mainly moderate neuronal excitability, and reach target cells via the extracellular pathway. The synthesis of neurosteroids occurs in peripheral tissues such as gonads tissues, liver, and skin; then, because of their high lipophilia, [...] Read more.
Neurosteroids are synthesized de novo in the nervous system; they mainly moderate neuronal excitability, and reach target cells via the extracellular pathway. The synthesis of neurosteroids occurs in peripheral tissues such as gonads tissues, liver, and skin; then, because of their high lipophilia, they cross the blood–brain barrier and are stored in the brain structure. Neurosteroidogenesis occurs in brain regions such as the cortex, hippocampus, and amygdala by enzymes necessary for the in situ synthesis of progesterone from cholesterol. Neurosteroids could be considered the main players in both sexual steroid-induced hippocampal synaptic plasticity and normal transmission in the hippocampus. Moreover, they show a double function of increasing spine density and enhancing long term potentiation, and have been related to the memory-enhancing effects of sexual steroids. Estrogen and progesterone affect neuronal plasticity differently in males and females, especially regarding changes in the structure and function of neurons in different regions of the brain. Estradiol administration in postmenopausal women allowed for improving cognitive performance, and the combination with aerobic motor exercise seems to enhance this effect. The paired association between rehabilitation and neurosteroids treatment could provide a boosting effect in order to promote neuroplasticity and therefore functional recovery in neurological patients. The aim of this review is to investigate the mechanisms of action of neurosteroids as well as their sex-dependent differences in brain function and their role in neuroplasticity and rehabilitation. Full article
(This article belongs to the Special Issue Gender-Related Molecular Mechanism in Neurological Disorders)
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10 pages, 487 KiB  
Review
The Role of Sex Hormones in Pain-Related Conditions
by Onella Athnaiel, Santiago Cantillo, Stephania Paredes and Nebojsa Nick Knezevic
Int. J. Mol. Sci. 2023, 24(3), 1866; https://doi.org/10.3390/ijms24031866 - 18 Jan 2023
Cited by 50 | Viewed by 6452
Abstract
Millions of people are affected by pain-related conditions worldwide. Literature has consistently shown that each individual experiences and perceives pain in a unique manner due to biological, environmental, and cultural factors in which they have been raised. It has been established that biological [...] Read more.
Millions of people are affected by pain-related conditions worldwide. Literature has consistently shown that each individual experiences and perceives pain in a unique manner due to biological, environmental, and cultural factors in which they have been raised. It has been established that biological males and females perceive pain differently and that it may be partially explained by their distinct hormonal profiles since birth, which are only further magnified during puberty. For biological males, high levels of testosterone have shown to increase their pain threshold; and for biological females, estrogen fluctuations have shown to increase pain intensity and perception. However, sex hormones have not been studied in the context of pain treatment or their impact on biochemical pathways involved in pain perception. For this purpose, the transgender community serves as a unique population to investigate the impact of hormone replacement therapy on molecular pathways involved in the perception of pain. The purpose of this review is to explore the biochemistry of hormone replacement in transgender patients who also have other pain-related conditions such as headaches, fibromyalgia, temporomandibular myalgia, and visceral pain. Full article
(This article belongs to the Special Issue Gender-Related Molecular Mechanism in Neurological Disorders)
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