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Sexual Dimorphism in Neurological Diseases: From Molecular Basis to Therapy
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Sexual Dimorphism in Neurological Diseases: From Molecular Basis to Therapy

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 (15 February 2023) | Viewed by 7557

Special Issue Editor

Dr. Joana Gonçalves

E-Mail Website1 Website2
Guest Editor
1. Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), University of Coimbra, 3000-548 Coimbra, Portugal
2. Institute for Nuclear Sciences Applied to Health (ICNAS), University of Coimbra, 3000-548 Coimbra, Portugal
Interests: neurodevelopmental disorders; gestational nutrition; sex dimorphism; excitation/inhibition balance; animal behavior

Special Issue Information

Dear Colleagues,

Neurological disorders, including multiple sclerosis, migraine, depression, autism spectrum disorder, etc., show strong sex differences in their incidence and disease manifestation. In recent years, the importance of biological sex as a vital factor determining underlying mechanisms of disease and cognitive vulnerability has been substantiated with a direct impact on both the diagnosis and therapeutic response. Indeed, research conducted in this field offers the promise of developing more personalized treatments for both males and females. Accumulating evidence suggests a complex mechanistic scenario with a genetic predisposition and endocrine and environmental factors as interacting components governing diseases’ onset, progression, and severity.

Therefore, sex differences in brain organization and mechanisms, and consequently in behavior, may explain differential disease vulnerability between males and females.

With this in mind, we would like to invite the submission of reviews and original articles addressing the latest achievements in our understanding the mechanisms underlying sex differences in neurological conditions (both in neurodegenerative disorders and in neurodevelopmental disorders), as well as possible sex-targeted therapies for brain diseases.

Dr. Joana Gonçalves
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

  • sex dimorphism
  • neurodegenerative disorders
  • neurodevelopmental disorders
  • neurophysiology
  • neuroimaging
  • neurotransmitter metabolism
  • gut-brain axis
  • neurostimulation
  • sex-targeted therapies

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Published Papers (2 papers)

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Research

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29 pages, 9090 KiB  
Article
Effects of MgSO4 Alone or Associated with 4-PBA on Behavior and White Matter Integrity in a Mouse Model of Cerebral Palsy: A Sex- and Time-Dependent Study
by Lou Legouez, Bérénice Le Dieu-Lugon, Shérine Feillet, Gaëtan Riou, Melissa Yeddou, Thibault Plouchart, Nathalie Dourmap, Marie-Anne Le Ray, Stéphane Marret, Bruno J. Gonzalez and Carine Cleren
Int. J. Mol. Sci. 2022, 23(24), 15947; https://doi.org/10.3390/ijms232415947 - 15 Dec 2022
Cited by 1 | Viewed by 2170
Abstract
Cerebral palsy (CP) is defined as permanent disorders of movement and posture. Prematurity and hypoxia–ischemia (HI) are risk factors of CP, and boys display a greater vulnerability to develop CP. Magnesium sulfate (MgSO4) is administered to mothers at risk of preterm [...] Read more.
Cerebral palsy (CP) is defined as permanent disorders of movement and posture. Prematurity and hypoxia–ischemia (HI) are risk factors of CP, and boys display a greater vulnerability to develop CP. Magnesium sulfate (MgSO4) is administered to mothers at risk of preterm delivery as a neuroprotective agent. However, its effectiveness is only partial at long term. To prolong MgSO4 effects, it was combined with 4-phenylbutyrate (4-PBA). A mouse model of neonatal HI, generating lesions similar to those reported in preterms, was realized. At short term, at the behavioral and cellular levels, and in both sexes, the MgSO4/4-PBA association did not alter the total prevention induced by MgSO4 alone. At long term, the association extended the MgSO4 preventive effects on HI-induced motor and cognitive deficits. This might be sustained by the promotion of oligodendrocyte precursor differentiation after HI at short term, which led to improvement of white matter integrity at long term. Interestingly, at long term, at a behavioral level, sex-dependent responses to HI were observed. This might partly be explained by early sex-dependent pathological processes that occur after HI. Indeed, at short term, apoptosis through mitochondrial pathways seemed to be activated in females but not in males, and only the MgSO4/4-PBA association seemed to counter this apoptotic process. Full article
(This article belongs to the Special Issue Sexual Dimorphism in Neurological Diseases: From Molecular Basis to Therapy)
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Review

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25 pages, 1894 KiB  
Review
Sex Differences in Tryptophan Metabolism: A Systematic Review Focused on Neuropsychiatric Disorders
by Mariana Lapo Pais, João Martins, Miguel Castelo-Branco and Joana Gonçalves
Int. J. Mol. Sci. 2023, 24(6), 6010; https://doi.org/10.3390/ijms24066010 - 22 Mar 2023
Cited by 14 | Viewed by 4245
Abstract
Tryptophan (Tryp) is an essential amino acid and the precursor of several neuroactive compounds within the central nervous system (CNS). Tryp metabolism, the common denominator linking serotonin (5-HT) dysfunctions and neuroinflammation, is involved in several neuropsychiatric conditions, including neurological, neurodevelopmental, neurodegenerative, and psychiatric [...] Read more.
Tryptophan (Tryp) is an essential amino acid and the precursor of several neuroactive compounds within the central nervous system (CNS). Tryp metabolism, the common denominator linking serotonin (5-HT) dysfunctions and neuroinflammation, is involved in several neuropsychiatric conditions, including neurological, neurodevelopmental, neurodegenerative, and psychiatric diseases. Interestingly, most of those conditions occur and progress in a sex-specific manner. Here, we explore the most relevant observations about the influence of biological sex on Tryp metabolism and its possible relation to neuropsychiatric diseases. Consistent evidence suggests that women have a higher susceptibility than men to suffer serotoninergic alterations due to changes in the levels of its precursor Tryp. Indeed, female sex bias in neuropsychiatric diseases is involved in a reduced availability of this amino acid pool and 5-HT synthesis. These changes in Tryp metabolism could lead to sexual dimorphism on the prevalence and severity of some neuropsychiatric disorders. This review identifies gaps in the current state of the art, thus suggesting future research directions. Specifically, there is a need for further research on the impact of diet and sex steroids, both involved in this molecular mechanism as they have been poorly addressed for this topic. Full article
(This article belongs to the Special Issue Sexual Dimorphism in Neurological Diseases: From Molecular Basis to Therapy)
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