Impact of sex differences and gender specificity on behavioral characteristics and pathophysiology of neurodegenerative disorders

Ullah, Mohammad Fahad; Ahmad, Aamir; Bhat, Showket H.; Abuduhier, Faisel M.; Barreto, George E.; Ashraf, Ghulam Md

doi:10.1016/j.neubiorev.2019.04.003

Cited by 73 publications

(53 citation statements)

References 154 publications

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“…Sex differences seem to be a critical factor in the development of several neurodegenerative diseases such as Alzheimer's Disease, Huntington's Disease, and PD. PD affects more men than women and the male sex resulted to be one of the most remarkable PD risk factors [34]. In light of this, Weiduschat and colleagues explored mitochondrial function in PD in order to find potential differences regarding sex and they found higher ATP values in the striatum of women patients as well as in the temporoparietal grey matter contralateral to the more affected body size.…”

Section: Resting-state 31 P-mrsmentioning

confidence: 99%

In Vivo Mitochondrial Function in Idiopathic and Genetic Parkinson’s Disease

2019

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Parkinson's disease (PD) is associated with brain mitochondrial dysfunction. High-energy phosphates (HEPs), which rely on mitochondrial functioning, may be considered potential biomarkers for PD. Phosphorus magnetic resonance spectroscopy ( 31 P-MRS) is a suitable tool to explore in vivo cerebral energetics. We considered 10 31 P-MRS studies in order to highlight the main findings about brain energetic compounds in patients affected by idiopathic PD and genetic PD. The studies investigated several brain areas such as frontal lobes, occipital lobes, temporoparietal cortex, visual cortex, midbrain, and basal ganglia. Resting-state studies reported contrasting results showing decreased as well as normal or increased HEPs levels in PD patients. Functional studies revealed abnormal PCr + βATP levels in PD subjects during the recovery phase and abnormal values at rest, during activation and recovery in one PD subject with PINK1 gene mutation suggesting that mitochondrial machinery is more impaired in PD patients with PINK1 gene mutation. PD is characterized by energetics impairment both in idiopathic PD as well as in genetic PD, suggesting that mitochondrial dysfunction underlies the disease. Studies are still sparse and sometimes contrasting, maybe due to different methodological approaches. Further studies are needed to better assess the role of mitochondria in the PD development.

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Section: Resting-state 31 P-mrsmentioning

confidence: 99%

In Vivo Mitochondrial Function in Idiopathic and Genetic Parkinson’s Disease

2019

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“…Importantly, our results highlight important gender differences in UA levels and the utility for UA to serve as a potential disease biomarker. There are a number of genderrelated differences that have been reported in neurodegenerative diseases (Ullah et al, 2019), which have made it necessary to incorporate sex as a biological factor in experimental and clinical studies. Importantly, such studies have enhanced the current understanding of the impact of sexual dimorphism in neurological diseases (Zagni et al, 2016;Ullah et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

“…There are a number of genderrelated differences that have been reported in neurodegenerative diseases (Ullah et al, 2019), which have made it necessary to incorporate sex as a biological factor in experimental and clinical studies. Importantly, such studies have enhanced the current understanding of the impact of sexual dimorphism in neurological diseases (Zagni et al, 2016;Ullah et al, 2019). In our studies, we first found that UA levels were higher in male FIGURE 3 | Gender and age effects of uric acid (UA) in saliva from Huntington's disease (HD) patients and normal controls (NC).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, gender has emerged as another factor that can affect disease outcomes in HD, with women showing worse symptoms and a faster rate of progression (Dorner et al, 2007;Zielonka et al, 2013). In fact, there are several gender-related differences that have been reported in other neurodegenerative diseases as well, which have enhanced our current understanding of the impact of sexual dimorphism in neurological diseases and the implications for preventive and therapeutic outcomes (Zagni et al, 2016;Ullah et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

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Uric Acid as a Potential Peripheral Biomarker for Disease Features in Huntington’s Patients

et al. 2020

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Oxidative stress has long been implicated in the pathophysiology and progression of Huntington's disease (HD). Uric acid (UA) is a naturally occurring antioxidant that is present in the brain and periphery. Growing evidence has implicated UA as a molecular biomarker for several neurodegenerative diseases, most notably Parkinson's disease (PD). In this study, we investigated UA levels in clinical samples from HD patients and normal controls (NCs) and assessed potential relationships between UA levels and disease and clinical data. UA levels were measured in plasma (n = 107) and saliva (n = 178) samples from premanifest (pre-HD) and manifest HD patients and control subjects. Gender effects of UA levels were observed in both biofluids, with male patients showing higher UA levels compared to female patients. Comparisons of UA levels across diagnostic groups, separated by gender, revealed that both plasma and salivary UA levels were significantly lower in female pre-HD and manifest HD patients compared to NCs. Salivary levels of UA were also significantly lower in male manifest HD patients versus controls, but not in plasma. Correlations of peripheral UA levels to clinical data also showed differences according to gender. In male HD patients, both plasma and salivary UA levels were significantly negatively correlated with total functional capacity (TFC), while positive correlations were observed with total motor score (TMS). Female HD patients showed a significant positive correlation between plasma UA levels and TMS, while salivary UA levels from female patients were significantly correlated to disease burden. Finally, in a separate cohort, we show that UA levels are decreased in postmortem prefrontal cortical samples (n = 20) from HD subjects compared to matched controls. These findings suggest that decreased levels of UA in the brains of HD patients can be reflected in peripheral fluids, with salivary measures of UA particularly offering significant promise as a potentially relevant, non-invasive biomarker of disease symptoms and burden. Our findings further highlight the impact of sexual dimorphism in HD pathophysiology.

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“…The de inition of this syndrome underlies a series of movement disorders that ind common denominator in an alteration of the extrapyramidal system and its components responsible for regulating the postural adjustments that accompany the voluntary movement. From a pathophysiological and etiopathogenic point of view, patients with extrapyramidal syndrome can be classi ied as patients with Parkinson's disease or Parkinsonism [3][4][5][6].…”

Section: Introductionmentioning

confidence: 99%

Postural and Kynematic effect of a new custom-made foot insole called “Prodynamic” in a cohort of patients affected by extrapiramidal disease

Falso¹,

Grillo²,

Righetti³

et al. 2019

J Nov Physiother Rehabil

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Background:The use of a custom-made orthotic plantar device is referenced as a true sensor-motor facilitation tool for the control of the postural orthostatic and orthodynamic position in patients with Parkinson's disease.Aim: To outline the postural and kinematic effect of a pro-ergonomic multilayer foot insole versus a custommade carbon-kevlar dynamic foot insole in a cohort of patients affected by extrapyramidal disease. Setting:A rehabilitation institute for the treatment of neurological and orthopaedic gait disorders. Methods:A sample of 8 patients (mean age of 82.6), of whom 4 affected by Parkinson's disease (P) and 4 by Parkinsonism (PS) were recruited for the aim of this study. In line with our inclusion criteria (clinical-functional diagnosis of Parkinson's disease or Parkinsonism, Webster scale ≤ 20, Mini-mental State Examination (MMSE) ≥ 18), the study design developed in 2 times: a. time T1 (or evaluation time), in which recruited patients affected by Parkinson's disease or Parkinsonism were evaluated at the Hospital and Noble Resting House Paolo Richiedei through an accurate functional (Conley scale, Barthel Index scale, Tinetti scale and the Berg Balance Scale), postural evaluation (VPA)and walking examination (VGA, baropodometric evaluation, kinematic gait evaluation through WIVA system); to each group of patients of our study were therefore entrusted 4 foot-insoles, of which 2 synthetic and 2 carbon-kevlar custom-made foot-insoles called PRODYNAMIC; at the end of this step, patients started with our integrated rehabilitative treatment course.b. time T2 (or experimental time; 90 days from T1), a new clinical-instrumental evaluation of each patient was performed, repeating the clinical-functional and instrumental evaluation performed at the time T1 in a specular way; this assessment was performed in FW condition, with personal footwear and previously acquired foot-insoles used during the evaluation at the T1 time.Results: Most of our patients have been able to fi nd benefi t from the use of the plantar orthosis and integrated rehabilitation treatment so as to bring some modifi cations within personal postural attitude, recording an improvement but not uniform change within the sample. The results obtained by comparing the VPA at time T1 and at time T2 explain how patients affected by both clinical forms tend to establish incorrect postural attitudes due to stiffness and appearance of hypertonic plasticity, which become then structured and only partially modifi able. There was a general performance improvement in line with the VGA: within the P.B group, we observed with the use of the Prodynamic insole a partial or even complete normalization of the dynamic heel-contact phase, a better alignment of the COP in its excursion from the 1st to the 2nd rocker phase of the step, a notable facilitation to the inertial thrust in progress in the 3rd and 4th rocker phase, an improvement in the eccentric control of the patellofemoral alignment in the acceptance phase of the so-called load-response in stance and,...

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Impact of sex differences and gender specificity on behavioral characteristics and pathophysiology of neurodegenerative disorders

Cited by 73 publications

References 154 publications

In Vivo Mitochondrial Function in Idiopathic and Genetic Parkinson’s Disease

In Vivo Mitochondrial Function in Idiopathic and Genetic Parkinson’s Disease

Uric Acid as a Potential Peripheral Biomarker for Disease Features in Huntington’s Patients

Postural and Kynematic effect of a new custom-made foot insole called “Prodynamic” in a cohort of patients affected by extrapiramidal disease

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