Analysis of Neurotrophic and Antioxidant Factors Related to Midbrain Dopamine Neuronal Loss and Brain Inflammation in the Cerebrospinal Fluid of the Elderly
Abstract
Midbrain dopamine neuronal loss and neuroinflammation are two phenomena that are associated with brain senescence. Neurotrophic factor changes and oxidative stress could subserve these phenomena. Aging-related brain changes can be well monitored through the cerebrospinal fluid (CSF). The objective was to analyze neurotrophic and oxidative parameters that could be related to midbrain dopamine neuronal loss or brain inflammation in the CSF of elderly subjects: 1) levels of the dopaminotrophic factors BDNF, GDNF, persephin, and neurturin, 2) levels of the proinflammatory factors TGFβ 1 and TGFβ 2; 3) activity of main antioxidant enzymes (catalases, glutathione-peroxidase, glutathione-reductase, glutathione-S-transferases, peroxirredoxins, and superoxide-dismutases), 4) ferritin content, antioxidant protein which reduces reactive free iron, and 5) antioxidant potential of the cerebrospinal fluid. ELISA and PAO tests were used. Subjects were also evaluated clinically, and the group of old subjects with mild cognitive impairment was studied separately. The findings indicate that normal elderly CSF is devoid of changes in either dopaminotrophic or proinflammatory factors. The antioxidant efficacy is slightly reduced with normal aging, through a reduction of glutathione-S-transferase activity in people older than 74 years (p < 0.05). However old people with mild cognitive impairment show reduced BDNF levels, and stronger signs of oxidative stress such as low antioxidant potential and glutathione-S-transferase activity (p < 0.05). To sum up, the present study demonstrates that, in CSF of normal senescence, dopaminotrophic factors and proinflammatory TGF-family ligands are not affected, and antioxidant efficacy is slightly reduced. CSF of elderly subjects with mild cognitive impairment shows more oxidative and trophic changes that are characterized by reduction of BDNF content, glutathione-S-transferase activity, and antioxidant potential.
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Elderly people (>74 years old) are generally characterized by reduced glutathione-S-transferase activity and slightly lower cerebrospinal fluid antioxidant defences compared to younger individuals.
“At brain level, elderly people (>74 years old) are generally characterized by reduced glutathione-S-transferase activity accompanied by slightly lower cerebrospinal fluid (CSF) antioxidant defences compared to younger individuals [193].”
From The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence (2022) · cites this paper as [193]
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The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence
Varesi, A., Chirumbolo, S., Campagnoli, L. I. M., Pierella, E., Piccini, G. B., Carrara, A., Ricevuti, G., Scassellati, C., Bonvicini, C., & Pascale, A. (2022) · Antioxidants · doi:10.3390/antiox11071224 · Cited by 145 · see citing works
- Authors
- Martin-de-Pablos, A., Córdoba-Fernández, A., & Fernández-Espejo, E.
- Affiliations
- Universidad de Sevilla (ES)
- Venue
- Experimental Gerontology
- Publisher
- Elsevier BV
- Published
- 2018-09
- Volume
- 110
- Pages
- 54-60
- ISSN
- 0531-5565 (ISSN-L)
- OpenAlex
- W2804748556
- Cited by
- 14
- References
- 71
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 2 · 2022: 4 · 2021: 3 · 2020: 1 · 2019: 1 · 2018: 1
- FWCI
- 1.03
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Experimental Gerontology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Junta de Andalucia, Spain (BIO127)
- Sociedad Andaluza de Neurología (SUBAIA2015/006)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Keywords
- midbrain dopaminergic neurons, neuroinflammation, cerebrospinal fluid, aging, brain aging, neurotrophic factors, oxidative stress, antioxidant enzymes, glutathione S-transferase, brain-derived neurotrophic factor, TGF-beta, ferritin, mild cognitive impairment, superoxide dismutase, catalase, glutathione peroxidase
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Aging, Antioxidants, Cross-Sectional Studies, Dopamine, Female, Glutathione Transferase, Humans, Male, Mesencephalon, Middle Aged, Nerve Growth Factors, Oxidative Stress, Brain-Derived Neurotrophic Factor, Young Adult, Cognitive Dysfunction
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