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Therapeutic Effects of Intranasal Administration of Mesenchymal Stem Cell-Derived Secretome in Rats Exposed to Chronic Unpredictable Mild Stress
(MDPI AG, 2025-08-29)
Alba Ávila
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RIVEROS VALLE, MARIA EUGENIA
;
Sofía Adasme
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Coram Guevara
;
Rodrigo Del Rio
Background: Major depression is a significant source of suffering and economic loss. Despite efforts to understand this condition and find better treatments, the burden imposed by this disease continues to rise. Most approved pharmacological treatments for depression focus on controlling the availability of monoamines in synapses. However, accumulating evidence suggests that neuroinflammation, oxidative stress, and reduced hippocampal neurogenesis play key roles as causal factors in the development of major depression symptoms. Therefore, preclinical testing of pharmacological approaches targeting these factors is essential. Mesenchymal stem cells (MSCs) are known for their potential as powerful antioxidants and anti-inflammatory agents, exerting neuroprotective actions in the brain. They produce various therapeutic molecules in a paracrine manner, collectively known as secretome. Methods: In this work, we evaluated the antidepressant potential of repeated intranasal administration of MSC-derived secretome in an animal model of major depressive disorder induced by chronic mild unpredictable stress. Results: We observed that intranasal administration of MSC-derived secretome reduced the appearance of some of the behavioral parameters commonly associated with major depression, including anhedonic, apathetic, and anxious behaviors, inducing a strong reduction in the overall depression score compared to vehicle-treated animals. At the structural level, secretome administration prevented increased astrocyte density and the atrophy of astrocyte processes observed in vehicle-treated stressed animals. Additionally, secretome administration induced an increase in myelin levels and oligodendroglia in the cortex. Conclusions: Our data suggests that intranasal administration of MSC-derived secretome may represent a potential therapeutic alternative to current treatments for this devastating pathology.</jats:p>
1Scopus© Citations 1
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Heart rate and cardiac autonomic responses to concomitant deep breathing, hand grip exercise, and circulatory occlusion in healthy young adult men and women
(2021)
David C. Andrade
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Claudia Melipillan
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Camilo Toledo
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Angélica Rios-Gallardo
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Noah J. Marcus
<jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> <jats:p>Deep breathing (DB) and handgrip (HG) exercise -with and without circulatory occlusion (OC) in muscle-, have been shown to have beneficial effects on cardiovascular function; however, the combination of these maneuvers on heart rate (HR) and cardiac sympathovagal balance have not been previously investigated. Therefore, the aim of the present study was to evaluate the effect of simultaneous DB, HG, and OC maneuvers on the sympathovagal balance in healthy women and men subjects.</jats:p> </jats:sec><jats:sec> <jats:title>Methods and results</jats:title> <jats:p>Electrocardiogram and ventilation were measured in 20 healthy subjects (Women: n = 10; age = 27 ± 4 years; weight = 67.1 ± 8.4 kg; and height = 1.6 ± 0.1 m. Men: n = 10; age = 27 ± 3 years; weight = 77.5 ± 10.1 kg; and height = 1.7 ± 0.1 m) at baseline and during DB, DB + HG, or DB + HG + OC protocols. Heart rate (HR) and respiratory rate were continuously recorded, and spectral analysis of heart rate variability (HRV) were calculated to indirectly estimate cardiac autonomic function. Men and women showed similar HR responses to DB, DB + HG and DB + HG + OC. Men exhibited a significant HR decrease following DB + HG + OC protocol which was accompanied by an improvement in cardiac autonomic control evidenced by spectral changes in HRV towards parasympathetic predominance (HRV High frequency: 83.95 ± 1.45 vs. 81.87 ± 1.50 n.u., DB + HG + OC vs. baseline; p < 0.05). In women, there was a marked decrease in HR after completion of both DB + HG and DB + HG + OC tests which was accompanied by a significant increase in cardiac vagal tone (HRV High frequency: 85.29 ± 1.19 vs. 77.93 ± 0.92 n.u., DB + HG vs. baseline; p < 0.05). No adverse effects or discomfort were reported by men or women during experimental procedures. Independent of sex, combination of DB, HG, and OC was tolerable and resulted in decreases in resting HR and elevations in cardiac parasympathetic tone.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusions</jats:title> <jats:p>These data indicate that combined DB, HG and OC are effective in altering cardiac sympathovagal balance and reducing resting HR in healthy men and women.</jats:p> </jats:sec>
6Scopus© Citations 3
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Activation of Intra-nodose Ganglion P2X7 Receptors Elicit Increases in Neuronal Activity
(2023)
Julio Alcayaga
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Jorge Vera
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Mauricio Reyna-Jeldes
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Alejandra A. Covarrubias
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Claudio Coddou
Scopus© Citations 2 2
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Cardiac remodeling and arrhythmogenesis are ameliorated by administration of Cx43 mimetic peptide Gap27 in heart failure rats
(2020)
Claudia M. Lucero
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David C. Andrade
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Camilo Toledo
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Hugo S. Díaz
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Katherin V. Pereyra
<jats:title>Abstract</jats:title><jats:p>Alterations in connexins and specifically in 43 isoform (Cx43) in the heart have been associated with a high incidence of arrhythmogenesis and sudden death in several cardiac diseases. We propose to determine salutary effect of Cx43 mimetic peptide Gap27 in the progression of heart failure. High-output heart failure was induced by volume overload using the arterio-venous fistula model (AV-Shunt) in adult male rats. Four weeks after AV-Shunt surgery, the Cx43 mimetic peptide Gap27 or scrambled peptide, were administered via osmotic minipumps (AV-Shunt<jats:sub>Gap27</jats:sub> or AV-Shunt<jats:sub>Scr</jats:sub>) for 4 weeks. Cardiac volumes, arrhythmias, function and remodeling were determined at 8 weeks after AV-Shunt surgeries. At 8<jats:sup>th</jats:sup> week, AV-Shunt<jats:sub>Gap27</jats:sub> showed a marked decrease in the progression of cardiac deterioration and showed a significant improvement in cardiac functions measured by intraventricular pressure-volume loops. Furthermore, AV-Shunt<jats:sub>Gap27</jats:sub> showed less cardiac arrhythmogenesis and cardiac hypertrophy index compared to AV-Shunt<jats:sub>Scr</jats:sub>. Gap27 treatment results in no change Cx43 expression in the heart of AV-Shunt rats. Our results strongly suggest that Cx43 play a pivotal role in the progression of cardiac dysfunction and arrhythmogenesis in high-output heart failure; furthermore, support the use of Cx43 mimetic peptide Gap27 as an effective therapeutic tool to reduce the progression of cardiac dysfunction in high-output heart failure.</jats:p>
Scopus© Citations 30 1
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Topical Application of Connexin43 Hemichannel Blocker Reduces Carotid Body-Mediated Chemoreflex Drive in Rats
(2018)
David C. Andrade
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Rodrigo Iturriaga
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Camilo Toledo
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Claudia M. Lucero
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Hugo S. Díaz
Scopus© Citations 2 3
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Contribution of peripheral and central chemoreceptors to sympatho-excitation in heart failure
(2016)
Camilo Toledo
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David C. Andrade
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Claudia Lucero
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Harold D. Schultz
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Noah Marcus
2Scopus© Citations 47
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Reply from Noah J. Marcus, Rodrigo Del Rio and Harold D. Schultz
(2014)
Noah J. Marcus
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Rodrigo Del Rio
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Harold D. Schultz
1Scopus© Citations 1
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Relevance of the Carotid Body Chemoreflex in the Progression of Heart Failure
(2015)
David C. Andrade
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Claudia Lucero
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Camilo Toledo
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Carlos Madrid
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Noah J. Marcus
<jats:p>Chronic heart failure (CHF) is a global health problem affecting millions of people. Autonomic dysfunction and disordered breathing patterns are commonly observed in patients with CHF, and both are strongly related to poor prognosis and high mortality risk. Tonic activation of carotid body (CB) chemoreceptors contributes to sympathoexcitation and disordered breathing patterns in experimental models of CHF. Recent studies show that ablation of the CB chemoreceptors improves autonomic function and breathing control in CHF and improves survival. These exciting findings indicate that alterations in CB function are critical to the progression of CHF. Therefore, better understanding of the physiology of the CB chemoreflex in CHF could lead to improvements in current treatments and clinical management of patients with CHF characterized by high chemosensitivity. Accordingly, the main focus of this brief review is to summarize current knowledge of CB chemoreflex function in different experimental models of CHF and to comment on their potential translation to treatment of human CHF.</jats:p>
29Scopus© Citations 23
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Carbon monoxide: A new player in the redox regulation of connexin hemichannels
(2015)
RETAMAL LUCERO, MAURICIO ANTONIO
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Carmen G. León-Paravic
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EZQUER, EDUARDO MARCELO
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Rodrigo Del Rio
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EZQUER, EDUARDO FERNANDO
Scopus© Citations 15 4
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Extracellular Cysteine in Connexins: Role as Redox Sensors
(2016)
RETAMAL LUCERO, MAURICIO ANTONIO
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Isaac E. García
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Bernardo I. Pinto
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Amaury Pupo
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David Báez
Scopus© Citations 30 1

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