Chronic treatment with glucocorticoids alters rat hippocampal and prefrontal cortical morphology in parallel with endogenous agmatine and arginine decarboxylase levels
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In the present study, we examined the possible effect of chronic treatment with glucocorticoids on the morphology of the rat brain and levels of endogenous agmatine and arginine decarboxylase (ADC) protein, the enzyme essential for agmatine synthesis. Seven‐day treatment with dexamethasone, at a dose (10 and 50 μg/kg/day) associated to stress effects contributed by glucocorticoids, did not result in obvious morphologic changes in the medial prefrontal cortex and hippocampus, as measured by immunocytochemical staining with β‐tubulin III. However, 21‐day treatment (50 μg/kg/day) produced noticeable structural changes such as the diminution and disarrangement of dendrites and neurons in these areas. Simultaneous treatment with agmatine (50 mg/kg/day) prevented these morphological changes. Further measurement with HPLC showed that endogenous agmatine levels in the prefrontal cortex and hippocampus were significantly increased after 7‐day treatments with dexamethasone in a dose‐dependent manner. On the contrary, 21‐day treatment with glucocorticoids robustly reduced agmatine levels in these regions. The treatment‐caused biphasic alterations of endogenous agmatine levels were also seen in the striatum and hypothalamus. Interestingly, treatment with glucocorticoids resulted in a similar change of ADC protein levels in most brain areas to endogenous agmatine levels: an increase after 7‐day treatment versus a reduction after 21‐day treatment. These results demonstrated that agmatine has neuroprotective effects against structural alterations caused by glucocorticoids in vivo. The parallel alterations in the endogenous agmatine levels and ADC expression in the brain after treatment with glucocorticoids indicate the possible regulatory effect of these stress hormones on the synthesis and metabolism of agmatine in vivo.
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Stress-induced changes in dendritic morphology can be mimicked by chronic administration of high doses of glucocorticoids, which may involve excitotoxicity or oxidative stress.
“Stress-induced changes in dendritic morphology can be mimicked by chronic administration of high doses of glucocorticoids116,117, which may involve excitotoxicity or oxidative stress118.”
From Stress signalling pathways that impair prefrontal cortex structure and function (2009) · cites this paper as [118]
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Sorted by citations
Stress signalling pathways that impair prefrontal cortex structure and function
Arnsten, A. F. T. (2009) · Nature Reviews Neuroscience · doi:10.1038/nrn2648 · Cited by 3,299 · see citing works
Gonçalves, J., Baptista, S., Martins, T., Milhazes, N., Borges, F., Ribeiro, C. F., Malva, J. O., & Silva, A. P. (2010) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2009.07059.x · Cited by 152 · see citing works
- Authors
- Zhu, M., Wang, W., Huang, J., & Regunathan, S.
- Affiliations
- East Tennessee State University (US)
- Soochow University (CN)
- Sun Yat-sen University (CN)
- University of Mississippi Medical Center (US)
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2007-08-03
- Volume
- 103
- Issue
- 5
- Pages
- 1811-1820
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- PMC
- PMC2763426
- OpenAlex
- W2066715131
- Cited by
- 39
- References
- 3
- Citations by year
- 2024: 1 · 2023: 4 · 2020: 1 · 2019: 3 · 2018: 2 · 2017: 2 · 2016: 3 · 2014: 3 · 2013: 4 · 2012: 5
- FWCI
- 1.04
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Digital Commons - East Tennessee State University (East Tennessee State University) (submittedVersion)
- Funders
- National Institutes of Health (5p20rr017701-10)
- National Center for Research Resources (P20-RR-017701, RR 17701)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- glucocorticoids, dexamethasone, agmatine, arginine decarboxylase, hippocampus, prefrontal cortex, neuroprotection, stress hormones, neurotoxicity, striatum, hypothalamus, TUBB3
- MeSH terms
- Agmatine, Analysis of Variance, Animals, Carboxy-Lyases, Drug Administration Schedule, Gene Expression Regulation, Glucocorticoids, Hippocampus, Male, Rats, Sprague-Dawley, Prefrontal Cortex, Rats
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