Dose-Related Effects of Chronic Antidepressants on Neuroprotective Proteins BDNF, Bcl-2 and Cu/Zn-SOD in Rat Hippocampus
Abstract
It has been proposed that antidepressants have neuroprotective effects on hippocampal neurons. To further test this hypothesis, brain-derived neurotrophic factor (BDNF), B cell lymphoma protein-2 (Bcl-2), and copper-zinc superoxide dismutase (Cu/Zn-SOD) were examined immunohistochemically in hippocampal neurons of Sprague-Dawley rats following daily treatment with 5 or 10 mg/kg of amitriptyline or venlafaxine for 21 days. At 5 mg/kg, both amitriptyline and venlafaxine increased the intensity of BDNF immunostaining in hippocampal pyramidal neurons, and the intensity of Bcl-2 immunostaining in hippocampal mossy fibers, but did not alter the Cu/Zn-SOD immunoreactivity. The high dose of venlafaxine, however, decreased the intensity of BDNF immunostaining in all subareas of the hippocampus and increased the intensity of Cu/Zn-SOD immunostaining in the dentate granular cell layer. The high dose of amitriptyline increased the intensity of Cu/Zn-SOD immunostaining, but did not affect the immunoreactivity of Bcl-2 or BDNF. These findings suggest that the chronic administration of amitriptyline or venlafaxine at 5 mg/kg, but not 10 mg/kg, may be neuroprotective to hippocampal neurons. These dose-related effects of antidepressant drugs on hippocampal neurons may have relevance to disparate findings in the field.
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Low dose (5 mg/kg) of amitriptyline and venlafaxine increases BDNF immunostaining in hippocampal pyramidal neurons and Bcl-2 immunostaining in hippocampal mossy fibers, but does not alter Cu/Zn-SOD immunoreactivity.
“low dose (5 mg/kg) of amitriptyline and venlafaxine increased the intensity of BDNF immunostaining in hippocampal pyramidal neurons and the intensity of Bcl-2 immunostaining in hippocampal mossy fibers, but did not alter the Cu/Zn-SOD immunoreactivity.”
From Preclinical and Clinical Evidence of Antioxidant Effects of Antidepressant Agents: Implications for the Pathophysiology of Major Depressive Disorder (2012) · cites this paper as [21]
High dose (10 mg/kg) of venlafaxine decreases BDNF immunostaining in all subareas of the hippocampus and increases Cu/Zn-SOD immunostaining in the dentate granular cell layer.
“High dose (10 mg/kg) of venlafaxine, however, decreased the intensity of BDNF immunostaining in all subareas of the hippocampus and increased the intensity of Cu/Zn-SOD immunostaining in the dentate granular cell layer [21].”
From Preclinical and Clinical Evidence of Antioxidant Effects of Antidepressant Agents: Implications for the Pathophysiology of Major Depressive Disorder (2012) · cites this paper as [21]
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- Authors
- Xu, H., Steven Richardson, J., & Li, X.-M.
- Affiliations
- University of Saskatchewan (CA)
- ORCID
- Xu, Haiyun
- Venue
- Neuropsychopharmacology
- Published
- 2003-01
- Volume
- 28
- Issue
- 1
- Pages
- 53-62
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- OpenAlex
- W2070554778
- Cited by
- 167
- References
- 60
- Citations by year
- 2026: 2 · 2024: 2 · 2023: 3 · 2022: 5 · 2021: 5 · 2020: 1 · 2019: 2 · 2018: 5 · 2017: 7 · 2016: 9 · 2015: 10 · 2014: 8 · 2013: 7 · 2012: 10
- FWCI
- 7.93
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Psychiatric Research Foundation
- Canadian Institutes of Health Research
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- antidepressants, neuroprotection, hippocampal neurons, amitriptyline, venlafaxine, brain-derived neurotrophic factor, Bcl-2, copper-zinc superoxide dismutase, dose-dependent effects, chronic drug administration, mossy fibers, dentate gyrus
- MeSH terms
- Venlafaxine Hydrochloride, Amitriptyline, Animals, Antidepressive Agents, Antidepressive Agents, Tricyclic, Cyclohexanols, Densitometry, Dose-Response Relationship, Drug, Hippocampus, Immunohistochemistry, Male, Superoxide Dismutase, Weight Gain, Rats, Sprague-Dawley, Selective Serotonin Reuptake Inhibitors, Neuroprotective Agents, Brain-Derived Neurotrophic Factor, Proto-Oncogene Proteins c-bcl-2, Rats
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