Cited by 167Treatment of Major DepressionNerve injury and regenerationNeuroscience and Neuropharmacology Research

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Dose-Related Effects of Chronic Antidepressants on Neuroprotective Proteins BDNF, Bcl-2 and Cu/Zn-SOD in Rat Hippocampus

Xu, Haiyun, Steven Richardson, J, Li, Xin-Min·2003·Neuropsychopharmacology

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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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Authors: Xu, H., Steven Richardson, J., & Li, X.-M.
Affiliations: University of Saskatchewan (CA)
ORCID: Xu, Haiyun
Venue: Neuropsychopharmacology
Publisher: Springer Science and Business Media LLC
Published: 2003-01
Volume: 28
Issue: 1
Pages: 53-62
ISSN: 0893-133X (ISSN-L)
1740-634X
DOI: 10.1038/sj.npp.1300009
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 (medical) › 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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Dose-Related Effects of Chronic Antidepressants on Neuroprotective Proteins BDNF, Bcl-2 and Cu/Zn-SOD in Rat Hippocampus

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