Olfactory bulbectomy induces nociceptive alterations associated with gliosis in male rats

Major depressive disorder (MDD) is a major health concern worldwide with a wide array of symptoms. Emerging evidence suggests a high comorbidity between MDD and chronic pain, however, the relationship between these two diseases is not completely understood. Growing evidence suggests that glial cells...

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Published inIBRO neuroscience reports Vol. 14; pp. 494 - 506
Main Authors Galindo-Paredes, Gumaro, Flores, Gonzalo, Morales-Medina, Julio César
Format Journal Article
LanguageEnglish
Published Netherlands Elsevier Ltd 01.06.2023
Elsevier
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Summary:Major depressive disorder (MDD) is a major health concern worldwide with a wide array of symptoms. Emerging evidence suggests a high comorbidity between MDD and chronic pain, however, the relationship between these two diseases is not completely understood. Growing evidence suggests that glial cells play a key role in both disorders. Hence, we examined the effect of olfactory bulbectomy (OBX), a well-known model of depression-related behavior, on nociceptive behaviors and the number and morphology of astrocytes and glial cells in brain regions involved in the control of nociceptive processes in male rats. The brain regions analyzed included the basolateral amygdala (BLA), central amygdala (CeA), prefrontal cortex (PFC), and CA1 subregion of the hippocampus. A battery of behavioral tests, mechanical allodynia, thermal cold allodynia and mechanical hyperalgesia, was evaluated before and four weeks after OBX. Quantitative morphological analysis, as well as assessment of the number of glial fibrillary acidic protein (GFAP) and ionizing calcium-binding adaptor molecule 1 (Iba1) positive astrocytes and microglia were carried out to characterize glial remodeling and density, respectively. OBX caused mechanical and cold allodynia in an asynchronous pattern. The cold allodynia was noticeable one week following surgery, while mechanical allodynia became apparent two weeks after surgery. In the BLA, CeA and CA1, OBX caused significant changes in glial cells, such as hypertrophy and hypotrophy in GFAP-positive astrocytes and Iba1-positive microglia, respectively. Iba1-positive microglia in the PFC underwent selective hypotrophy due to OBX and OBX enhanced both GFAP-positive astrocytes and Iba1-positive microglia in the BLA. In addition, OBX increased the number of GFAP-positive astrocytes in the CeA and CA1. The amount of Iba1-positive microglia in the PFC also increased as a result of OBX. Furthermore, we found that there was a strong link between the observed behaviors and glial activation in OBX rats. Overall, our work supports the neuroinflammatory hypothesis of MDD and the comorbidity between pain and depression by demonstrating nociceptive impairment and significant microglial and astrocytic activation in the brain. •The olfactory bulbectomy (OBX) is a model of depression-related behavior.•OBX induces mechanical and cold allodynia in both paws that appear asynchronously.•OBX results in hypertrophy and increased numbers of GFAP-positive astrocytes in various brain regions.•OBX results in hypotrophy in Iba1-positive glial cells in various brain regions.•The behavioral deficits and the glial dysfunction is correlated in OBX rats.
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ISSN:2667-2421
2667-2421
DOI:10.1016/j.ibneur.2023.05.006