Olfactory bulbectomy in mice triggers transient and long-lasting behavioral impairments and biochemical hippocampal disturbances
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Updated: Mar 7, 2026
Olfactory Assays for Mouse Models of Neurodegenerative Disease
Published on: August 25, 2014
Roberto Farina de Almeida1, Marcelo Ganzella2, Daniele Guilhermano Machado1
1Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Abstract:
Major depressive disorder (MDD) is a neuropsychiatric disease that is associated with profound disturbances in affected individuals. Elucidating the pathophysiology of MDD has been frustratingly slow, especially concerning the neurochemical events and brain regions associated with disease progression. Thus, we evaluated the time-course (up to 8weeks) behavioral and biochemical effects in mice that underwent to a bilateral olfactory bulbectomy (OBX), which is used to modeling depressive-like behavior in rodents. Similar to the symptoms in patients with MDD, OBX induced long-lasting (e.g., impairment of habituation to novelty, hyperactivity and an anxiety-like phenotype) and transient (e.g., loss of self-care and motivational behavior) behavioral effects. Moreover, OBX temporarily impaired hippocampal synaptosomal mitochondria, in a manner that would be associated with hippocampal-related synaptotoxicity. Finally, long-lasting pro-oxidative (i.e., increased levels of reactive oxygen species and nitric oxide and decreased glutathione levels) and pro-inflammatory (i.e., increased levels of pro-inflammatory cytokines IL-1, IL-6, TNF-α and decreased anti-inflammatory cytokine IL-10 levels) effects were induced in the hippocampus by OBX. Additionally, these parameters were transiently affected in the posterior and frontal cortices. This study is the first to suggest that the transient and long-lasting behavioral effects from OBX strongly correlate with mitochondrial, oxidative and inflammatory parameters in the hippocampus; furthermore, these effects show a weak correlation with these parameters in the cortex. Our findings highlight the underlying mechanisms involved in the biochemical time course of events related to depressive behavior.
Insights
Olfactory bulbectomy (OBX) in mice models major depressive disorder (MDD) by inducing long-lasting behavioral changes. These effects correlate with hippocampal mitochondrial dysfunction, oxidative stress, and inflammation, offering insights into MDD pathophysiology.
Area of Science:
- Neuroscience
- Biochemistry
- Pathophysiology
Background:
- Major depressive disorder (MDD) pathophysiology remains poorly understood, particularly concerning neurochemical events and brain regions involved in disease progression.
- Rodent models are crucial for investigating MDD mechanisms, with olfactory bulbectomy (OBX) serving as a common model for depressive-like behavior.
Purpose of the Study:
- To investigate the time-course of behavioral and biochemical effects following OBX in mice.
- To elucidate the correlation between OBX-induced behavioral changes and alterations in mitochondrial, oxidative, and inflammatory parameters in the hippocampus and cortex.
Main Methods:
- Bilateral olfactory bulbectomy (OBX) was performed on mice to induce depressive-like behavior.
- Behavioral assessments included habituation to novelty, hyperactivity, anxiety-like phenotype, self-care, and motivational behavior over 8 weeks.
- Biochemical analyses focused on hippocampal and cortical synaptosomal mitochondria, oxidative stress markers (ROS, NO, glutathione), and inflammatory cytokines (IL-1, IL-6, TNF-α, IL-10).
Main Results:
- OBX induced long-lasting behavioral impairments (e.g., impaired habituation, hyperactivity, anxiety) and transient effects (e.g., loss of self-care, motivational deficits).
- Hippocampal synaptosomal mitochondria were temporarily impaired post-OBX, suggesting synaptotoxicity.
- Long-lasting oxidative stress and inflammation were observed in the hippocampus, while these effects were transient in the posterior and frontal cortices.
Conclusions:
- OBX-induced behavioral effects in mice show a strong correlation with hippocampal mitochondrial, oxidative, and inflammatory changes.
- These findings highlight the hippocampus as a key region in the pathophysiology of OBX-modeled MDD.
- The study provides insights into the biochemical mechanisms underlying the time course of depressive behavior.
