Pro-neurogenic effect of fluoxetine in the olfactory bulb is concomitant to improvements in social memory and depressive-like behavior of socially isolated mice

Abstract

Although loneliness is a human experience, it can be estimated in laboratory animals deprived from physical contact with conspecifics. Rodents under social isolation (SI) tend to develop emotional distress and cognitive impairment. However, it is still to be determined whether those conditions present a common neural mechanism. Here, we conducted a series of behavioral, morphological, and neurochemical analyses in adult mice that underwent to 1 week of SI. We observed that SI mice display a depressive-like state that can be prevented by enriched environment, and the antidepressants fluoxetine (FLX) and desipramine (DES). Interestingly, chronic administration of FLX, but not DES, was able to counteract the deleterious effect of SI on social memory. We also analyzed cell proliferation, neurogenesis, and astrogenesis after the treatment with antidepressants. Our results showed that the olfactory bulb (OB) was the neurogenic niche with the highest increase in neurogenesis after the treatment with FLX. Considering that after FLX treatment social memory was rescued and depressive-like behavior decreased, we propose neurogenesis in the OB as a possible mechanism to unify the FLX ability to counteract the deleterious effect of SI.

SARS-CoV-2 infection results in lasting and systemic perturbations post recovery

“…The olfactory bulbs are functionally connected to—and can thus influence activity of—the limbic system, which controls appetitive, sensory, emotional, and cognitive responses. Indeed, prior preclinical studies link olfactory bulb damage with depressive phenotypes that can be reversed with antidepressant treatment (Guarnieri et al, 2020; Hellweg et al, 2007; Kelly et al, 1997; Song and Leonard, 2005). These data suggest that chronic nasal and olfactory bulb inflammation may drive neurodegeneration and structural changes consistent with long COVID symptoms (Hasegawa-Ishii et al, 2017; 2019).…”

Cognitive Consequences of Social Isolation During COVID-19: side effects and treatments

“…Oral Fluoxetine consumption has improved the depletion of serotonin in the hippocampus; and, anxiety, depression, and social deficits have reversed during social isolation. Moreover, brain neurogenesis has improved, which plays a crucial role in emotional deficit development (62)(63)(64). With Fluoxetine treatment, as an anti-depressant, metabolic impairment were also reversed (65).…”

“…With Fluoxetine treatment, as an anti-depressant, metabolic impairment were also reversed (65). Some documents have claimed that Fluoxetine that is attached to mitochondria can change anion channels voltage, and finally, alleviate depression (64,66).…”

“…It can also perform as effective as fluoxetine; however, side effects associated with a pharmacological drug would not happen with EE treatment. Isolation-induced decrease in 5-HT level has been regulated through EE treatment, and the 5-HT level has increased in the hippocampus and prefrontal cortex (64). Finally, some investigations revealed that using an EE increases the rate of neurogenesis to maintain proliferation of dentate gyrus (DG) hippocampal cells in socially isolated mice, which results in maintaining social recognition memory and improving amnesic-like impairment (101).…”

Long-Term Impact of Social Isolation and Molecular Underpinnings

“…Prolonged social isolation also affects different aspects of physiology. It can impair neurogenesis in the olfactory bulb (OB), the ventral hippocampus (VH) , and the dentate gyrus (DG), and lead to reduced volume of some of these structures and the prefrontal cortex (Lu et al, 2003;Day-Wilson et al, 2006;Guarnieri et al, 2020). The loss of medial prefrontal cortex volume, but not its total number of neurons, resembles that observed in individuals with schizophrenia (Day-Wilson et al, 2006).…”