Background: Depression and Alzheimer's disease (AD) are co-morbid conditions. Neuropsychiatric symptoms have been reported as prodromal symptoms of AD-like dementia and soluble forms of beta amyloid peptide (Aβ), the main constituent of insoluble plaques typical of AD brains, have been implicated in such an effect. We have previously shown that intracerebral injection of Aβ can evoke a depressive-like state in rats, accompanied by neurochemical and neuroendocrine alterations reminiscent of depressive symptoms in humans. AD and depression are crucially linked by neuroinflammation and cyclooxygenase II (COX-2) enzyme involvement is an intriguing field of research. Indeed, its pharmacological inhibition has shown both antidepressant and Aβ modulating effects. Methods: Male rats were exposed to sub-chronic celecoxib (15 mg/kg/day sc for 8 days), a selective COX-2 inhibitor or vehicle (saline), starting from the day before central intracerebroventricular injection of Aβ peptide (5µL of 4 µM solution or vehicle for sham). Animals were tested for depressive-like behaviour by using the forced swimming test paradigm and prefrontal serotonin (5-HT) content and plasma Aβ levels were further evaluated. Results: We found that celecoxib treatment prevented the pro-depressive effects induced by Aβ. Moreover, it also prevented the reduction in 5-HT content in prefrontal cortex of Aβ-treated rats and decreased their plasma Aβ levels. Conclusions: Taken together, our data indicate that celecoxib could be a suitable pharmaceutical tool for the treatment of depressive state related to increased Aβ levels.

Sub-chronic celecoxib prevents soluble beta amyloid-induced depressive-like behaviour in rats

Morgese, M. G.
Writing – Original Draft Preparation
;
SCHIAVONE, STEFANIA
Data Curation
;
Bove, M.
Methodology
;
Mhillaj, E.
Methodology
;
Tucci, P.
Methodology
;
Trabace, L.
Writing – Original Draft Preparation
2018

Abstract

Background: Depression and Alzheimer's disease (AD) are co-morbid conditions. Neuropsychiatric symptoms have been reported as prodromal symptoms of AD-like dementia and soluble forms of beta amyloid peptide (Aβ), the main constituent of insoluble plaques typical of AD brains, have been implicated in such an effect. We have previously shown that intracerebral injection of Aβ can evoke a depressive-like state in rats, accompanied by neurochemical and neuroendocrine alterations reminiscent of depressive symptoms in humans. AD and depression are crucially linked by neuroinflammation and cyclooxygenase II (COX-2) enzyme involvement is an intriguing field of research. Indeed, its pharmacological inhibition has shown both antidepressant and Aβ modulating effects. Methods: Male rats were exposed to sub-chronic celecoxib (15 mg/kg/day sc for 8 days), a selective COX-2 inhibitor or vehicle (saline), starting from the day before central intracerebroventricular injection of Aβ peptide (5µL of 4 µM solution or vehicle for sham). Animals were tested for depressive-like behaviour by using the forced swimming test paradigm and prefrontal serotonin (5-HT) content and plasma Aβ levels were further evaluated. Results: We found that celecoxib treatment prevented the pro-depressive effects induced by Aβ. Moreover, it also prevented the reduction in 5-HT content in prefrontal cortex of Aβ-treated rats and decreased their plasma Aβ levels. Conclusions: Taken together, our data indicate that celecoxib could be a suitable pharmaceutical tool for the treatment of depressive state related to increased Aβ levels.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11369/372047
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