Abstract
ObjectivesBilateral destruction of the olfactory bulbs is known to cause behavioral changes analogous to symptoms of depression. Curcumin, a traditional Indian spice is currently being investigated in different psychiatric problems including depression. Dietary phytochemicals are currently used as an adjuvant therapy to accelerate their therapeutic efficacy. Therefore, the present study is an attempt to elucidate the neuroprotective mechanism of curcumin and its co-administration with piperine against olfactory bulbectomy induced depression in rats.MethodsRats undergone olfactory bulbs ablations were analyzed after post-surgical rehabilitation period of 2 weeks. Animals were then treated with different doses of curcumin (100, 200 and 400 mg/kg; p.o.), piperine (20 mg/kg; p.o.) and their combination daily for another 2 weeks. Imipramine (10 mg/kg; i.p.) served as a standard control. Various behavioral tests like forced swim test (FST), open field behaviour and sucrose preference test (SPT) were performed, followed by estimation of biochemical, mitochondrial, molecular and histopathological parameters in rat brain.ResultsAblation of olfactory bulbs caused depression-like symptoms as evidenced by increased immobility time in FST, hyperactivity in open field arena, and anhedonic like response in SPT along with alterations in mitochondrial enzyme complexes, increased serum corticosterone levels and oxidative damage. These deficits were integrated with increased inflammatory cytokines (TNF-α) and apoptotic factor (caspase-3) levels along with a marked reduction in neurogenesis factor (BDNF) in the brain of olfactory bulbectomized (OBX) rats. Curcumin treatment significantly and dose-dependently restored all these behavioral, biochemical, mitochondrial, molecular and histopathological alterations associated with OBX induced depression. Further, co-administration of piperine with curcumin significantly potentiated their neuroprotective effects as compared to their effects alone.ConclusionsThe present study highlights that curcumin along with piperine exhibits neuroprotection against olfactory bulbectomy induced depression possibly by modulating oxidative-nitrosative stress induced neuroinflammation and apoptosis.
Highlights
Depression is one of the severe psychiatric disorders and has been estimated as the second biggest contributor of the global load of neurological diseases and disability for the year 2020 [1]
Ablation of olfactory bulbs caused depression-like symptoms as evidenced by increased immobility time in forced swim test (FST), hyperactivity in open field arena, and anhedonic like response in sucrose preference test (SPT) along with alterations in mitochondrial enzyme complexes, increased serum corticosterone levels and oxidative damage. These deficits were integrated with increased inflammatory cytokines (TNF-a) and apoptotic factor levels along with a marked reduction in neurogenesis factor (BDNF) in the brain of olfactory bulbectomized (OBX) rats
Co-administration of piperine with curcumin significantly potentiated their neuroprotective effects as compared to their effects alone
Summary
Depression is one of the severe psychiatric disorders and has been estimated as the second biggest contributor of the global load of neurological diseases and disability for the year 2020 [1]. It is characterized by low mood, loss of interest in daily activities and marked reduction in pleasure activities. Olfactory bulbectomy (OBX) has been widely used as an experimental model of depression [2]. Bilateral destruction of the olfactory bulbs caused complex alterations in behavioral, biochemical and cellular cascades, many of which are comparable to those seen in patients with major depression [2].
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