Abstract
BackgroundPost-traumatic stress disorder (PTSD) is an important psychological disease that can develop following the physical experience or witnessing of traumatic events. The psychopathological response to traumatic stressors increases inflammation in the hippocampus and induces memory deficits. Melatonin (MTG) plays critical roles in circadian rhythm disorders, Alzheimer’s disease, and other neurological disorders. However, the cognitive efficiency of MTG and its mechanisms of action in the treatment of PTSD remain unclear. Thus, the present study investigated the effects of MTG on spatial cognitive impairments stimulated by single prolonged stress (SPS) in rats, an animal model of PTSD. Male rats received intraperitoneal (i.p.) administration of various doses of MTG for 21 consecutive days after the SPS procedure.ResultsSPS-stimulated cognitive impairments in the object recognition task and Morris water maze were reversed by MTG treatment (25 mg/kg, i.p). Additionally, MTG significantly increased cognitive memory-related decreases in cAMP-response element-binding (CREB) protein and mRNA levels in the hippocampus. Our results also demonstrate that MTG significantly inhibited SPS-stimulated cognitive memory impairments by inhibiting the expression of proinflammatory cytokines, including tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in the rat brain.ConclusionThe present results indicate that MTG can be beneficial for SPS-stimulated memory impairments via changes in CREB expression and proinflammatory mediators. Thus, MTG may be a prophylactic strategy for the prevention or mitigation of the progression of some features of the PTSD pathology.
Highlights
Post-traumatic stress disorder (PTSD) is an important psychological disease that can develop following the physical experience or witnessing of traumatic events
Suppression of the increase in plasma CORT level by Effects of MTG on single prolonged stress (SPS)‐stimulated memory impairment The novel object recognition for learning and memory function was indicated by means of the exploration times of familiar and novel objects and by computation of the discrimination indix by the object recognition test (ORT) (Fig. 3a and b)
The present results demonstrated that SPS-stimulated memory impairments were associated with serious impairment in performance on tests of learning and memory function as well as corresponding signs of neurodegeneration in the brain, including decreased brain-derived neurotrophic factor (BDNF) and cAMP-response element-binding (CREB) expression and increased proinflammatory cytokine levels in the hippocampus
Summary
Post-traumatic stress disorder (PTSD) is an important psychological disease that can develop following the physical experience or witnessing of traumatic events. The present study investigated the effects of MTG on spatial cognitive impairments stimulated by single prolonged stress (SPS) in rats, an animal model of PTSD. Declarative memory dysfunction is related to post-traumatic stress disorder (PTSD), which manifests following exposure to severe trauma [1]. PTSD patients exhibit significant cognitive deficits, including damaged declarative and working memory abilities and impairments in attention and concentration [6,7,8]. The cognitive deficits observed in PTSD patients have been hypothesized to be the result of unpleasant flashback memories that temporarily interfere with the capability to procedure new memories or information [9,10,11]. Placing a rat in a context in which it has been shocked impairs memory on an entirely different test [7, 11], such as the localization of a hidden platform in a water maze
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