Melatonin Attenuates Isoflurane‐Induced Acute Memory Impairments in Aged Rats

Abstract

Abstract:Melatonin is an endogenous hormone with neuroprotective effects. Melatonin levels in elderly patients are reduced after surgeries that require anaesthesia. Whether reduced melatonin levels are important for postoperative cognitive dysfunction (POCD) remains unclear. Here, we investigated the effects of melatonin on cognitive dysfunctions induced by isoflurane and mechanisms underlying these effects. Seventy-two 20-month-old Sprague-Dawley rats were randomly divided into six groups (n = 12). These groups included M1 and M10 groups that received intraperitoneal melatonin at 1 mg/kg or 10 mg/kg, respectively, and an ISO group that received 4 hr of inhaled 2% isoflurane. They also included M1+ISO and M10+ISO groups that received 1 mg/kg or 10 mg/kg of melatonin plus 4 hr of inhaled 2% isoflurane, respectively, and a control group that received an equal volume of saline. Injections were administered daily for 14 consecutive days. Memory was assessed in the Morris water maze. Plasma and hippocampi were harvested to determine melatonin concentrations and MT1/MT2 receptor expression. Rats treated only with isoflurane showed significantly longer latencies in Morris water maze test trials compared with the control group, with shorter time in the probe trial (p < 0.05). Although plasma melatonin levels and MT2 expression in the hippocampus were significantly decreased, MT1 expression was higher in the isoflurane group than in the control group (p < 0.001). However, these parameters did not significantly vary in animals administered melatonin compared with controls. Isoflurane may induce cognitive dysfunction by influencing melatonin and MT1/MT2 levels. Melatonin can improve cognitive dysfunction by normalizing plasma melatonin and its receptor levels.

Acute melatonin treatment alters dendritic morphology and circadian clock gene expression in the hippocampus of Siberian Hamsters

“…Although it remains unspecified what function to which diurnal changes in hippocampal neuronal morphology contribute, many studies have reported that dendritic structure of hippocampal neurons is associated with hippocampus‐dependent learning and memory, or cognitive behaviors (Pyter et al, ; Workman et al, ; Crupi et al, ; Walton et al, ); daily variation is observed in some hippocampal functions and hippocampus‐dependent behaviors (Chaudhury et al, ; Ruby et al, ; Tamai et al, ; Takahashi et al, ; Rawashdeh et al, ). Long‐term administration of melatonin modulates hippocampal neuronal plasticity (Rennie et al, ; Ramírez‐Rodríguez et al, , ; Crupi et al, ) and improves cognitive performance (Kilic et al, ; Crupi et al, ; Liu et al, ). In addition to these chronic effects, this study suggests the importance of acute effects of melatonin on daily and seasonal fluctuations in hippocampal physiology.…”

Isoflurane Preconditioning Ameliorates Renal Ischemia-Reperfusion Injury through Antiinflammatory and Antiapoptotic Actions in Rats

“…13,14) In brief, rats were placed in a temperature-controlled, transparent anesthetic chamber with inflow and outflow hoses. Isoflurane (Baxter Healthcare, Deerfield, IL, U.S.A.) was delivered in 100% oxygen at 2 L/min using agent specific vaporizers.…”

Prophylactic Melatonin Attenuates Isoflurane‐Induced Cognitive Impairment in Aged Rats through Hippocampal Melatonin Receptor 2 – cAMP Response Element Binding Signalling

“…The underlying mechanisms for this include neuroinflammation and AD-related neurotoxicity [15,16]. We previously reported that isoflurane exposure affected hippocampal melatonin receptors, which could be stabilized with melatonin pre-treatment [17]. Considering the role of hippocampal MT 2 in AD and related cognitive impairment [10], we hypothesized that MT 2 signalling may also play a role in isoflurane-induced neurotoxicity and cognitive impairment.…”