Dietary fish oil inhibits mechanical allodynia and thermal hyperalgesia in diabetic rats by blocking nuclear factor-κB-mediated inflammatory pathways.

One of the most common complications of early-onset diabetes mellitus is peripheral diabetic neuropathy, which is manifested either by loss of nociception or by allodynia and hyperalgesia. Diabetes mellitus is a common metabolic disease in human beings with characteristic symptoms of hyperglycemia, chronic inflammation and insulin resistance. Dietary fatty acids, especially polyunsaturated fatty acids, have been shown anti-inflammatory role in various experimental conditions. The present study investigated the effects of fish oil supplementation on the inflammation in the dorsal root ganglion (DRG) of streptozotocin (STZ)-induced diabetes rats. The effects of diabetes and fish oil treatment on the allodynia and hyperalgesia were also evaluated. Dietary fish oil effectively attenuated both allodynia and hyperalgesia induce by STZ injection. Along with the behavioral findings, DRG from fish oil-treated diabetic rats displayed a decrease in inflammatory cytokines and the expression of nuclear factor-κB (NF-κB) compared with untreated diabetic rats. Fish oil supplementation also increased the phosphorylation of AKT in DRG of diabetic rats. These results suggested that dietary fish oil-inhibited allodynia and hyperalgesia in diabetic rats may stem from its anti-inflammatory potential by regulating NF-κB and AKT. Fish oil might be useful as an adjuvant therapy for the prevention and treatment of diabetic complications.

Salidroside prevents cognitive impairment induced by chronic cerebral hypoperfusion in rats.

OBJECTIVE: To investigate the effects of salidroside on cognitive dysfunction induced by chronic cerebral hypoperfusion in rats. METHODS: Male Sprague-Dawley rats (n = 36) were divided into three groups (n = 12 per group): sham operation; bilateral permanent occlusion of the common carotid arteries (2-VO); 2-VO + salidroside. Rats received 20 mg/kg per day salidroside or vehicle intraperitoneal injection beginning the day before surgery and continuing until 34 days postoperatively. Cognitive function was evaluated by Morris water maze test and hippocampal long-term potentiation (LTP) measurement. Hippocampal neuronal apoptosis was evaluated via immunofluorescence. RESULTS: Chronic cerebral hypoperfusion caused marked cognitive deficit and LTP inhibition. These effects were largely ameliorated by salidroside administration. Salidroside prevented caspase-3 activation, increased the ratio of Bax/Bcl-2, and reversed hippocampal neuronal loss induced by chronic cerebral hypoperfusion. CONCLUSIONS: Salidroside prevents cognitive deficits caused by chronic cerebral hypoperfusion in rats, and alleviates apoptosis in the hippocampal CA1 area.

Fish oil modulates glycogen synthase kinase-3 signaling pathway in diabetes-induced hippocampal neurons apoptosis.

Previous research has demonstrated that diabetes induces learning and memory deficits. However, the mechanism of memory impairment induced by diabetes is poorly understood. Dietary fatty acids, especially polyunsaturated fatty acids, have been shown to enhance learning and memory and prevent memory deficits in various experimental conditions. The present study investigated the effects of fish oil supplementation on the neuron apoptosis in the hippocampus of streptozotocin (STZ)-induced diabetes rats, further explored the effect of fish oil on the phosphorylation of protein kinase B and glycogen synthase kinase-3 beta. The effects of diabetes and fish oil treatment on the spatial learning and memory were also evaluated using the Morris Water Maze. STZ-induced diabetes impaired spatial learning and memory of rats, which was associated with the apoptosis of hippocampal neurons and oxidative stress. Fish oil administration ameliorated cognitive deficit, reduced oxidative stress, increased AKT phosphorylation, decreased GSK-3ß phosphorylation, and decreased pro-apoptotic molecules expression, which protected the hippocampal neurons from apoptosis in diabetic rats. These results suggested a potential role for fish oil as an adjuvant therapy for the prevention and treatment of diabetic complications.

A high ratio of dietary n-3/n-6 polyunsaturated fatty acids improves obesity-linked inflammation and insulin resistance through suppressing activation of TLR4 in SD rats.

Dietary ratios of n-3/n-6 polyunsaturated fatty acids (PUFAs) have been implicated in controlling markers of metabolic disorders, including obesity, insulin resistance (IR), inflammation, and lipid profiles, which are also presumed to be partly related to type 2 diabetes mellitus (T2DM). However, molecular mechanisms of the different PUFAs related to metabolic disorders have not been systematically addressed. The present study aimed to investigate the impact of dietary n-3/n-6 PUFA ratios on obesity and IR and, further, to determine the underlying mechanisms. For 16 weeks, 32 SD male rats, randomly divided into four groups (n = 8 per group), received one of the following diets: normal chow, high saturated fatty acid (SFA), high n-3/n-6 PUFA ratio (1∶1, PUFA¹:¹), or low n-3/n-6 PUFA ratio (1∶4, PUFA¹:4). Following the experimental diet period, metabolic parameters related to obesity and IR were measured. Compared to SFA diet-fed rats, PUFA¹:¹ diet-fed rats exhibited decreased body and visceral fat weight, lowered blood lipids, and improved glucose tolerance and insulin sensitivity. Interestingly, these changes were accompanied with decreased expression levels of circulating pro-inflammatory cytokines, including tumor necrosis factor α, interleukin-6, and C-reactive protein. Moreover, the TLR4 protein and mRNA levels were markedly down-regulated by PUFA¹:¹ compared with SFA; however, PUFA¹:4 diet-fed rats failed to exhibit these changes. Cumulatively, our data highlight a role for a PUFA¹:¹ diet in the prevention of obesity and related metabolic disorders by suppressing the activation of TLR4, a critical modulator of pro-inflammatory cytokines.

Ionic mechanisms of the effects of sleep deprivation on excitability in hippocampal pyramidal neurons.

It has been confirmed that sleep has a key role in learning and memory. Our previous study indicated that paradoxical sleep deprivation (PSD) impairs spatial learning ability of rats, and the decrease in membrane excitability of CA1 pyramidal neurons contributes to deficits in performing a spatial learning task. To investigate the further ionic mechanisms, the persistent sodium currents (I(NaP)), the hyperpolarization-activated cation current (I(h)), and their roles in neuron excitability were detected. PSD decreased I(NaP) and suppressed spike ADP, which leads to the reduction of neuron excitability and to the increase of firing accommodation. In addition, PSD reduced the I(h) amplitude and the rebound excitability of CA1 pyramidal neurons. The results of the present study suggested that I(h) and I(NaP) contributed to the inhibitory effect of PSD on neuron excitability, further influencing learning and memory processing. Modulating the ion channels and increasing the membrane excitability of hippocampal neurons are possible targets for preventing the effects of paradoxical sleep deprivation.