Portacaval anastomosis disrupts circadian locomotor activity and pineal melatonin rhythms in rats

Zee, Phyllis C.; Mehta, Rajeev; Turek, Fred W.; Blei, Andrés T.

doi:10.1016/0006-8993(91)91209-j

Cited by 56 publications

(46 citation statements)

References 19 publications

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“…Rats after portacaval anastomosis, which represent a model of subclinical encephalopathy, 25 show disruption of circadian rhythms. 5 Thus, it is plausible to hypothesize that sleep disturbance in cirrhosis may be a manifestation of minor forms of encephalopathy. The prevalence of cognitive impairment detected in our patients with a short neuropsychological battery that detects attention and motor deficits 12 is in accordance with previous reports.…”

Section: Discussionmentioning

confidence: 99%

“…5,6,[27][28][29][30] Desynchronization between the social and the internal rhythm mediates the transient insomnia that appears with jet lag or shift work. 31 Likewise, sleep abnormalities may be secondary to malfunctioning circadian timekeeping systems, 32 such as sleep disturbance, that develop with aging.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies from our laboratory have shown that rats subjected to a portacaval anastomosis experience an alteration in the rhythm of circadian locomotor activity as well as the rhythm of pineal melatonin content. 5 In patients with cirrhosis, the diurnal plasma melatonin profile showed a significant delay in the onset of plasma melatonin increase and in its peak nocturnal level. 6 This displacement of the melatonin profile could be a reflection of an alteration in the phase of the circadian clock.…”

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High prevalence of sleep disturbance in cirrhosis

et al. 1998

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Sleep disturbance is a classic sign of hepatic encephalopathy. However, there are limited data regarding its prevalence in cirrhotic patients without overt hepatic encephalopathy. We assessed the characteristics of sleep in cirrhosis using a sleep questionnaire (n ‫؍‬ 44) and actigraphy (n ‫؍‬ 20). The results were compared with those of subjects with chronic renal failure and those of healthy controls. Presence of subclinical hepatic encephalopathy, chronotypology profile, and individual's affective state were also analyzed. The questionnaire indicated an elevated number of cirrhotic patients (47.7%) and patients with chronic renal failure (38.6%) who complained of unsatisfactory sleep compared with healthy controls (4.5%, P F .01). Actigraphy corroborated the deterioration of sleep parameters in cirrhotic patients with unsatisfactory sleep. The sleep disturbance in cirrhosis was not associated with clinical parameters nor with cognitive impairment. Cirrhotic subjects and patients with chronic renal failure with unsatisfactory sleep showed higher scores for depression and anxiety, raising the possibility that the effects of chronic disease may underlie the pathogenesis of sleep disturbance. However, in contrast to chronic renal failure, unsatisfactory sleep in cirrhosis was associated with delayed bedtime, delayed wake-up time, and evening chronotypology. In conclusion, a sleep disturbance is frequent in cirrhotic patients without hepatic encephalopathy and may be related to abnormalities of the circadian timekeeping system. (HEPATOLOGY 1998;27:339-345.)A disturbance of sleep is recognized as one of the early signs of hepatic encephalopathy. 1 However, there are limited data regarding its prevalence in patients with cirrhosis without signs of overt hepatic encephalopathy. Results from a quality of life questionnaire indicated that disturbance in sleep was significantly higher in nonalcoholic cirrhotic patients compared with subjects with another chronic illness, such as Crohn' s disease. 2 In this survey and subsequent data, 3 up to 35% of cirrhotic individuals had difficulties in the area of sleep and rest.The mechanisms responsible for these findings are poorly understood. One possibility is that abnormalities in circadian function may underlie its pathogenesis. The sleep-wake cycle is one of the functions regulated by the circadian clock, the suprachiasmatic nucleus of the anterior hypothalamus, 4 which has efferent connections that influence a large array of biological functions including the secretion of melatonin from the pineal gland. Previous studies from our laboratory have shown that rats subjected to a portacaval anastomosis experience an alteration in the rhythm of circadian locomotor activity as well as the rhythm of pineal melatonin content. 5 In patients with cirrhosis, the diurnal plasma melatonin profile showed a significant delay in the onset of plasma melatonin increase and in its peak nocturnal level. 6 This displacement of the melatonin profile could be a reflection of an alteration in the ...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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High prevalence of sleep disturbance in cirrhosis

et al. 1998

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“…Among these abnormalities are the significantly reduced spontaneous locomotor activity and exploration, 3 as well as the reduced or completely abolished differences between day time and night time activity, suggesting a disruption of their circadian rhythmicity. [4][5][6][7][8][9][10] These rats also have disturbances in their food intake 11 and show marked growth retardation. 12 Although much research has been performed to elucidate the pathophysiological background of PSE, the exact mechanisms that underlie this condition are still largely unclear.…”

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Effects of the histamine H₁receptor blocker, pyrilamine, on spontaneous locomotor activity of rats with long-term portacaval anastomosis

et al. 2000

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To find out whether the changes in the brain histaminergic system are involved in the pathophysiology of portalsystemic encephalopathy, we examined the effects of histamine H 1 receptor blockade on spontaneous locomotor activity, feeding, and circadian rhythmicity in rats with portacaval anastomosis (PCA). Pyrilamine, an H 1 receptor blocker (15 mg/kg/day), was delivered with osmotic minipumps. Spontaneous locomotor activity was recorded for 72 hours in the open-field with an electromagnetic detector. Food intake was monitored twice daily at the end of the light (7 PM) and the dark (7 AM) phases for 3 days. Histamine H 1 receptor density in the suprachiasmatic nucleus (SCN) was examined with receptor autoradiography, employing [ 3 H]pyrilamine. PCA surgery led to decreased movement time and velocity and flattened amplitude of the circadian rhythms of locomotion and feeding. In sham-operated rats, pyrilamine significantly decreased the movement time and velocity, as well as the total food consumption and completely abolished the circadian rhythmicity of locomotion. In contrast, pyrilamine increased the movement time and velocity in PCA-operated rats, particularly in the dark phase, and improved the precision of the circadian rhythms of locomotion and feeding. Histamine H 1 receptor density was not altered by PCA surgery, whereas pyrilamine treatment led to the complete blockade of H 1 receptors in both sham-and PCA-operated rats. We suggest that histaminergic imbalance has contributed to the generation and maintenance of the decreased spontaneous locomotor activity and altered circadian rhythmicity following PCA surgery in the rat, probably via an H 1 receptor-mediated mechanism. (HEPATOL-OGY 2000;31:336-344.)Animal models of human disease provide the means of studying the pathological condition in a way that is not always possible in human patients. The rat with an end-toside portacaval anastomosis (PCA) represents an attractive model of portal-systemic encephalopathy (PSE) 1,2 because many of the behavioral abnormalities that occur in this model correspond to the subclinical forms of PSE. Among these abnormalities are the significantly reduced spontaneous locomotor activity and exploration, 3 as well as the reduced or completely abolished differences between day time and night time activity, suggesting a disruption of their circadian rhythmicity. 4-10 These rats also have disturbances in their food intake 11 and show marked growth retardation. 12 Although much research has been performed to elucidate the pathophysiological background of PSE, the exact mechanisms that underlie this condition are still largely unclear. PSE has been described as a disorder of multiple neurotransmitter systems. 13 Specifically, the histaminergic synaptic imbalance, which becomes apparent shortly 14,15 and persists for at least 8 months after surgery, 12,16-18 is among the most interesting consequences of portacaval shunting in the rat.We have previously shown that rats with PCA have profound disturbances in their brain histaminergi...

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“…Different biological rhythms have been shown to be abnormal in patients with cirrhosis [4][5][6] and in rats with portacaval anastomosis. 7,8 It is unknown whether a common abnormality may also affect the diurnal variation of ALT.…”

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Diurnal variation of serum alanine transaminase activity in chronic liver disease

et al. 1998

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Portacaval anastomosis disrupts circadian locomotor activity and pineal melatonin rhythms in rats

Cited by 56 publications

References 19 publications

High prevalence of sleep disturbance in cirrhosis

High prevalence of sleep disturbance in cirrhosis

Effects of the histamine H₁receptor blocker, pyrilamine, on spontaneous locomotor activity of rats with long-term portacaval anastomosis

Diurnal variation of serum alanine transaminase activity in chronic liver disease

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Portacaval anastomosis disrupts circadian locomotor activity and pineal melatonin rhythms in rats

Cited by 56 publications

References 19 publications

High prevalence of sleep disturbance in cirrhosis

High prevalence of sleep disturbance in cirrhosis

Effects of the histamine H1receptor blocker, pyrilamine, on spontaneous locomotor activity of rats with long-term portacaval anastomosis

Diurnal variation of serum alanine transaminase activity in chronic liver disease

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Effects of the histamine H₁receptor blocker, pyrilamine, on spontaneous locomotor activity of rats with long-term portacaval anastomosis