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Histamine Transmission Modulates the Phenotype of Murine Narcolepsy Caused by Orexin Neuron Deficiency.

Bastianini S, Silvani A, Berteotti C, Lo Martire V, Cohen G, Ohtsu H, Lin JS, Zoccoli G - PLoS ONE (2015)

Bottom Line: Thus, these narcolepsy signs are neither caused nor abrogated by the absence of histamine.Conversely, the lack of histamine produced obesity in HDC-KO and to a greater extent also in DM.Defects of histamine transmission may thus modulate the metabolic and respiratory phenotype of murine narcolepsy.

View Article: PubMed Central - PubMed

Affiliation: PRISM Laboratory, Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy.

ABSTRACT
Narcolepsy type 1 is associated with loss of orexin neurons, sleep-wake derangements, cataplexy, and a wide spectrum of alterations in other physiological functions, including energy balance, cardiovascular, and respiratory control. It is unclear which narcolepsy signs are directly related to the lack of orexin neurons or are instead modulated by dysfunction of other neurotransmitter systems physiologically controlled by orexin neurons, such as the histamine system. To address this question, we tested whether some of narcolepsy signs would be detected in mice lacking histamine signaling (HDC-KO). Moreover, we studied double-mutant mice lacking both histamine signaling and orexin neurons (DM) to evaluate whether the absence of histamine signaling would modulate narcolepsy symptoms produced by orexin deficiency. Mice were instrumented with electrodes for recording the electroencephalogram and electromyogram and a telemetric arterial pressure transducer. Sleep attacks fragmenting wakefulness, cataplexy, excess rapid-eye-movement sleep (R) during the activity period, and enhanced increase of arterial pressure during R, which are hallmarks of narcolepsy in mice, did not occur in HDC-KO, whereas they were observed in DM mice. Thus, these narcolepsy signs are neither caused nor abrogated by the absence of histamine. Conversely, the lack of histamine produced obesity in HDC-KO and to a greater extent also in DM. Moreover, the regularity of breath duration during R was significantly increased in either HDC-KO or DM relative to that in congenic wild-type mice. Defects of histamine transmission may thus modulate the metabolic and respiratory phenotype of murine narcolepsy.

No MeSH data available.


Related in: MedlinePlus

Sleep-related changes in arterial pressure.(A) and (B), values of mean arterial pressure (MAP) during wakefulness (W), non-rapid-eye-movement sleep (N), and rapid-eye-movement sleep (R) in the light and dark periods, respectively. In this and the other panels, data are means ± SEM in HDC-KO (n = 11), DM (n = 7), and WT (n = 11). (C) and (D), time course of MAP changes during transitions between N and R shown in absolute values and in percentage of the values at baseline, respectively. Horizontal bars refer to the first and the last 20 s of the transitions. E, representative tracing of MAP, electroencephalogram (EEG) and electromyogram (EMG) during a transition from N to R in a DM mouse, highlighting a dramatic and sustained arterial pressure (AP) increase in R. The arrow in E indicates the awakening from R. The grey vertical bars in C, D, and E indicate the transition point between states. *, †, and ‡, P < 0.05, WT vs. DM, WT vs. HDC-KO, and HDC-KO vs. DM, respectively (t-tests).
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pone.0140520.g004: Sleep-related changes in arterial pressure.(A) and (B), values of mean arterial pressure (MAP) during wakefulness (W), non-rapid-eye-movement sleep (N), and rapid-eye-movement sleep (R) in the light and dark periods, respectively. In this and the other panels, data are means ± SEM in HDC-KO (n = 11), DM (n = 7), and WT (n = 11). (C) and (D), time course of MAP changes during transitions between N and R shown in absolute values and in percentage of the values at baseline, respectively. Horizontal bars refer to the first and the last 20 s of the transitions. E, representative tracing of MAP, electroencephalogram (EEG) and electromyogram (EMG) during a transition from N to R in a DM mouse, highlighting a dramatic and sustained arterial pressure (AP) increase in R. The arrow in E indicates the awakening from R. The grey vertical bars in C, D, and E indicate the transition point between states. *, †, and ‡, P < 0.05, WT vs. DM, WT vs. HDC-KO, and HDC-KO vs. DM, respectively (t-tests).

Mentions: DM had higher arterial pressure during R than either HDC-KO or WT in the light and dark periods (Fig 4A and 4B). Analysis of transitions from N to R revealed that arterial pressure was also higher in DM than in either HDC-KO or WT during the last part of the N episodes before the transitions to R (Fig 4C), and increased more in DM than in either HDC-KO or WT on passing from N to R (Fig 4D). No significant differences occurred between HDC-KO and WT.


Histamine Transmission Modulates the Phenotype of Murine Narcolepsy Caused by Orexin Neuron Deficiency.

Bastianini S, Silvani A, Berteotti C, Lo Martire V, Cohen G, Ohtsu H, Lin JS, Zoccoli G - PLoS ONE (2015)

Sleep-related changes in arterial pressure.(A) and (B), values of mean arterial pressure (MAP) during wakefulness (W), non-rapid-eye-movement sleep (N), and rapid-eye-movement sleep (R) in the light and dark periods, respectively. In this and the other panels, data are means ± SEM in HDC-KO (n = 11), DM (n = 7), and WT (n = 11). (C) and (D), time course of MAP changes during transitions between N and R shown in absolute values and in percentage of the values at baseline, respectively. Horizontal bars refer to the first and the last 20 s of the transitions. E, representative tracing of MAP, electroencephalogram (EEG) and electromyogram (EMG) during a transition from N to R in a DM mouse, highlighting a dramatic and sustained arterial pressure (AP) increase in R. The arrow in E indicates the awakening from R. The grey vertical bars in C, D, and E indicate the transition point between states. *, †, and ‡, P < 0.05, WT vs. DM, WT vs. HDC-KO, and HDC-KO vs. DM, respectively (t-tests).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4608736&req=5

pone.0140520.g004: Sleep-related changes in arterial pressure.(A) and (B), values of mean arterial pressure (MAP) during wakefulness (W), non-rapid-eye-movement sleep (N), and rapid-eye-movement sleep (R) in the light and dark periods, respectively. In this and the other panels, data are means ± SEM in HDC-KO (n = 11), DM (n = 7), and WT (n = 11). (C) and (D), time course of MAP changes during transitions between N and R shown in absolute values and in percentage of the values at baseline, respectively. Horizontal bars refer to the first and the last 20 s of the transitions. E, representative tracing of MAP, electroencephalogram (EEG) and electromyogram (EMG) during a transition from N to R in a DM mouse, highlighting a dramatic and sustained arterial pressure (AP) increase in R. The arrow in E indicates the awakening from R. The grey vertical bars in C, D, and E indicate the transition point between states. *, †, and ‡, P < 0.05, WT vs. DM, WT vs. HDC-KO, and HDC-KO vs. DM, respectively (t-tests).
Mentions: DM had higher arterial pressure during R than either HDC-KO or WT in the light and dark periods (Fig 4A and 4B). Analysis of transitions from N to R revealed that arterial pressure was also higher in DM than in either HDC-KO or WT during the last part of the N episodes before the transitions to R (Fig 4C), and increased more in DM than in either HDC-KO or WT on passing from N to R (Fig 4D). No significant differences occurred between HDC-KO and WT.

Bottom Line: Thus, these narcolepsy signs are neither caused nor abrogated by the absence of histamine.Conversely, the lack of histamine produced obesity in HDC-KO and to a greater extent also in DM.Defects of histamine transmission may thus modulate the metabolic and respiratory phenotype of murine narcolepsy.

View Article: PubMed Central - PubMed

Affiliation: PRISM Laboratory, Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy.

ABSTRACT
Narcolepsy type 1 is associated with loss of orexin neurons, sleep-wake derangements, cataplexy, and a wide spectrum of alterations in other physiological functions, including energy balance, cardiovascular, and respiratory control. It is unclear which narcolepsy signs are directly related to the lack of orexin neurons or are instead modulated by dysfunction of other neurotransmitter systems physiologically controlled by orexin neurons, such as the histamine system. To address this question, we tested whether some of narcolepsy signs would be detected in mice lacking histamine signaling (HDC-KO). Moreover, we studied double-mutant mice lacking both histamine signaling and orexin neurons (DM) to evaluate whether the absence of histamine signaling would modulate narcolepsy symptoms produced by orexin deficiency. Mice were instrumented with electrodes for recording the electroencephalogram and electromyogram and a telemetric arterial pressure transducer. Sleep attacks fragmenting wakefulness, cataplexy, excess rapid-eye-movement sleep (R) during the activity period, and enhanced increase of arterial pressure during R, which are hallmarks of narcolepsy in mice, did not occur in HDC-KO, whereas they were observed in DM mice. Thus, these narcolepsy signs are neither caused nor abrogated by the absence of histamine. Conversely, the lack of histamine produced obesity in HDC-KO and to a greater extent also in DM. Moreover, the regularity of breath duration during R was significantly increased in either HDC-KO or DM relative to that in congenic wild-type mice. Defects of histamine transmission may thus modulate the metabolic and respiratory phenotype of murine narcolepsy.

No MeSH data available.


Related in: MedlinePlus