Evaluation for CSF histamine levels in many disorders and measurements of hypothalamic neuropeptides in the patients with Kleine-Levin syndrome

(1)我们首次报道了组胺在原发性中枢神经系统过度睡眠中的减少，如发作性睡病和特发性过度睡眠(Kanbayashi，2009)。然而，其他疾病中的组胺水平仍然未知。我们进一步估计了几种神经系统疾病的脑脊液中的组胺。组胺能神经元仅位于下丘脑后部的结节乳头核(TMN)，并将轴突投射到大脑的不同区域。组胺在大脑中的释放不仅来自TMN组胺神经元，也来自于脉络丛中丰富的脑肥大细胞，以及外周血液转移到中枢神经系统(CNS)。这些细胞释放的组胺可能会影响脑脊液的组胺水平。据报道，脑膜炎和脑炎的脑脊液组胺水平升高(Ito 2010)。在脱髓鞘疾病中，MS的组胺水平低，ADEM的组胺水平高。此外，我们发现与MSA相比，PSP和CBD的脑脊液组胺水平降低(Kanbayashi2012)。这些疾病组胺水平的差异可能是由下丘脑后部功能障碍引起的。(2)Kleine-Levin综合征(KLS)是一种以反复发作的过量睡眠和进食为特征的神经系统疾病。我们假设这种疾病是由下丘脑神经肽的损伤引起的。因此，我们检测了下丘脑多肽和神经递质，如α，MSH，AgRP，Mch，Nesfatin-1，Oresin和组胺。在神经肽和神经递质水平上没有具体的发现(Kanbayashi2010)。虽然我们发现神经性厌食症患者的脑脊液AgRP水平升高，但KLS患者的组胺水平相对较低(Ito 2010)。

(1) We first reported that histamine decreases in the primary CNS hypersomnia, such as narcolepsy and idiopathic hypersomnia (Kanbayashi 2009). However, the histamine levels in other diseases are still unknown. We have further estimated the histamine in CSF of several neurological diseases. Histaminergic neurons are located exclusively in the tuberomammillary nucleus (TMN) of the posterior hypothalamus and project their axons to various brain regions. Histamine is released in the brain not only from TMN histamine neurons, but also from brain mast cell enriched in the choroid plexus, and peripheral blood transferred to central nervous system (CNS). Histamine release by these cells may contribute to CSF histamine levels. Increased CSF histamine levels have been reported in meningitis and encephalitis (Ito 2010). In the demyelinating diseases, histamine levels of MS were low but those of ADEM were high. In addition, we found reductions in CSF histamine levels in PSP and CBD compared to MSA (Kanbayashi2012). The differences of histamine levels in these disorders may be caused by the dysfunctions of posterior hypothalamus. (2) Kleine-Levin Syndrome (KLS) is a neurological disorder characterized by recurring periods of excessive amounts of sleeping and eating. We hypothesized that this disorder is caused by the damage to hypothalamic neuropeptides. The refore, we measured hypothalamic peptides and neurotransmitters, such as, αMSH, AgRP, MCH, nesfatin-1, orexin and histamine. There were no specific findings in the levels of neuropeptides and neurotransmitters (Kanbayashi2010). While we found that CSF AgRP were elevated in the patients with anorexia nervosa, the histamine levels are relatively low among the patiets with KLS (Ito2010).