Hypocretin Deficiency in Niemann-Pick Type C with Cataplexy

Kanbayashi, Takashi; M, Abe; Fujimoto, Shigeo; Miyachi, Tomohiro; Takahashi, Tsutomu; Yano, T.; Sawaishi, Yukio; Arii, Junko; Szilágyi, G.; Shimizu, Tatsunori

doi:10.1055/s-2003-38619

Cited by 52 publications

(13 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The decreased density of TH-ir neurons in the LC suggests an intrinsic pathology of this nucleus in NPC. Alternatively, hypocretin (orexin) deficiency, as confirmed in narcoleptic patients with cataplexy, may also occur in some NPC patients [48,49]. Hypothalamic hypocretin promotes the activity of LC neurons, and loss of hypocretin neuronal function can explain the emergence of cataplexy [50,51].…”

Section: Discussionmentioning

confidence: 99%

Brainstem neuropathology in a mouse model of Niemann–Pick disease type C

Zhuo

Saito

Miyata

et al. 2008

Journal of the Neurological Sciences

View full text Add to dashboard Cite

Niemann-Pick disease type C (NPC) is a neurovisceral lipid storage disorder characterized by progressive and widespread neurodegeneration. Although some characteristic symptoms of NPC result from brainstem dysfunction, little information is available about which brainstem structures are affected. In this study, the brainstems of mutant BALB/c NPC1-/- mice with a retroposon insertion in the NPC1 gene were examined for neuropathological changes. In the midbrain, the integrated optic density (IOD) and cell count density of tyrosine-hydroxylase (TH) immunostained neurons were decreased in the substantia nigra. In the pons, TH immunoreactivity in the locus ceruleus (LC) neurons was decreased, while the IOD and the neuronal density of choline acetyltransferase (ChAT)-immunostained neurons in the pedunculopontine tegmental nucleus were preserved. The ChAT immunoreactivity of the hypoglossal nucleus (12N) neurons was not decreased, but Klüver-Barrera staining showed that neuronal density in the nucleus of the solitary tract (NTS) was decreased. Klüver-Barrera and neuronal nuclei (NeuN) staining showed a decrease in neuronal density in the ventral cochlear nucleus, but not in the dorsal cochlear nucleus. Gliosis was widely identified by GFAP staining in various brainstem structures, including the superior and inferior colliculi, the rostral interstitial nucleus of the medial longitudinal fasciculus, the oculomotor complex, the medial geniculate nucleus, the nucleus ambiguus, and the 12N. However, GFAP expression was not augmented in the LC, the cochlear nucleus, or the NTS. These neuropathological findings suggest a basis for the neurological syndromes observed in NPC, such as rigidity, oculomotor symptoms, cataplexy and sleep disturbance, dysphagia, and perceptive deafness.

show abstract

Section: Discussionmentioning

confidence: 99%

Brainstem neuropathology in a mouse model of Niemann–Pick disease type C

Zhuo

Saito

Miyata

et al. 2008

Journal of the Neurological Sciences

View full text Add to dashboard Cite

show abstract

“…This patient did not show cataplexy during her entire clinical course, nor reduced CSF hypocretin-1 level, indicating that the reduced CSF hypocretin-1 level does not correspond to the severity of neurological phenotype. This reduction of CSF hypocretin-1 level might be caused by dysfunction of hypocretin-1 containing cells in Vankova et al (2003), 2) Kanbayashi et al (2003), 3) this case.…”

Section: Discussionmentioning

confidence: 73%

“…The level of CSF hypocretin-1 was determined as moderately low, 174 pg/ml, in the patient. To date, levels of CSF hypocretin-1 have been determined in 7 cases of NPC, including our case (Table 1) (Kanbayashi et al 2003;Vankova et al 2003). Although the 7 samples were assayed at 2 different facilities, an identical assay method, 124 Iodine Hcrt-1 radioimmunoassay, was used for the measurements.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Niemann-Pick Disease Type C: Cataplexy and Hypocretin in Cerebrospinal Fluid

Oyama

Takahashi

Shoji

et al. 2006

Tohoku J. Exp. Med.

View full text Add to dashboard Cite

“…In this study, CSF hypocretin-1 levels were measured in four patients, showing reduced values in two patients, while the other two patients had values in the lower normal range. Hypocretin deficiency in NPC was reported also by other groups [112,120,121]. NPC is among the most frequent medical conditions leading to secondary cataplexy, especially in childhood [122][123][124][125].…”

Section: Niemann-pick Disease Type Cmentioning

confidence: 88%

Narcolepsy

2011

View full text Add to dashboard Cite

Hypocretin Deficiency in Niemann-Pick Type C with Cataplexy

Cited by 52 publications

References 4 publications

Brainstem neuropathology in a mouse model of Niemann–Pick disease type C

Brainstem neuropathology in a mouse model of Niemann–Pick disease type C

Niemann-Pick Disease Type C: Cataplexy and Hypocretin in Cerebrospinal Fluid

Narcolepsy

Contact Info

Product

Resources

About