Impaired hypothalamic endocrine function in neuroacanthocytosis

Kontoleon, P; Ilias, Ιoannis; Matsouka, A.; Gatzonis, Stylianos; Spiropoulou, C.; Papapetrou, Peter D.

doi:10.1016/s0967-5868(03)00166-8

Cited by 2 publications

(1 citation statement)

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“…For example, severe atrophy, neuronal loss, and gliosis have been found in the hippocampus, temporal, and frontal lobes, or prefrontal cortex, of some patients [ 5 , 29 , 30 ]. Other authors report cerebellar atrophy [ 31 , 32 ], impairment of the hypothalamic endocrine function [ 33 ], and oculomotor abnormalities due to brainstem dysfunction [ 34 ]. Thus, the high-to-moderate VPS13A expression levels in these brain areas evidences the important role of this protein in neuronal functioning and survival throughout the nervous system.…”

Section: Discussionmentioning

confidence: 99%

Unraveling the Spatiotemporal Distribution of VPS13A in the Mouse Brain

García-García

Chaparro-Cabanillas

Coll-Manzano

et al. 2021

IJMS

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Loss-of-function mutations in the human vacuolar protein sorting the 13 homolog A (VPS13A) gene cause Chorea-acanthocytosis (ChAc), with selective degeneration of the striatum as the main neuropathologic feature. Very little is known about the VPS13A expression in the brain. The main objective of this work was to assess, for the first time, the spatiotemporal distribution of VPS13A in the mouse brain. We found VPS13A expression present in neurons already in the embryonic stage, with stable levels until adulthood. VPS13A mRNA and protein distributions were similar in the adult mouse brain. We found a widespread VPS13A distribution, with the strongest expression profiles in the pons, hippocampus, and cerebellum. Interestingly, expression was weak in the basal ganglia. VPS13A staining was positive in glutamatergic, GABAergic, and cholinergic neurons, but rarely in glial cells. At the cellular level, VPS13A was mainly located in the soma and neurites, co-localizing with both the endoplasmic reticulum and mitochondria. However, it was not enriched in dendritic spines or the synaptosomal fraction of cortical neurons. In vivo pharmacological modulation of the glutamatergic, dopaminergic or cholinergic systems did not modulate VPS13A concentration in the hippocampus, cerebral cortex, or striatum. These results indicate that VPS13A has remarkable stability in neuronal cells. Understanding the distinct expression pattern of VPS13A can provide relevant information to unravel pathophysiological hallmarks of ChAc.

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