A deficit of brain dystrophin 71 impairs hypothalamic osmostat.
Patients with Duchenne muscular dystrophy (DMD) and mdx mice, devoid of dystrophin proteins, show altered ionic homeostasis. To clarify dystrophin's involvement in the central control of osmotic stimuli, we investigated the effect of the disruption of Dp71, the major form of dystrophin in the brain, on the hypothalamoneurohypophysis system (HNHS) osmoregulatory response. Dp71 and Dp140 are the principal DMD gene products in the supraoptic nucleus (SON) and neurohypophysis (NH). They are present in astrocyte and pituicyte end-feet, suggesting involvement in both intrinsic osmosensitivity of the SON and vasopressin (AVP) release from the NH. In Dp71-null mice, the cellular distribution of Dp140 was modified, this protein being detected on the membrane of magnocellular soma. The plasma osmolality of Dp71-null mice was lower than that of wild-type mice under normal conditions, and this difference was maintained after salt loading, indicating a change in the set point for osmoregulation in the absence of Dp71. The increase in AVP levels detected in the SON and NH of the wild-type was not observed in Dp71-null mice following salt loading, and the increase in AVP mRNA levels in the SON was smaller in Dp71-null than in wild-type mice. This suggests that Dp71 may be involved in the functional activity of the HNHS. Its astrocyte end-feet localization emphasizes the importance of neuronal-vascular-glial interactions for the central detection of osmolality. In the SON, Dp71 may be involved in osmosensitivity and definition of the "osmostat," whereas, in the neurohypophysis, it may be involved in fine-tuning AVP release.
Benabdesselam
Roza
R
Unité de Recherches, Faculté des Sciences Biologiques/UMMTO, BP 17, Tizi-Ouzou, Algérie.
Sene
Abdoulaye
A
Raison
Danièle
D
Benmessaoud-Mesbah
Ouahiba
O
Ayad
Ghazi
G
Mornet
Dominique
D
Yaffe
David
D
Rendon
Alvaro
A
Hardin-Pouzet
Hélène
H
Dorbani-Mamine
Latifa
L
D000818:Animals; D001769:Blood / Q000378:metabolism; D001921:Brain / Q000502:physiology*; D016189:Dystrophin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D007031:Hypothalamus / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010904:Pituitary Gland, Posterior / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D012492:Salts / Q000378:metabolism; D013495:Supraoptic Nucleus / Q000502:physiology; D014667:Vasopressins / Q000378:metabolism; D014867:Water / Q000378:metabolism; D014882:Water-Electrolyte Balance / Q000502:physiology*
C094406:140-kDa dystrophin; D016189:Dystrophin; D012333:RNA, Messenger; D012492:Salts; C085339:apo-dystrophin 1; D014867:Water; D014667:Vasopressins