Selective alteration at the growth-hormone- releasing-hormone nerve terminals during aging in GHRH-green fluorescent protein mice.
Growth hormone (GH) secretion decreases spontaneously during lifespan, and the resulting GH deficiency participates in aging-related morbidity. This deficiency appears to involve a defect in the activity of hypothalamic GH-releasing hormone (GHRH) neurons. Here, we investigated this hypothesis, as well as the underlying mechanisms, in identified GHRH neurons from adult ( approximately 13 weeks old) and aged ( approximately 100 weeks old) transgenic GHRH-green fluorescent protein mice, using morphological, biochemical and electrophysiological methods. Surprisingly, the spontaneous action potential frequency was similar in adult and aged GHRH neurons studied in brain slices. This was explained by a lack of change in the intrinsic excitability, and simultaneous increases in both stimulatory glutamatergic- and inhibitory GABAergic-synaptic currents of aged GHRH neurons. Aging did not decrease GHRH and enhanced green fluorescent protein contents, GHRH neuronal number or GHRH-fibre distribution, but we found a striking enlargement of GHRH-positive axons, suggesting neuropeptide accumulation. Unlike in adults, autophagic vacuoles were evident in aged GHRH-axonal profiles using electron microscopy. Thus, GHRH neurons are involved in aging of the GH axis. Aging had a subtle effect at the nerve terminal level in GHRH neurons, contrasting with the view that neuronal aging is accompanied by more widespread damage.
Alonso
Gérard
G
Département d'Endocrinologie, Institut de Génomique Fonctionnelle, INSERM U661, CNRS UMR 5203, Université Montpellier 1 et 2, Montpellier, France.
Sanchez-Hormigo
Angela
A
Loudes
Catherine
C
El Yandouzi
Taoufik
T
Carmignac
Danielle
D
Faivre-Bauman
Annie
A
Recolin
Bénédicte
B
Epelbaum
Jacques
J
Robinson
Iain C A F
IC
Mollard
Patrice
P
Méry
Pierre-François
PF
D000200:Action Potentials; D000344:Afferent Pathways / Q000502:physiology; D000818:Animals; D016922:Cellular Senescence / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials; D049452:Green Fluorescent Proteins / Q000032:analysis / Q000235:genetics; D013006:Growth Hormone / Q000502:physiology; D013007:Growth Hormone-Releasing Hormone / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000378:metabolism / Q000648:ultrastructure*
C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone