Open AccessSelective alteration at the growth‐hormone‐ releasing‐hormone nerve terminals during aging in GHRH‐green fluorescent protein mice
Author(s) -
Alonso Gérard,
SanchezHormigo Angela,
Loudes Catherine,
El Yandouzi Taoufik,
Carmignac Danielle,
FaivreBauman Annie,
Recolin Bénédicte,
Epelbaum Jacques,
Robinson Iain CAF,
Mollard Patrice,
Méry PierreFrançois
Publication year - 2007
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/j.1474-9726.2007.00276.x
Subject(s) - biology , medicine , endocrinology , growth hormone–releasing hormone , gabaergic , hormone , neuropeptide , immunocytochemistry , glutamatergic , neuroscience , inhibitory postsynaptic potential , glutamate receptor , receptor , growth hormone , biochemistry
Summary 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 (∼13 weeks old) and aged (∼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.