TY - JOUR
T1 - Age-dependent change of RFRP-3 neuron numbers and innervation in female mice
AU - Angelopoulou, Eleni
AU - Kalsbeek, Andries
AU - Simonneaux, Valérie
N1 - Funding Information: This work was supported by the European Commission through the Neurotime Erasmus Mundus program and by the Centre National de la Recherche Française. Funding Information: This work was supported by the European Commission through the Neurotime Erasmus Mundus program and by the Centre National de la Recherche Fran?aise. Publisher Copyright: © 2021
PY - 2022/4/1
Y1 - 2022/4/1
N2 - In female mammals, reproductive senescence is a complex process involving progressive ovarian dysfunction, associated with altered central control of the hypothalamic-pituitary-gonadal axis and desynchronization of the circadian system. The objective of this study was to investigate age-dependent changes in the daily regulation of Arg-Phe amide-related peptide-3 (RFRP-3), a hypothalamic peptide involved in reproduction, in female C57BL/6 J mice of different age groups (4, 13, and 19 months old) sampled at their diestrus stage. We found an age-dependent decrease in the total number of RFRP-3 neurons and in the relative number of activated (i.e. c-Fos-positive) RFRP-3 neurons. RFRP-3 neuronal activation exhibited a daily variation in young and middle-aged mice, which was abolished in 19-month-old mice. We also found a daily variation in the number of RFRP-3 neurons receiving close vasopressin (AVP)- and vasoactive intestinal peptide (VIP)-ergic fiber appositions in mice aged 4 and 13 months, but not in 19-month-old mice. However, we found no daily or age-dependent changes in the AVP and VIP fiber density in the dorsomedial hypothalamus. Plasma LH levels were similar in mice aged 4 and 13 months, but were markedly increased in 19-month-old mice. The present findings indicate that the number of RFRP-3 positive neurons is downregulated during old age and that the daily changes in their innervation by the circadian peptides AVP and VIP are abolished. This age-associated reduced (rhythmic) activity of the inhibitory RFRP-3 system could be implicated in the elevated LH secretion observed during reproductive senescence.
AB - In female mammals, reproductive senescence is a complex process involving progressive ovarian dysfunction, associated with altered central control of the hypothalamic-pituitary-gonadal axis and desynchronization of the circadian system. The objective of this study was to investigate age-dependent changes in the daily regulation of Arg-Phe amide-related peptide-3 (RFRP-3), a hypothalamic peptide involved in reproduction, in female C57BL/6 J mice of different age groups (4, 13, and 19 months old) sampled at their diestrus stage. We found an age-dependent decrease in the total number of RFRP-3 neurons and in the relative number of activated (i.e. c-Fos-positive) RFRP-3 neurons. RFRP-3 neuronal activation exhibited a daily variation in young and middle-aged mice, which was abolished in 19-month-old mice. We also found a daily variation in the number of RFRP-3 neurons receiving close vasopressin (AVP)- and vasoactive intestinal peptide (VIP)-ergic fiber appositions in mice aged 4 and 13 months, but not in 19-month-old mice. However, we found no daily or age-dependent changes in the AVP and VIP fiber density in the dorsomedial hypothalamus. Plasma LH levels were similar in mice aged 4 and 13 months, but were markedly increased in 19-month-old mice. The present findings indicate that the number of RFRP-3 positive neurons is downregulated during old age and that the daily changes in their innervation by the circadian peptides AVP and VIP are abolished. This age-associated reduced (rhythmic) activity of the inhibitory RFRP-3 system could be implicated in the elevated LH secretion observed during reproductive senescence.
KW - RFRP-3
KW - Reproductive senescence, aging hypothalamus
KW - Vasoactive intestinal peptide
KW - Vasopressin
UR - http://www.scopus.com/inward/record.url?scp=85122236864&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.npep.2021.102224
DO - https://doi.org/10.1016/j.npep.2021.102224
M3 - Article
C2 - 34998113
SN - 0143-4179
VL - 92
JO - Neuropeptides
JF - Neuropeptides
M1 - 102224
ER -