Hypothalamic neurogenesis persists in the aging brain and is controlled by energy-sensing IGF-I pathway.
Hypothalamic tanycytes are specialized glial cells lining the third ventricle. They are recently identified as adult stem and/or progenitor cells, able to self-renew and give rise to new neurons postnatally. However, the long-term neurogenic potential of tanycytes and the pathways regulating lifelong cell replacement in the adult hypothalamus are largely unexplored. Using inducible nestin-CreER(T2) for conditional mutagenesis, we performed lineage tracing of adult hypothalamic stem and/or progenitor cells (HySC) and demonstrated that new neurons continue to be born throughout adult life. This neurogenesis was targeted to numerous hypothalamic nuclei and produced different types of neurons in the dorsal periventricular regions. Some adult-born neurons integrated the median eminence and arcuate nucleus during aging and produced growth hormone releasing hormone. We showed that adult hypothalamic neurogenesis was tightly controlled by insulin-like growth factors (IGF). Knockout of IGF-1 receptor from hypothalamic stem and/or progenitor cells increased neuronal production and enhanced α-tanycyte self-renewal, preserving this stem cell-like population from age-related attrition. Our data indicate that adult hypothalamus retains the capacity of cell renewal, and thus, a substantial degree of structural plasticity throughout lifespan.
INSERM, Centre de Recherche UMR938, Hôpital Saint-Antoine, Paris, France; Sorbonne Universités, UPMC - Université Pierre et Marie Curie, Paris, France; Faculté de Médecine, Université Paris Descartes, Paris, France.
Zayna
Z
Chaker
INSERM, Centre de Recherche UMR938, Hôpital Saint-Antoine, Paris, France; Sorbonne Universités, UPMC - Université Pierre et Marie Curie, Paris, France.
Caroline
C
George
Sorbonne Universités, UPMC - Université Pierre et Marie Curie, Paris, France.
Marija
M
Petrovska
Faculté de Médecine, Université Paris Descartes, Paris, France.
Jean-Baptiste
JB
Caron
INSERM, Centre de Recherche UMR938, Hôpital Saint-Antoine, Paris, France; Sorbonne Universités, UPMC - Université Pierre et Marie Curie, Paris, France.
Philippe
P
Lacube
Sorbonne Universités, UPMC - Université Pierre et Marie Curie, Paris, France; IBPS, Team Development and Plasticity of Neural Networks, CNRS UMR8246, INSERM U1130, Paris, France.
Isabelle
I
Caillé
INSERM, Centre de Recherche UMR938, Hôpital Saint-Antoine, Paris, France; Sorbonne Universités, UPMC - Université Pierre et Marie Curie, Paris, France. Electronic address: martin.holzenberger@inserm.fr.
Martin
M
Holzenberger
D000375:Aging / Q000473:pathology / Q000502:physiology*; D000818:Animals; D000066670:Cell Plasticity; D000066673:Cell Self Renewal; D063928:Ependymoglial Cells / Q000166:cytology; D007031:Hypothalamus / Q000166:cytology* / Q000254:growth & development*; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D008297:Male; D008822:Mice, Transgenic; D023421:Models, Animal; D055495:Neurogenesis / Q000235:genetics* / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics* / Q000502:physiology*
C519530:insulin-like growth factor-1, mouse; D007334:Insulin-Like Growth Factor I
Adult neurogenesis; Conditional mutagenesis; GHRH; Hypothalamus; IGF-I; Tanycyte