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. 2020 Jun;229(2):e13293.
doi: 10.1111/apha.13293. Epub 2019 Jun 2.

Chronic adult-onset of growth hormone/IGF-I hypersecretion improves cognitive functions and LTP and promotes neuronal differentiation in adult rats

Juan Francisco Martín-Rodríguez  1 , Víctor Darío Ramos-Herrero  1   2 , Gloria G Parras  1   2 , Álvaro Flores-Martínez  1 , Ainara Madrazo-Atutxa  1 , David A Cano  1 , Agnès Gruart  2 , José María Delgado-García  2 , Alfonso Leal-Cerro  1 , Rocío Leal-Campanario  2
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Chronic adult-onset of growth hormone/IGF-I hypersecretion improves cognitive functions and LTP and promotes neuronal differentiation in adult rats

Juan Francisco Martín-Rodríguez et al. Acta Physiol (Oxf). 2020 Jun.

Abstract

Aim: Besides their metabolic and endocrine functions, the growth hormone (GH) and its mediated factor, the insulin-like growth factor I (IGF-I), have been implicated in different brain functions, including neurogenesis. Long-lasting elevated GH and IGF-I levels result in non-reversible somatic, endocrine and metabolic morbidities. However, the subcutaneous implantation of the GH-secreting (GH-S) GC cell line in rats leads to the controllable over-secretion of GH and elevated IGF-I levels, allowing the experimental study of their short-term effects on brain functions.

Methods: Adult rats were implanted with GC cells and checked 10 weeks later, when a GH/IGF-I-secreting tumour was already formed.

Results: Tumour-bearing rats acquired different operant conditioning tasks faster and better than controls and tumour-resected groups. They also presented better retentions of long-term memories in the passive avoidance test. Experimentally evoked long-term potentiation (LTP) in the hippocampus was also larger and longer lasting in the tumour bearing than in the other groups. Chronic adult-onset of GH/IGF-I hypersecretion caused an acceleration of early progenitors, facilitating a faster neural differentiation, maturation and integration in the dentate gyrus, and increased the complexity of dendritic arbours and spine density of granule neurons.

Conclusion: Thus, adult-onset hypersecretion of GH/IGF-I improves neurocognitive functions, long-term memories, experimental LTP and neural differentiation, migration and maturation.

Keywords: LTP; behavioral tests; growth hormone; growth-hormone-secreting tumours; insulin-like growth factor type I; neurogenesis.

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