Ontogenetic Changes in the Expression of the Lin28 Protein in the Rat Hypothalamic Tuberal Nuclei

The hypothalamus is a primary regulator of homeostasis, biological rhythms and adaptation to different environment factors. It also participates in the aging regulation. The expression of neurons containing Lin28 was studied by immunohistochemistry in male rats aged 2, 6, 12, and 24 months in the tuberal region of the rat hypothalamus. We have shown for the first time the presence of Lin28-immunoreactive (IR) neurons in the ventromedial nucleus (VMH) and their absence in the dorsomedial and arcuate nuclei in all studied animals. With aging, the percentage of Lin28-IR neurons increases from 37 +/- 4.7 in 2-month-old rat until 76 +/- 4.6 in 6-month-old and further decreases to 41 +/- 7.3 in 12-month-old rat and 28 +/- 5.5 in 24-month-old rats. Many VMH Lin28-IR neurons colocalized components of insulin signaling including mTOR, Raptor, PI3K and Akt. The percentage of Lin28/Akt-IR neurons was maximal in 6-month-old and 1-year-old rats compared to 2-month-old and 2-year-old animals. The proportion of Lin28/PI3K-IR neurons significantly increased from 77 +/- 1.2 in 2-month-old rat until 99 +/- 0.3 in 24-month-old rats and 96-99% of Lin28-IR neurons colocalized mTOR and mTORC1 component Raptor without statistically significant differences in all studied age groups. Thus, Lin28 expresses only in the VMH neurons of the tuberal nuclei of the hypothalamus and the Lin 28 expression changes during the development together with the components of PI3K-Akt-mTOR signaling.

Automated summary

The hypothalamus plays a crucial role in regulating homeostasis, biological rhythms, adaptation, and aging. This study found the presence of Lin28-immunoreactive neurons in the ventromedial nucleus of the hypothalamus and their absence in other studied nuclei. The percentage of Lin28-positive neurons increases with age, peaks at 6 months and 1 year, and then declines. These neurons also colocalize components of insulin signaling, indicating their involvement in metabolic regulation. The findings suggest that Lin28 expression in the hypothalamus changes with development and signaling components.