Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 May 23;24(11):9111.
doi: 10.3390/ijms24119111.

Short-Term Irisin Treatment Enhanced Neurotrophin Expression Differently in the Hippocampus and the Prefrontal Cortex of Young Mice

Manuela Dicarlo  1 , Patrizia Pignataro  1   2 , Roberta Zerlotin  1 , Clelia Suriano  1 , Chiara Zecca  3 , Maria Teresa Dell'Abate  3 , Giuseppina Storlino  4 , Angela Oranger  1 , Lorenzo Sanesi  2 , Giorgio Mori  4 , Maria Grano  1 , Graziana Colaianni  1 , Silvia Colucci  2
Affiliations

Short-Term Irisin Treatment Enhanced Neurotrophin Expression Differently in the Hippocampus and the Prefrontal Cortex of Young Mice

Manuela Dicarlo et al. Int J Mol Sci. .

Abstract

As a result of physical exercise, muscle releases multiple exerkines, such as "irisin", which is thought to induce pro-cognitive and antidepressant effects. We recently demonstrated in young healthy mice the mitigation of depressive behaviors induced by consecutive 5 day irisin administration. To understand which molecular mechanisms might be involved in such effect, we here studied, in a group of mice previously submitted to a behavioral test of depression, the gene expression of neurotrophins and cytokines in the hippocampus and prefrontal cortex (PFC), two brain areas frequently investigated in the depression pathogenesis. We found significantly increased mRNA levels of nerve growth factor (NGF) and fibroblast growth factor 2 (FGF-2) in the hippocampus and brain-derived growth factor (BDNF) in the PFC. We did not detect a difference in the mRNA levels of interleukin 6 (IL-6) and IL-1β in both brain regions. Except for BDNF in the PFC, two-way ANOVA analysis did not reveal sex differences in the expression of the tested genes. Overall, our data evidenced a site-specific cerebral modulation of neurotrophins induced by irisin treatment in the hippocampus and the PFC, contributing to the search for new antidepressant treatments targeted at single depressive events with short-term protocols.

Keywords: BDNF; FGF-2; IGF; IL-1β; IL-6; NGF; antidepressant; depression; fibronectin type III domain containing 5; irisin; mice; neuroinflammation; neurotrophins; physical exercise.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The impact of short-term systemic irisin administration on the expression of some neurotrophic/growth factors in the hippocampus. The gene expression of Bdnf (a), Ngf (b), Fgf-2 (c), and Igf-1 (d) was assessed by qRT-PCR in female (n = 7) and male (n = 5) mice for each treatment group. The Shapiro–Wilk test was followed by Student’s t test for all data except for Ngf; * p < 0.05. Data are presented as box-and-whisker plots with median and interquartile ranges, from max to min, with all data points shown.
Figure 2
Figure 2
The effect of short-term systemic irisin administration on the expression of some neurotrophic/growth factors in the PFC. The gene expression of Bdnf (a), Ngf (b), Fgf-2 (c), and Igf-1 (d) was assessed by qRT-PCR in female (n = 7) and male (n = 5) mice for each treatment group. The Shapiro–Wilk test was followed by Student’s t-test for all data; **** p < 0.0001. Data are presented as box-and-whisker plots with median and interquartile ranges, from max to min, with all data points shown.
Figure 3
Figure 3
The effect of short-term systemic irisin treatment on cytokine profile in the hippocampus. The gene expression of Il-6 (a), and Il-1β (b) was evaluated by qRT-PCR in female (n = 7) and male (n = 5) mice for each treatment group. The Shapiro–Wilk test was followed by Student’s t test for Il-6 data analysis and by the Mann–Whitney test for Il-1β. Data are presented as box-and-whisker plots with median and interquartile ranges, from max to min, with all data points shown.
Figure 4
Figure 4
The effect of short-term systemic irisin treatment on cytokine profile in the PFC. The gene expression of Il-6 (a) and Il-1β (b) was evaluated by qRT-PCR in female (n = 7) and male (n = 5) mice for each treatment group. The Shapiro–Wilk test was followed by Student’s t test for Il-6 data analysis and by the Mann–Whitney test for Il-1β. Data are presented as box-and-whisker plots with median and interquartile ranges, from max to min, with all data points shown.
Figure 5
Figure 5
Gene expression of Bdnf (a) and Ngf (b) in the PFC of male and female mice injected with irisin for short-term. The Shapiro–Wilk test was followed by two-way ANOVA analysis and Tukey’s multiple comparison test; * p < 0.05; **** p < 0.0001. Data are presented as box-and-whisker plots with median and interquartile ranges, from max to min, with all data points shown. Black dots indicated vehicle-treated mice; green dots indicated irisin-treated mice.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Ruegsegger G.N., Booth F.W. Health Benefits of Exercise. Cold Spring Harb. Perspect. Med. 2018;8:a029694. doi: 10.1101/cshperspect.a029694. - DOI - PMC - PubMed
    1. Warburton D.E., Nicol C.W., Bredin S.S. Health benefits of physical activity: The evidence. Can. Med. Assoc. J. 2006;174:801–809. doi: 10.1503/cmaj.051351. - DOI - PMC - PubMed
    1. Guan Y., Yan Z. Molecular Mechanisms of Exercise and Healthspan. Cells. 2022;1:872. doi: 10.3390/cells11050872. - DOI - PMC - PubMed
    1. Safdar A., Saleem A., Tarnopolsky M.A. The potential of endurance exercise-derived exosomes to treat metabolic diseases. Nat. Rev. Endocrinol. 2016;12:504–517. doi: 10.1038/nrendo.2016.76. - DOI - PubMed
    1. Zhao R. Irisin at the crossroads of inter-organ communications: Challenge and implications. Front. Endocrinol. 2022;13:989135. doi: 10.3389/fendo.2022.989135. - DOI - PMC - PubMed

Substances