Hippocampal Mitophagy Contributes to Spatial Memory Via Maintaining Neurogenesis During the Development of Mice

Overview

Journal CNS Neurosci Ther

Specialties Neurology
Pharmacology

Date 2024 Jun 18

PMID 38887162

Authors

Le Xu

Saboor Saeed

Xinxu Ma

Xufeng Cen

Yifei Sun

Yanan Tian

Xuhong Zhang

Danhua Zhang

Anying Tang

Hetong Zhou

Jianbo Lai

Hongguang Xia

Shaohua Hu

Affiliations

Soon will be listed here.

Abstract

Background: Impaired mitochondrial dynamics have been identified as a significant contributing factor to reduced neurogenesis under pathological conditions. However, the relationship among mitochondrial dynamics, neurogenesis, and spatial memory during normal development remains unclear. This study aims to elucidate the role of mitophagy in spatial memory mediated by neurogenesis during development.

Methods: Adolescent and adult male mice were used to assess spatial memory performance. Immunofluorescence staining was employed to evaluate levels of neurogenesis, and mitochondrial dynamics were assessed through western blotting and transmission electron microscopy. Pharmacological interventions further validated the causal relationship among mitophagy, neurogenesis, and behavioral performance during development.

Results: The study revealed differences in spatial memory between adolescent and adult mice. Diminished neurogenesis, accompanied by reduced mitophagy, was observed in the hippocampus of adult mice compared to adolescent subjects. Pharmacological induction of mitophagy in adult mice with UMI-77 resulted in enhanced neurogenesis and prolonged spatial memory retention. Conversely, inhibition of mitophagy with Mdivi-1 in adolescent mice led to reduced hippocampal neurogenesis and impaired spatial memory.

Conclusion: The observed decline in spatial memory in adult mice is associated with decreased mitophagy, which affects neurogenesis in the dentate gyrus. This underscores the therapeutic potential of enhancing mitophagy to counteract age- or disease-related cognitive decline.

Citing Articles

Retinoic Acid Promotes Neuronal Differentiation While Increasing Proteins and Organelles Related to Autophagy.

Lazzeri G, Lenzi P, Signorini G, Raffaelli S, Giammattei E, Natale G Int J Mol Sci. 2025; 26(4).

PMID: 40004155 PMC: 11855701. DOI: 10.3390/ijms26041691.

Hippocampal mitophagy contributes to spatial memory via maintaining neurogenesis during the development of mice.

Xu L, Saeed S, Ma X, Cen X, Sun Y, Tian Y CNS Neurosci Ther. 2024; 30(6):e14800.

PMID: 38887162 PMC: 11183181. DOI: 10.1111/cns.14800.

References

Ramsaran A, Wang Y, Golbabaei A, Aleshin S, de Snoo M, Yeung B . A shift in the mechanisms controlling hippocampal engram formation during brain maturation. Science. 2023; 380(6644):543-551. DOI: 10.1126/science.ade6530. View

Mitra K . Mitochondrial fission-fusion as an emerging key regulator of cell proliferation and differentiation. Bioessays. 2013; 35(11):955-64. DOI: 10.1002/bies.201300011. View

Spear L . The adolescent brain and age-related behavioral manifestations. Neurosci Biobehav Rev. 2000; 24(4):417-63. DOI: 10.1016/s0149-7634(00)00014-2. View

Kameda S, Fukushiro D, Trombin T, Procopio-Souza R, Patti C, Hollais A . Adolescent mice are more vulnerable than adults to single injection-induced behavioral sensitization to amphetamine. Pharmacol Biochem Behav. 2011; 98(2):320-4. DOI: 10.1016/j.pbb.2011.01.013. View

Frankland P, Kohler S, Josselyn S . Hippocampal neurogenesis and forgetting. Trends Neurosci. 2013; 36(9):497-503. DOI: 10.1016/j.tins.2013.05.002. View

Lin W, Wilbrecht L . Making sense of strengths and weaknesses observed in adolescent laboratory rodents. Curr Opin Psychol. 2022; 45:101297. DOI: 10.1016/j.copsyc.2021.12.009. View

Johnson C, Wilbrecht L . Juvenile mice show greater flexibility in multiple choice reversal learning than adults. Dev Cogn Neurosci. 2011; 1(4):540-51. PMC: 3177141. DOI: 10.1016/j.dcn.2011.05.008. View

Pantiya P, Thonusin C, Chunchai T, Pintana H, Ongnok B, Nawara W . Long-term lifestyle intervention is superior to transient modification for neuroprotection in D-galactose-induced aging rats. Life Sci. 2023; 334:122248. DOI: 10.1016/j.lfs.2023.122248. View

Frankland P, Bontempi B . The organization of recent and remote memories. Nat Rev Neurosci. 2005; 6(2):119-30. DOI: 10.1038/nrn1607. View

10.

Maryanovich M, Zaltsman Y, Ruggiero A, Goldman A, Shachnai L, Zaidman S . An MTCH2 pathway repressing mitochondria metabolism regulates haematopoietic stem cell fate. Nat Commun. 2015; 6:7901. DOI: 10.1038/ncomms8901. View

11.

Marxreiter F, Regensburger M, Winkler J . Adult neurogenesis in Parkinson's disease. Cell Mol Life Sci. 2012; 70(3):459-73. PMC: 11113680. DOI: 10.1007/s00018-012-1062-x. View

12.

Jin L, Yu B, Liu G, Nie W, Wang J, Chen J . Mitophagy induced by UMI-77 preserves mitochondrial fitness in renal tubular epithelial cells and alleviates renal fibrosis. FASEB J. 2022; 36(6):e22342. DOI: 10.1096/fj.202200199RR. View

13.

Cortes M, Corder K, Dobrunz L . Differences between adult and adolescent male mice in approach/avoidance and expression of hippocampal NPY in response to acute footshock. Stress. 2021; 24(6):965-977. PMC: 8908778. DOI: 10.1080/10253890.2021.1976139. View

14.

Emsley J, Mitchell B, Kempermann G, Macklis J . Adult neurogenesis and repair of the adult CNS with neural progenitors, precursors, and stem cells. Prog Neurobiol. 2005; 75(5):321-41. DOI: 10.1016/j.pneurobio.2005.04.002. View

15.

Kol A, Adamsky A, Groysman M, Kreisel T, London M, Goshen I . Astrocytes contribute to remote memory formation by modulating hippocampal-cortical communication during learning. Nat Neurosci. 2020; 23(10):1229-1239. PMC: 7611962. DOI: 10.1038/s41593-020-0679-6. View

16.

Broadbent N, Squire L, Clark R . Spatial memory, recognition memory, and the hippocampus. Proc Natl Acad Sci U S A. 2004; 101(40):14515-20. PMC: 521976. DOI: 10.1073/pnas.0406344101. View

17.

Guskjolen A, Cembrowski M . Engram neurons: Encoding, consolidation, retrieval, and forgetting of memory. Mol Psychiatry. 2023; 28(8):3207-3219. PMC: 10618102. DOI: 10.1038/s41380-023-02137-5. View

18.

Akers K, Martinez-Canabal A, Restivo L, Yiu A, De Cristofaro A, Hsiang H . Hippocampal neurogenesis regulates forgetting during adulthood and infancy. Science. 2014; 344(6184):598-602. DOI: 10.1126/science.1248903. View

19.

Ben Abdallah N, Slomianka L, Vyssotski A, Lipp H . Early age-related changes in adult hippocampal neurogenesis in C57 mice. Neurobiol Aging. 2008; 31(1):151-61. DOI: 10.1016/j.neurobiolaging.2008.03.002. View

20.

Griffiths B, Bhutani A, Stary C . Adult neurogenesis from reprogrammed astrocytes. Neural Regen Res. 2019; 15(6):973-979. PMC: 7034263. DOI: 10.4103/1673-5374.270292. View