Chronic stress targets adult neurogenesis preferentially in the suprapyramidal blade of the rat dorsal dentate gyrus
- 451 Downloads
The continuous generation of new neurons and glial cells in the adult hippocampal dentate gyrus (DG) represents an important form of adult neuroplasticity, involved in normal brain function and behavior but also associated with the etiopathogenesis and treatment of psychiatric disorders. Despite the large number of studies addressing cell genesis along the septotemporal axis, data on the anatomical gradients of cytogenesis along the DG transverse axis is scarce, especially after exposure to stress. As such, in this study we characterized both basal proliferation and survival of adult-born neural cells along the transverse axis of the rat dorsal DG, and after stress exposure. In basal conditions, both proliferating cells and newborn neurons and glial cells were preferentially located at the subgranular zone and suprapyramidal blade. Exposure to chronic stress induced an overall decrease in the generation of adult-born neural cells and, more specifically, produced a regional-specific decrease in the survival of adult-born neurons at the suprapyramidal blade. No particular region-specific alterations were observed on surviving adult-born glial cells. This work reveals, for the first time, a distinct survival profile of adult-born neural cells, neurons and glial cells, among the transverse axis of the DG, in both basal and stress conditions. Our results unveil that adult-born neurons are preferentially located in the suprapyramidal blade and suggest a regional-specific impact of chronic stress in this blade with potential repercussions for its functional significance.
KeywordsDentate gyrus Transverse axis Cytogenesis Proliferation Survival Chronic stress
Compliance with ethical standards
NDA, PP, AMP, ARMS, MM and LP received fellowships from the Portuguese Foundation for Science and Technology (FCT). This work was funded by FCT (IF/01079/2014). This article has been developed under the scope of the project NORTE-01-0145-FEDER-000013, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER). This work has been funded by FEDER funds, through the Competitiveness Factors Operational Programme (COMPETE), and by National funds, through the Foundation for Science and Technology (FCT), under the scope of the project POCI-01-0145-FEDER-007038.
Conflict of interest
The authors declare no conflicts of interest.
- de Bruin JP, Sanchez-Santed F, Heinsbroek RP, Donker A, Postmes P (1994) A behavioural analysis of rats with damage to the medial prefrontal cortex using the Morris water maze: evidence for behavioural flexibility, but not for impaired spatial navigation. Brain Res 652:323–333CrossRefPubMedGoogle Scholar
- Kesner RP (2000) Behavioral analysis of the contribution of the hippocampus and parietal cortex to the processing of information: interactions and dissociations. Hippocampus 10:483–490. doi: 10.1002/1098-1063(2000)10:4<483:AID-HIPO15>3.0.CO;2-Z CrossRefPubMedGoogle Scholar
- Kocsis B, Vertes RP (1997) Phase relations of rhythmic neuronal firing in the supramammillary nucleus and mammillary body to the hippocampal theta activity in urethane anesthetized rats. Hippocampus 7:204–214. doi: 10.1002/(SICI)1098-1063(1997)7:2<204:AID-HIPO7>3.0.CO;2-M CrossRefPubMedGoogle Scholar
- Kuhn HG, Biebl M, Wilhelm D, Li M, Friedlander RM, Winkler J (2005) Increased generation of granule cells in adult Bcl-2-overexpressing mice: a role for cell death during continued hippocampal neurogenesis. Eur J Neurosci 22:1907–1915. doi: 10.1111/j.1460-9568.2005.04377.x CrossRefPubMedGoogle Scholar
- Nieto-Estevez V, Oueslati-Morales CO, Li L, Pickel J, Morales AV, Vicario-Abejon C (2016) Brain insulin-like growth factor-I directs the transition from stem cells to mature neurons during postnatal/adult hippocampal neurogenesis. Stem Cells 34:2194–2209. doi: 10.1002/stem.2397 CrossRefPubMedGoogle Scholar
- Nollet M, Gaillard P, Tanti A, Girault V, Belzung C, Leman S (2012) Neurogenesis-independent antidepressant-like effects on behavior and stress axis response of a dual orexin receptor antagonist in a rodent model of depression. Neuropsychopharmacology 37:2210–2221. doi: 10.1038/npp.2012.70 CrossRefPubMedPubMedCentralGoogle Scholar
- O’Keefe J, Nadel L (1978) The hippocampus as a cognitive map. Clarendon Press, OxfordGoogle Scholar
- Pace TW, Gaylord R, Topczewski F, Girotti M, Rubin B, Spencer RL (2005) Immediate-early gene induction in hippocampus and cortex as a result of novel experience is not directly related to the stressfulness of that experience. Eur J Neurosci 22:1679–1690. doi: 10.1111/j.1460-9568.2005.04354.x CrossRefPubMedGoogle Scholar
- VanElzakker M, Fevurly RD, Breindel T, Spencer RL (2008) Environmental novelty is associated with a selective increase in Fos expression in the output elements of the hippocampal formation and the perirhinal cortex. Learn Mem 15:899–908. doi: 10.1101/lm.1196508 CrossRefPubMedPubMedCentralGoogle Scholar