A reduced number of hippocampal granule cells does not associate with an anhedonia-like phenotype in a rat chronic mild stress model of depression

Abstract

Several clinical and preclinical studies have indicated that hippocampal shrinkage and decreased neurogenesis are implicated in the pathology of depression. Recent animal studies have shown, however, that the development of depression-related symptoms may take place through neurogenesis-independent pathways. To evaluate whether the stress-induced morphological changes in the hippocampal formation are causally related to the development of anhedonia-like symptoms, we combined the chronic mild stress (CMS) rat model of depression with stereological estimations of the number of proliferating progenitors, the total number of granule cells, and the volume of the ventral hippocampal formation (VHF). First, we found that stress-susceptible and stress-resilient animals, as categorized according to the behavioral read-out, both have a decrease in hippocampal cell proliferation. Our results also indicated that the anhedonia-like state in CMS rats develops prior to maximal suppression of cell proliferation, but correlates with a reduction in the total number of granule cells in the VHF. Furthermore, recovery from depression-related symptoms correlated with re-establishment of proliferation rates, but not with the total number of granule cells. Notably, decreases in the number of granule cells occurred independently of the induction of an anhedonia-like phenotype. There were no stress-induced changes in the volume of the VHF. We conclude that cell proliferation and a reduction in the total number of granule cells in the VHF are triggered by chronic stress, but do not associate with development of an anhedonia-like state in rats.

Keywords::

• Bromodeoxyuridine
• chronic stress
• depression
• hippocampus
• neurogenesis
• stereology

Acknowledgements

We thank Phine Katrine Kjær Wiborg and Stine Dhiin for skillful technical assistance. This work was supported by the Lundbeck Foundation. All the procedures involving animals were approved by Danish National Committee for Ethics in Animal Experimentation (2002/561-575).

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.