Lithium-induced effects on adult hippocampal neurogenesis are topographically segregated along the dorso-ventral axis of stressed mice

• Published in: Neuropharmacology Vol. 62; no. 1; pp. 247 - 255
• Main Authors: O’Leary, Olivia F., O’Connor, Richard M., Cryan, John F.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.01.2012
• Subjects: Analysis of Variance; Animals; Antimanic Agents - pharmacology; Antimanic Agents - therapeutic use; Body Weight - drug effects; Bromodeoxyuridine - metabolism; Cell Proliferation - drug effects; Cell Survival - drug effects; Disease Models, Animal; Dorsal hippocampus; Hippocampus - drug effects; Hippocampus - pathology; Lithium; Lithium Chloride - pharmacology; Lithium Chloride - therapeutic use; Male; Mice; Mice, Inbred BALB C; Neurogenesis; Neurogenesis - drug effects; Neurons - drug effects; Stress; Stress, Psychological - drug therapy; Stress, Psychological - pathology; Ventral hippocampus; Ventral hippocampus; Lithium; Neurogenesis; Stress; Dorsal hippocampus
• ISSN: 0028-3908; 1873-7064
• DOI: 10.1016/j.neuropharm.2011.07.015

Adult hippocampal neurogenesis is an important process in the regulation of cognition, stress responsivity, and sensitivity to antidepressant and mood stabiliser drugs. Increasing evidence suggests that the hippocampus is functionally divided along its axis with the ventral hippocampus (vHi) playing a preferential role in stress- and anxiety-related processes, while the dorsal hippocampus (dHi) is crucial for spatial learning and memory. However, it is currently unclear whether stress or the medications used to treat stress-related disorders, preferentially affect neurogenesis in the vHi rather than dHi. The aim of this study was to determine whether the mood stabiliser, lithium, preferentially affects cell proliferation and survival in the vHi rather than dHi under stress conditions. To this end, mice of the stress-sensitive strain, BALB/c, underwent chronic exposure to immobilisation stress plus lithium treatment (0.2% lithium-supplemented diet), and the rates of cell proliferation and survival were compared in the dHi and vHi. Lithium preferentially increased cell proliferation in the vHi under stress conditions only. This increase in cell proliferation was secondary to reductions in the survival of newly-born cells. Moreover, lithium-induced decreases in cell survival in the vHi were only observed under stress conditions. Taken together, the data suggest that the turnover of newly-born cells in response to chronic stress and lithium treatment occurs predominantly in the vHi rather than the dHi. This article is part of a Special Issue entitled ‘Anxiety and Depression’. ► Lithium increases hippocampal cell proliferation in stressed BALB/c mice. ► This effect occurs preferentially in the vHi but not dHi and in stressed mice only. ► Increases in proliferation are secondary to reduced survival of newly-born cells. ► Lithium reduced cell survival in the vHi under stress conditions only.