Insights into aging of the hippocampus: A view from the topographic differentiation

Abstract

More than fifty years ago, a number of studies reported the reduction of neuron numbers related to brain aging. However, later studies have concluded that the neuronal loss due to aging is limited to specific regions of the nervous system and its significance is irrelevant in both humans and non-human mammals. Instead, several other mechanisms that may underlie brain aging have attracted attention in the field of neuroscience research. Namely, some papers have indicated the relationship between memory impairment and decline in adult neurogenesis in the hippocampus during aging. It has also been reported that abnormalities of oligodendrogenesis in the mature brain may be involved in age-related cognitive decline. We herein briefly review recent findings on age-related changes in adult neurogenesis and oligodendrogenesis, and discuss their functional significance from the view point of topography of the hippocampus. Namely, the hippocampus has shown to be structurally and functionally differentiated along the longitudinal and transverse axes. In the rodent brain, the dorsal (septal) hippocampus is involved in cognition, learning, and memory, while the ventral (temporal) hippocampus contributes to regulation of emotion, mood, and anxiety. Nevertheless, the question of how topographic differentiation of the hippocampus might be affected by aging still remains largely unanswered. Our latest studies have shown that the waning of adult neurogenesis and oligodendrogenesis during aging is more relevant in the ventral hippocampus than in the dorsal hippocampus. We therefore hypothesize that the ventral-dominant decline in hippocampal neurogenesis and oligodendrogenesis may partly explain why major depression frequently precedes dementia in elderly people. These findings provide new insights into aging of the hippocampus.