An animal study connects learning to cope with mild stress to improved spatial learning and increased hippocampal neurogenesis.
Animal studies have shown increased hippocampal neurogenesis with antidepressant use (Proc Natl Acad Sci U S A 2001; 98:12796), but less is known about the hippocampal effects of coping with naturally occurring stress, which would have implications for nonpharmacological psychiatric treatments. To test the effect of coping with stress on hippocampal neurogenesis and hippocampal-related behaviors, these researchers used an animal model that mimics coping with naturally occurring environmental stress.
Twelve male monkeys were randomized to either living for 18 months with the same male partner (nonstressed control group) or to six 3-month sessions, in which monkeys spent the first 3 weeks in isolation and the last 9 weeks with a new male partner (stressed experimental group). The experimental condition is similar to these monkeys’ typical social environment, in which males compete for inclusion in groups with females.
To measure hippocampal function, researchers trained the monkeys in a spatial learning task involving food retrieval. During the last session of the experiment, all monkeys received a marker for neurogenesis (BrdU). At study’s end, monkey brains were examined for uptake of BrdU (a measure of new cell formation), uptake of a marker for mature neurons (NeuN), and gene expression. Compared with controls, experimental monkeys exhibited significantly higher spatial learning and 44% more hippocampal neurogenesis, measured by the number of neurons double-labeled with BrdU and NeuN. Activation of five genes related to neuronal functioning was significantly different between cases and controls. In both groups, more than 85% of new cells stained positive for NeuN, an indication that the new cells had become mature neurons.
Comment: The neurogenesis in these primates suggests that coping with stress might also produce neurogenesis in people. The findings also suggest that nondrug stress-coping interventions for mood and anxiety disorders would lead to hippocampal neurogenesis, similar to that seen with antidepressant use. Clinicians can be encouraged that their nondrug interventions may well be producing improved hippocampal morphology and function similar to that seen with pharmacological agents.
— Barbara Geller, MD
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