Acute and long-term effects of adolescence stress exposure on rodent adult hippocampal neurogenesis, cognition, and behaviour

Abstract

Adolescence represents a critical period for brain and behavioural health and characterised by the onset of mood, psychotic and anxiety disorders. In rodents, neurogenesis is very active during adolescence, when is particularly vulnerable to stress. Whether stress-related neurogenesis changes influence adolescence onset of psychiatric symptoms remains largely unknown. A systematic review was conducted on studies investigating changes in hippocampal neurogenesis and neuroplasticity, hippocampal-dependent cognitive functions, and behaviour, occurring after adolescence stress exposure in mice both acutely (at post-natal days 21-65) and in adulthood. A total of 37 studies were identified in the literature. Seven studies showed reduced hippocampal cell proliferation, and out of those two reported increased depressive-like behaviours, in adolescent rodents exposed to stress. Three studies reported a reduction in the number of new-born neurons, which however were not associated with changes in cognition or behaviour. Sixteen studies showed acutely reduced hippocampal neuroplasticity, including pre- and post-synaptic plasticity markers, dendritic spine length and density, and long-term potentiation after stress exposure. Cognitive impairments and depressive-like behaviours were reported by 11 of the 16 studies. Among studies who looked at adolescence stress exposure effects into adulthood, seven showed that the negative effects of stress observed during adolescence on either cell proliferation or hippocampal neuroplasticity, cognitive deficits and depressive-like behaviour, had variable impact in adulthood. Treating adolescent mice with antidepressants, glutamate receptor inhibitors, glucocorticoid antagonists, or healthy diet enriched in omega-3 fatty acids and vitamin A, prevented or reversed those detrimental changes. Future research should investigate the translational value of these preclinical findings. Developing novel tools for measuring hippocampal neurogenesis in live humans, would allow assessing neurogenic changes following stress exposure, investigating relationships with psychiatric symptom onset, and identifying effects of therapeutic interventions.

Fig. 1. Schematic representation of the effects of stress exposure on rodent hippocampal neurogenesis, neuroplasticity, cognitive functions and depressive-like behaviours during adolescence (PND 21–65) and adulthood (PND66–90).

Changes (increase or decrease) in the aforementioned outcomes are indicated with arrows. Legend: increase (↑) or decrease (↓).

Fig. 2. Schematic representation of the beneficial effect of treatment with either omega-3 fatty acids, vitamin A, antidepressants, glutamate receptor inhibitors or glucocorticoid receptor antagonists on rodent hippocampal neurogenesis, neuroplasticity, cognitive functions and depressive-like behaviours during adolescence (PND21–65) and adulthood (PND66–90).

Changes (increase or decrease) in the aforementioned outcomes are indicated with arrows. Legend: increase (↑) or decrease (↓).