From Isolation to Impairment: Hippocampal Plasticity Changes in Adult Females

Pereda-Pérez I, Popović N, Otalora BB, Popović M, Madrid JA, Rol MA, Venero C. Long-term social isolation in the adulthood results in CA1 shrinkage and cognitive impairment. Neurobiol Learn Mem 2013;106:31-39. doi: 10.1016/j.nlm.2013.07.004.

Background: Social isolation in adulthood is a significant psychosocial stressor that can alter brain structure and function. Previous research has produced inconsistent findings regarding its effects on learning and memory, particularly in fear conditioning, while the underlying neural mechanisms remain unclear. Neural cell adhesion molecule (NCAM) and its polysialylated form (PSA-NCAM) are key modulators of synaptic plasticity and memory processes, suggesting they could mediate the cognitive effects of isolation.

Hypothesis: This study hypothesized that prolonged social isolation in adult female Octodon degus would impair hippocampus-dependent contextual fear memory, potentially through alterations in hippocampal PSA-NCAM expression and morphology.

Methods: The authors exposed adult female degus to six and a half months of individual or group housing. Fear conditioning was assessed using freezing behavior to contextual and auditory cues. After behavioral testing, hippocampal tissue was processed for volumetric analysis using Stereo Investigator to estimate total, CA1 and CA3 volumes. Synaptic and total levels of NCAM, PSA-NCAM, and NMDA receptor subunits were quantified by Western blot and ELISA. Additional physiological measures included plasma cortisol, adrenal weight and full blood counts.

Results: Isolated degus showed reduced contextual but normal auditory fear memory. Synaptic PSA-NCAM, but not NCAM, was significantly decreased in the hippocampus of isolated animals. CA1, but not CA3 or total hippocampal, volume was reduced. Isolated animals also exhibited diminished body weight gain and fewer granulocytes, while cortisol and adrenal weights were unaffected.

Conclusions: Long-term social isolation in adult female degus caused CA1 shrinkage and reduced hippocampal PSA-NCAM levels, correlating with impaired contextual fear memory. These findings indicate that isolation induces specific hippocampal alterations linked to cognitive and immune dysfunctions.