LAUSR

BACKGROUND Early life and stressful experiences affect hippocampal and amygdala structure and function. They also increase the incidence of mental and nervous system disorders in adults. However, prospective studies have yet to show if early-life experiences affect the risk/severity of post-traumatic stress disorder (PTSD). METHODS We applied neonatal isolation (NI) alone, single prolonged stress (SPS) alone and NI + SPS to rats. We evaluated anxiety-like behavior and spatial memory of behavior using open field, elevated plus maze, and Morris water maze tests. Then, we measured expression of glucocorticoid receptors (GRs) and synaptic-related proteins by immunofluorescence, immunohistochemistry and western blotting in the hippocampus and amygdala. RESULTS NI + SPS exacerbated the increased anxiety levels and impaired spatial memory induced by NI alone or SPS alone. NI alone or SPS alone induced varying degrees of change in expression of GRs and synaptic proteins (synapsin I and postsynaptic density protein-95) in the hippocampus and amygdala. There were opposite changes in GR expression in the hippocampal dentate gyrus and basolateral amygdala. The degree of such change was exacerbated considerably by NI + SPS. In addition, neuroligin (NLG)-1 and NLG-2 were distributed in postsynaptic sites of excitatory and inhibitory synapses, respectively. NI, SPS, and NI + SPS altered the patterns of NLG-1 and NLG-2 colocalization as well as their intensity. NI + SPS strengthened the increased ratio of NLG-1/NLG-2 in the hippocampus, but decreased this ratio in the amygdala. CONCLUSIONS NI and SPS together induced greater degrees of change in anxiety and spatial memory, as well as GR and synaptic protein levels, in the hippocampus and amygdala than the changes induced by NI alone or SPS alone.