Why are maternally separated females inflexible? Brain activity pattern of COx and c-Fos

Abstract

Subjects' early life events will affect them later in life. When these events are stressful, such as child abuse in humans or repeated maternal separation in rodents, subjects can show some behavioral and brain alterations. This study used young adult female Wistar rats that were maternally raised (AFR), maternally separated from post-natal day (PND) 1 to PND10 (MS10), or maternally separated from PND1 to PND21 (MS21), in order to assess the effects of maternal separation (MS) on spatial learning and memory, as well as cognitive flexibility, using the Morris Water Maze (MWM). We performed quantitative cytochrome oxidase (COx) histochemistry on selected brain areas in order to identify whether maternal separation affects brain energy metabolism. We also performed c-Fos immunohistochemistry on the medial prefrontal cortex (mPFC), thalamus, and hippocampus to explore whether this immediate early gene activity was altered in stressed subjects. We obtained a similar spatial learning pattern in maternally raised and maternally separated subjects on the reference memory task, but only the controls were flexible enough to solve the reversal learning successfully. Separated groups showed less c-Fos activity in the mPFC and less complex neural networks on COx.

Sex-Specific Effects of Early Life Stress on Brain Mitochondrial Function, Monoamine Levels and Neuroinflammation

“…In particular, early MS during the two first weeks of life in rats seems to impair adult HPA axis response, because it overlaps with the ‘stress-hyporesponsive period’ (SHRP, PND 3-14 in rats) characterized by low ACTH and glucocorticoid levels in response to external stressors [ 7 , 32 ]. However, prolonged MS during the entire lactation period (PND 1-21) in rodents may have different effects on the HPA axis function during adulthood, as already reported regarding brain CCO activity [ 34 , 35 ]. Accordingly, increased brain CCO activity in MS female rats as compared to same-sex controls was reported using a short MS period (PND 1-10) that only partially overlapped the SHRP [ 35 ].…”

“…The litters were randomly distributed in two groups as previously described [ 35 , 36 , 38 , 39 ]: maternal separation (MS) group with daily separation of the whole litter in an incubator at 30 °C during 4 h from P1 through P21, and control group with unhandled litters during the same time period. After weaning on P21, male and female pups were removed and housed separately in groups of 4 to 5 animals per cage until adulthood (P90).…”

“…Given the paucity of studies about sex differences in the long-term effects of ELS on brain mitochondrial function, neurochemistry, and neuroinflammation, the present study aimed to evaluate these effects after prolonged MS in male and female rats over the entire weaning period (PND 1-21, 4 h/day) [ 34 , 35 , 36 , 37 , 38 , 39 ]. Evaluation of brain mitochondrial function was performed by quantification of regional brain oxidative metabolic capacity using cytochrome c oxidase (CCO) quantitative histochemistry.…”

“…Changes in brain CCO activity are directly coupled with changes in neuronal activity in order to meet its energy demands [ 40 ]. Quantitative CCO histochemistry in brain tissue has been applied in previous studies using several MS protocols in male or female rodents by our research group and others [ 32 , 34 , 35 , 41 ]. Brain oxidative capacity in selected regions of interest (prelimbic and infralimbic areas of the prefrontal cortex, cingulate cortex, dorsal and ventral hippocampus, and striatum) will be evaluated in adult (70-day-old) male and female rats after early prolonged MS as already described.…”

Adult social isolation leads to anxiety and spatial memory impairment: Brain activity pattern of COx and c-Fos

“…The control group (C) (n=8) consisted of rats that remained grouped (4 per cage) in their home box (56x33x20 cm) and were housed in the same place for the same time period as the experimental group. Eight animals per group were used for the behavioural assessment and COx histochemistry, whereas 6 animals per group were randomly selected for c-Fos immunohistochemistry, based on previous literature [37].…”