Abstract
The behavior of female rats changes profoundly as they become mothers. The brain region that plays a central role in this regulation is the preoptic area, and lesions in this area eliminates maternal behaviors in rodents. The molecular background of the behavioral changes has not been established yet; therefore, in the present study, we applied proteomics to compare protein level changes associated with maternal care in the rat preoptic area. Using 2-dimensional fluorescence gel electrophoresis followed by identification of altered spots with mass spectrometry, 12 proteins were found to be significantly increased, and 6 proteins showed a significantly reduced level in mothers. These results show some similarities with a previous proteomics study of the maternal medial prefrontal cortex and genomics approaches applied to the preoptic area. Gene ontological analysis suggested that most altered proteins are involved in glucose metabolism and neuroplasticity. These proteins may support the maintenance of increased neuronal activity in the preoptic area, and morphological changes in preoptic neuronal circuits are known to take place in mothers. An increase in the level of alpha-crystallin B chain (Cryab) was confirmed by Western blotting. This small heat shock protein may also contribute to maintaining the increased activity of preoptic neurons by stabilizing protein structures. Common regulator and target analysis of the altered proteins suggested a role of prolactin in the molecular changes in the preoptic area. These results first identified the protein level changes in the maternal preoptic area. The altered proteins contribute to the maintenance of maternal behaviors and may also be relevant to postpartum depression, which can occur as a molecular level maladaptation to motherhood.
Highlights
An altered physiological state is characteristic of mothers in mammals, which is required for the support of the young offspring
We identified the following proteins as regulators of several of the maternally altered proteins (Fig. 4) using common regulator analysis: Transcription factor E2f (E2f), Transcription factor AP-1/Proto-oncogene c-Fos (Jun/Fos), Platelet-derived growth factor (Pdgf), Phosphatidylinositol-3-kinases (Pi3k), Rac-alpha serine/threonine-protein kinase (Akt1), Serine/ threonine-protein kinase mTOR (Mtor), Peptidyl-prolyl cis–trans isomerase NIMA-interacting 1 (Pin1), Thioredoxin (Txn), Heat shock factor protein 1 (Hsf1), Cyclic AMP-responsive element-binding protein 1 (Creb1), Early growth response protein 1 (Egr1), Myc proto-oncogene protein (Myc), Hypoxia-inducible factor 1-alpha (Hif1A), Transcription factor Sp1 (Sp1), Signal transducer and activator of transcription 3 (Stat3), Cellular tumor antigen p53 (Tp53), Insulin (Ins), and Transforming growth factor beta-1 (Tgfb1)
Additional pathways, e.g., those resulting from increased neuronal activity as a result of input from the pups, cannot be excluded either, as only a portion of the activated neurons in the mPOA respond to prolactin [5, 64]. These results are the first to indicate that protein level changes take place in the preoptic area (POA) as it adapts to the maternal challenges facing female rats in the postpartum period
Summary
An altered physiological state is characteristic of mothers in mammals, which is required for the support of the young offspring. Mother rats take care of the pups; they lactate, respond to the pups, retrieve them to the nest and nurse them, and they protect them against intruders by a process called maternal aggression [1, 2]. Rat mothers have emotional alterations during the postpartum period. They show reduced anxiety and antidepressant-like behaviors in situations unrelated to the pups and demonstrate hyporesponsiveness to stressors in their hypothalamo-pituitary-adrenal axis [1, 2]. The profound physiological, endocrine, and emotional changes in the maternal brain have led us to suggest an altered protein pattern in relevant brain areas. While lactation is controlled by prolactin and oxytocin release that is regulated by neurons located in the hypothalamic arcuate
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