| First Author | Ueda H | Year | 2017 |
| Journal | J Neurochem | Volume | 141 |
| Issue | 1 | Pages | 124-136 |
| PubMed ID | 28122138 | Mgi Jnum | J:240549 |
| Mgi Id | MGI:5887153 | Doi | 10.1111/jnc.13963 |
| Citation | Ueda H, et al. (2017) Prothymosin alpha-deficiency enhances anxiety-like behaviors and impairs learning/memory functions and neurogenesis. J Neurochem 141(1):124-136 |
| abstractText | Prothymosin alpha (ProTalpha) is expressed in various mammalian organs including the neuronal nuclei in the brain, and is involved in multiple functions, such as chromatin remodeling, transcriptional regulation, cell proliferation, and survival. ProTalpha has beneficial actions against ischemia-induced necrosis and apoptosis in the brain and retina. However, characterizing the physiological roles of endogenous ProTalpha in the brain without stress remains elusive. Here, we generated ProTalpha-deficiency mice to explore whether endogenous ProTalpha is involved in normal brain functions. We successfully generated heterozygous ProTalpha knockout (ProTalpha+/- ) mice, while all homozygous ProTalpha knockout (ProTalpha-/- ) offspring died at early embryonic stage, suggesting that ProTalpha has crucial roles in embryonic development. In the evaluation of different behavioral tests, ProTalpha+/- mice exhibited hypolocomotor activity in the open-field test and enhanced anxiety-like behaviors in the light/dark transition test and the novelty induced hypophagia test. ProTalpha+/- mice also showed impaired learning and memory in the step-through passive avoidance test and the KUROBOX test. Depression-like behaviors in ProTalpha+/- mice in the forced swim and tail suspension tests were comparable with that of wild-type mice. Furthermore, adult hippocampal neurogenesis was significantly decreased in ProTalpha+/- mice. ProTalpha+/- mice showed an impaired long-term potentiation induction in the evaluation of electrophysiological recordings from acute hippocampal slices. Microarray analysis revealed that the candidate genes related to anxiety, learning/memory-functions, and neurogenesis were down-regulated in ProTalpha+/- mice. Thus, this study suggests that ProTalpha has crucial physiological roles in the robustness of brain. |
