ATP6AP2 over-expression causes morphological alterations in the hippocampus and in hippocampus-related behaviour

• Published in: Brain Structure and Function Vol. 223; no. 5; pp. 2287 - 2302
• Main Authors: Bracke, A., Schäfer, S., von Bohlen und Halbach, V., Klempin, F., Bente, K., Bracke, K., Staar, D., van den Brandt, J., Harzsch, S., Bader, M., Wenzel, U. O., Peters, J., von Bohlen und Halbach, O.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.06.2018; Springer Nature B.V
• Subjects: Adenosine triphosphatase; Anatomy; Animals; Behavior, Animal - physiology; Biomedical and Life Sciences; Biomedicine; Brain architecture; Cell Biology; Cell cycle; Cell Cycle - genetics; Cell growth; Cell proliferation; Cell Proliferation - genetics; Cerebral Ventricles - anatomy & histology; Cognitive ability; Dark Adaptation - genetics; Dendritic spines; Dendritic Spines - metabolism; Ependyma - metabolism; Exploratory Behavior; Hippocampus; Hippocampus - cytology; Hippocampus - diagnostic imaging; Hippocampus - physiology; Histones - metabolism; Maze Learning - physiology; Mice; Mice, Transgenic; Microtubule-Associated Proteins - metabolism; Morphology; Mutation; Neural stem cells; Neurogenesis; Neurogenesis - genetics; Neurology; Neurons - cytology; Neuropeptides - metabolism; Neurosciences; Original Article; Overexpression; Pattern recognition; Proton-Translocating ATPases - genetics; Proton-Translocating ATPases - metabolism; Receptors, Cell Surface - genetics; Receptors, Cell Surface - metabolism; Recognition (Psychology) - physiology; Renin; Sex Characteristics; Stem cell transplantation; Stem cells; Transgenic mice; Ventricle; Micro-CT; (Pro)renin receptor; Dendritic spines; Behaviour; Adult neurogenesis; Cilia
• ISSN: 1863-2653; 1863-2661; 0340-2061
• DOI: 10.1007/s00429-018-1633-1

The (pro)renin receptor [(P)RR], also known as ATP6AP2 [ATPase 6 accessory protein 2], is highly expressed in the brain. ATP6AP2 plays a role in early brain development, adult hippocampal neurogenesis and in cognitive functions. Lack of ATP6AP2 has deleterious effects, and mutations of ATP6AP2 in humans are associated with, e.g. X-linked intellectual disability. However, little is known about the effects of over-expression of ATP6AP2 in the adult brain. We hypothesized that mice over-expressing ATP6AP2 in the brain might exhibit altered neuroanatomical features and behavioural responses. To this end, we investigated heterozygous transgenic female mice and confirmed increased levels of ATP6AP2 in the brain. Our data show that over-expression of ATP6AP2 does not affect adult hippocampal neurogenesis, exercise-induced cell proliferation, or dendritic spine densities in the hippocampus. Only a reduced ventricular volume on the gross morphological level was found. However, ATP6AP2 over-expressing mice displayed altered exploratory behaviour with respect to the hole-board and novel object recognition tests. Moreover, primary adult hippocampal neural stem cells over-expressing ATP6AP2 exhibit a faster cell cycle progression and increased cell proliferation. Together, in contrast to the known deleterious effects of ATP6AP2 depletion, a moderate over-expression results in moderate behavioural changes and affects cell proliferation rate in vitro.