Rapid communication Presenilin 1 and 2 are expressed differentially in the cerebral cortex of mice during development Ashish Kumar, M.K. Thakur ⇑ Biochemistry and Molecular Biology Laboratory, Brain Research Centre, Department of Zoology, Banaras Hindu University, Varanasi 221 005, India article info Article history: Received 13 March 2012 Received in revised form 12 June 2012 Accepted 2 July 2012 Available online 11 July 2012 Keywords: PS expression Neurogenesis Synaptogenesis Brain development abstract Presenilin (PS) 1 and PS2 are multi-pass transmembrane proteins involved in vital brain functions. Stud- ies using transgenic or conditional knockout models show that PS1 is implicated in crucial brain devel- opmental processes. Conversely, PS2 knockout mice do not exhibit any abnormality in the brain morphology, suggesting that PS2 may not be involved in brain development. However, there is no holistic information available for endogenous expression of PS during brain development. Therefore, we have examined the distribution and expression profile of PS1 and PS2 mRNA and protein in the cerebral cortex of prenatal, neonatal and postnatal mice. The results revealed that the distribution and expression profile of PS1 and PS2 mRNA varied significantly in the cerebral cortex during development. In prenatal stages, both PS1 and PS2 mRNA showed high expression at embryonic day (E) 12.5 and downregulation at E18.5. Postnatally, PS1 mRNA showed upregulation from postnatal day 0 (P0) to P45 and thereafter reduction at 20 weeks, but PS2 mRNA showed no significant alteration. However, they did not exhibit any significant regional variation except at E18.5, when PS2 showed reduction in temporal and medial temporal lobes as compared to frontal and parietal lobes. Furthermore, PS1 showed significant change in protein expression similar to its mRNA profile. However, PS2 protein expression did not correspond to its mRNA; it was high- est at E12.5, downregulated up to P20 and then upregulated at P45 and 20 weeks. Taken together, our study demonstrates for the first time that the distribution and expression profile of PS2 is different from PS1 in the mouse cerebral cortex during development. Ó 2012 Elsevier Ltd. All rights reserved. 1. Introduction Brain development is an extremely synchronized cascade of sequential and concomitant events starting from early gestation and continuing after birth through adulthood. This cascade is tightly regulated by the coordinated expression and function of sev- eral genes. The present study deals with two such genes, Presenilin (PS) 1 and PS2 belonging to aspartyl protease family of multi-pass transmembrane proteins. Both PS1 and PS2 are widely expressed in the central nervous system and peripheral tissues with some de- gree of regional variation. They also show remarkable homology in the sequence of their genes, transcripts and proteins. Their full length proteins are highly unstable and undergo endoproteolysis to produce 32 kDa N-terminal fragment (NTF) and 20 kDa C- terminal fragment (CTF) (Ratovitski et al., 1997). NTFs regulate most of the proteolytic functions of PS through c-secretase complex which is composed of PS NTFs as catalytic core, aph-1, nicastrin and pen-2 (Uchihara et al., 2006). PS1 knockout mice exhibit severe defects in cerebral cortex (Wen et al., 2005) and death at intrauterine life, suggesting its vi- tal role in cerebral cortex development. PS1 is involved in several processes such as neurogenesis, neuronal differentiation, neuronal migration, cortical lamination (Wines-Samuelson et al., 2005) and synaptogenesis (Uchihara et al., 2006). On the contrary, PS2 knockout mice do not show any abnormality in the brain mor- phology (Herreman et al., 1999), suggesting that PS2 may not be involved in brain development, rather it might be involved in other physiological functions or act as a compensatory partner of PS1 after birth in various signaling pathways (Wang et al., 2003). Most of the studies done so far are based on conditional knockouts, transgenic mice or specific cell lines of PS. However, no holistic information is available on PS expression during brain development under normal physiological conditions. Therefore, we have analyzed the distribution and expression profile of PS1 and PS2 in normal mouse cerebral cortex during prenatal, neona- tal and postnatal stages of development. We have used cerebral cortex as it is the largest part of brain, developing from telen- cephalon and implicated in major brain functions including sen- sory, perception and cognition. 0197-0186/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.neuint.2012.07.001 ⇑ Corresponding author. Tel.: +91 542 2313958; fax: +91 542 2368174. E-mail address: mkt_bhu@yahoo.com (M.K. Thakur). Neurochemistry International 61 (2012) 778–782 Contents lists available at SciVerse ScienceDirect Neurochemistry International journal homepage: www.elsevier.com/locate/nci