Impaired learning and memory in CD38 null mutant mice.

Somi Kim,Jae-Ick Kim,Bong-Kiun Kaang,Taehyun Kim,Juyoun Yoo,Sang Jeong Kim,So-Young Rah,Hyun-Hee Ryu,Bolam Lee,Chae Seok Lim,Hye-Ryeon Lee,Eun-Hye Jang,Yong-Seok Lee,Uh-Hyun Kim,Minkyung Kang

doi:10.1186/s13041-016-0195-5

Abstract

CD38 is an enzyme that catalyzes the formation of cyclic ADP ribose and nicotinic acid adenine dinucleotide phosphate, both of which are involved in the mobilization of Ca2+ from intracellular stores. Recently, CD38 has been shown to regulate oxytocin release from hypothalamic neurons. Importantly, CD38 mutations are associated with autism spectrum disorders (ASD) and CD38 knockout (CD38−/−) mice display ASD-like behavioral phenotypes including deficient parental behavior and poor social recognition memory. Although ASD and learning deficits commonly co-occur, the role of CD38 in learning and memory has not been investigated. We report that CD38−/− mice show deficits in various learning and memory tasks such as the Morris water maze, contextual fear conditioning, and the object recognition test. However, either long-term potentiation or long-term depression is not impaired in the hippocampus of CD38−/− mice. Our results provide convincing evidence that CD38−/− mice show deficits in various learning and memory tasks including spatial and non-spatial memory tasks. Our data demonstrate that CD38 is critical for regulating hippocampus-dependent learning and memory without modulating synaptic plasticity.Electronic supplementary materialThe online version of this article (doi:10.1186/s13041-016-0195-5) contains supplementary material, which is available to authorized users.

Highlights

CD38 is an Adenosine diphosphate (ADP)-ribosyl cyclase that catalyzes the formation of cyclic ADP ribose and nicotinic acid adenine dinucleotide phosphate, which are involved in the mobilization of Ca2+ from intracellular stores [1,2,3]
Hippocampus-dependent memory is impaired in CD38−/− To examine whether deletion of CD38 affects learning and memory, we tested CD38−/− mice in the Morris water maze test, which requires intact hippocampal function [16, 17]
The knockouts took significantly longer to reach the hidden platform compared to their wild-type (WT) littermates in the training trials [CD38+/+, n = 9; CD38−/−, n = 13; twoway analysis of variance (ANOVA), interaction between genotype and day, F4, 344 = 2.529, * p < 0.05; Fig. 1a]

Summary

Introduction

CD38 is an ADP-ribosyl cyclase that catalyzes the formation of cyclic ADP ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate, which are involved in the mobilization of Ca2+ from intracellular stores [1,2,3]. CD38 has been shown to regulate oxytocin (OXT) release from hypothalamic neurons by modulating intracellular Ca2+ mobilization [5, 6]. Studies have shown that CD38−/− mice display autism spectrum disorder (ASD)-like behavioral phenotypes that can be reversed with OXT treatment [6, 7] and mutations in CD38 are associated with ASD in human patients [8, 9]. It is known that OXT neurons in the hypothalamus send their projections to the hippocampus wherein OXT receptors are highly expressed [11,12,13] and that OXT regulates hippocampal synaptic plasticity [14, 15], it remains largely unknown whether CD38 deletion affects hippocampal synaptic plasticity and hippocampus-dependent learning and memory

Methods

Results

Conclusion