Psychomotor activation levels in mice are regulated by vasoactive intestinal peptide produced by bone marrow derived blood cells Pubblico
Panjwani, Reema (2016)
Abstract
Produced by both neurons and lymphocytes, vasoactive intestinal peptide (VIP) is a 28-amino acid neuropeptide that decreases Th1 and anti-viral immunity. VIP also plays a role in regulating neurological behavior; previous investigations have determined that VIP/peptide histidine isoleucine knockout (VIP-KO) mice exhibit altered circadian rhythms, decreased mobility, and selective cognitive disabilities. The goal of this study was to understand the role of VIP in murine behavior and determine whether VIP produced by bone marrow-derived blood cells influence neurological function. This question was addressed using radiation chimeras of female C57BL/6J VIP-KO and wild-type (WT) mice receiving syngeneic transplants of bone marrow derived cells from either VIP-KO or WT donors. We hypothesized that the behaviors of VIP-KO mice will be changed to resemble wild-type mice in radiation chimeras engrafted with hematopoietic cells from WT mice and the behavior of wild type mice will be changed to resemble VIP-KO mice in radiation chimeras of WT mice engrafted with hematopoietic cells from VIP KO mice. Mice were observed for circadian rhythms, examined during forced swim tests (FST), and tested in contextual fear conditioning (CFC) paradigms 10-weeks post-transplant. Our hypothesis was supported and a difference was noted between transplant groups receiving WT and KO hematopoietic cells. Chimeras receiving KO bone marrow-derived cells exhibited significantly greater novelty induced locomotion. Wild type chimeras engrafted with KO cells showed significantly greater dark phase activity and swam significantly more during the FST. No difference was measured in the freeze response among radiation chimeras during the CFC. These findings indicate bone marrow-derived blood cells influence behavior and that VIP produced by blood cells is important in psychomotor activation levels. Future investigations include repeating experiments with male models and analyzing VIP content and brain histology to determine neurological function during behavioral testing.
Table of Contents
INTRODUCTION. 1
VIP's Function in the Immune System and Presence in the CNS. 2
Implications of VIP in Neurological Behavior. 4
Hematopoietic Cells Localize in the Central Nervous System. 7
METHODS. 11
Mice. 11
Bone Marrow-Derived Cell Donor Preparation. 11
Preparing the Radiation Chimeras - Hematopoietic Cell Transplantation. 12
Behavioral Testing: pg 12Circadian Rhythms. 13
Forced Swim Test. 13
Contextual Fear Conditioning. 14
Statistical Analysis. 15
RESULTS. 15
Circadian Rhythms: KO Transplants Increase Locomotor Activity. 15
Forced Swim Test: Time Spent Immobile. 17
Contextual Fear Conditioning: Percent Freezing. 18
DISCUSSION. 18
REFERENCES. 24
FIGURES. 32
FIGURE 1. 32
FIGURE 2. 33
FIGURE 3. 34
FIGURE 4. 35
FIGURE 5. 36
FIGURE 6. 37
FIGURE 7. 38
FIGURE 8. 39
FIGURE 9. 40
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