Effect of cholecystokinin on learning and memory, neuronal proliferation and apoptosis in the rat hippocampus

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Abstract

Background:

Cholecystokinin (CCK) has roles in learning and memory, but the cellular mechanism is poorly understood. This study investigated the effect of CCK on spatial learning and memory, neuronal proliferation and apoptosis in the hippocampus in rats.

Materials and Methods:

Experimental groups were control and CCK. The rats received CKK octapeptide sulfated (CCK-8S, 1.6 μg/kg, i.p.) for 14 days. Spatial learning and memory were tested by Morris water maze and finally immunohistochemical study was performed; neurogenesis by Ki-67 method and apoptosis by Terminal deoxynucleotidyl transferase mediated dUTP Nick End Labeling (TUNEL) assay in hippocampal dentate gyrus (DG).

Results:

Cholecystokinin increased Ki-67 positive cells and reduced TUNEL positive cells in the granular layer of hippocampal DG. CCK failed to have a significant effect on spatial learning and memory.

Conclusion:

Results indicate neuroprotective and proliferative effects of CCK in the hippocampus; however, other factors are probably involved until the newly born neurons achieve necessary integrity for behavioral changes.

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Most cited references 21

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An autoradiographic study of the time of origin and the pattern of granule cell migration in the dentate gyrus of the rat.

D Gottlieb, A Schlessinger, Frances M. Cowan (1975)

The dentate gyrus of the rat contains about 600,000 granule cells. These small neurons are generated over a prolonged period from the 14th day of gestation until some time after the second postnatal week. The majority of the cells pass through their last phase of DNA synthesis in the postnatal period, and during the peak period of cell generation, between the fifth and seventh days after birth, up to 50,000 granule cells are formed each day. Contrary to earlier reports, most of the cells pass through their last mitotic division either within the stratum granulosum itself, or within the hilar region of the developing gyrus. The precursor population of cells in the hilar region must therefore constitute a pool of true neuroblasts. The origin of this pool of cells has not been definitely established but it seems probable that its cells are derived from the neuroepithelium lining the lateral ventricle adjacent to the region from which the hippocampal pyramidal cells are generated. Examination of the final location of granule cells labeled at different stages reveals three distinct morphogenetic gradients in the gyrus. The cells in the dorsal blade tend to be formed earlier than those in the ventral blade; cells in the more caudal (or temporal) portions of the gyrus are generated earlier than those in more rostral (or septal) regions; and in all regions the more superficial neurons in the stratum granulosum are formed earlier than the deeper granule cells. The bearing of some of these findings on the development and organization of the connections of the dentate gyrus is discussed.

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Adult-generated hippocampal and neocortical neurons in macaques have a transient existence.

N Vail, Kenneth Gould, M Wagers … (2001)

Previously we reported that new neurons are added to the hippocampus and neocortex of adult macaque monkeys. Here we compare the production and survival of adult-generated neurons and glia in the dentate gyrus, prefrontal cortex, and inferior temporal cortex. Twelve adult macaques were injected with the thymidine analogue BrdUrd, and the phenotypes of labeled cells were examined after 2 h, 24 h, 2 wk, 5 wk, 9 wk, and 12 wk by using the following immunocytochemical markers: for immature and mature neurons, class III beta-tubulin (TuJ1); for mature neurons, neuronal nuclei; for astrocytes, glial fibrillary acidic protein; and for oligodendrocytes, 2',3'-cyclic nucleotide 3' phosphodiesterase. We found that the dentate gyrus had many more BrdUrd-labeled cells than either neocortical area. Furthermore, a greater percentage of BrdUrd-labeled cells expressed a neuronal marker in the dentate gyrus than in either neocortical area. The number of new cells in all three areas declined by 9 wk after BrdUrd labeling, suggesting that some of the new cells have a transient existence. BrdUrd-labeled cells also were found in the subventricular zone and in the white matter between the lateral ventricle and neocortex; some of the latter cells were double-labeled for BrdUrd and TuJ1. Adult neocortical neurogenesis is not restricted to primates. Five adult rats were injected with BrdUrd, and after a 3-wk survival time, there were cells double-labeled for BrdUrd and either TuJ1 or neuronal nuclei in the anterior neocortex as well as the dentate gyrus.

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Erythropoietin improves neuronal proliferation in dentate gyrus of hippocampal formation in an animal model of Alzheimer's disease

Zohreh Arabpoor, Gholamali Hamidi, Bahman Rashidi … (2012)

Background: Alzheimer's disease (AD) is a prevalent disorder with severe learning and memory defects. Because it has been demonstrated that erythropoietin (EPO) has positive effects on the central nervous system, the aim of this study was to evaluate the effect of EPO on neuronal proliferation in dentate gyrus of hippocampal formation in a well-defined model for AD. Materials and Methods: A rat model of sporadic dementia of Alzheimer's type was established by a bilateral intracerebroventricular injection of streptozotocin (ICV-STZ). Impairment of learning and memory was confirmed 2 weeks after ICV-STZ injection by passive avoidance learning test and then rats were divided into fourgroups:Control, control-EPO, Alzheimer and Alzheimer-EPO. EPO was injected intraperitoneally every other day with a dose of 5000 IU/kg and, finally, the rats were anesthetized and decapitated for immunohistochemical study and neurogenesis investigation (by Ki67 method) in dentate gyrus of hippocampal formation. Results: The results driven from the histological study showed that EPO significantly increases neuronal proliferation in dentate gyrus of hippocampus in the Alzheimer-EPO group compared with the control, control-EPO and Alzheimer groups; however, there were no differences between the other groups. Conclusion: Our results show that even though EPO in intact animals doesnot change neurogenesis in dentate gyrus, it can nonetheless significantly increase neurogenesis if there is an underlying disorder like neurodegenerative diseases.

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Author and article information

Journal

Journal ID (nlm-ta): Adv Biomed Res

Journal ID (iso-abbrev): Adv Biomed Res

Journal ID (publisher-id): ABR

Title: Advanced Biomedical Research

Publisher: Medknow Publications & Media Pvt Ltd (India )

ISSN (Electronic): 2277-9175

Publication date Collection: 2015

Publication date (Electronic): 07 October 2015

Volume: 4

Electronic Location Identifier: 227

Affiliations

[1 ]Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

[2 ]Biosensor Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

[3 ]Physiology Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

[4 ]School of Dentistry, Isfahan University of Medical Sciences, Isfahan, Iran

[5 ]Department of Anatomical Sciences, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

Author notes

Address for correspondence: Dr. Bahman Rashidi, Department of Anatomical Sciences, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran. E-mail: b_rashidi@ 123456med.mui.ac.ir

Article

Publisher ID: ABR-4-227

DOI: 10.4103/2277-9175.166650

PMC ID: 4638054

SO-VID: c600e1ff-af92-43c6-a9a8-5fa62b4f5d4a

License:

This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

Effect of cholecystokinin on learning and memory, neuronal proliferation and apoptosis in the rat hippocampus

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Abstract

Background:

Materials and Methods:

Results:

Conclusion:

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Most cited references 21

An autoradiographic study of the time of origin and the pattern of granule cell migration in the dentate gyrus of the rat.

Adult-generated hippocampal and neocortical neurons in macaques have a transient existence.

Erythropoietin improves neuronal proliferation in dentate gyrus of hippocampal formation in an animal model of Alzheimer's disease

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