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Research article
Momoka Nishimura
Division of Anesthesiology,Department of Surgery Related, Kobe University Graduate School of Medicine
Corresponding Author
ORCiD: https://orcid.org/0000-0001-8882-6998
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Background: There has been much discussion recently about the occurrence of neuropsychological complications during the perioperative period. Diabetes is known to be one of the metabolic risk factors. Although the number of patients with diabetes mellitus (DM) has been increasing, the pathophysiology of postoperative neuropsychological dysfunction in DM patients is still unclear. Recently, a deficiency of neurotransmitters, such as monoamines, was reported to be associated with mental disorders. Therefore, we investigated the effects of surgical stress on behavioral activity and hippocampal noradrenaline (NA) level in type 2 diabetes mellitus model (T2DM) mice. Methods: Eighty-four 6-week-old male C57BL/6J mice were divided into four groups (non-diabetes, non-diabetes with surgery, T2DM, and T2DM with surgery groups). T2DM mice were established by feeding a high-fat diet (HFD) for 8 weeks. At 14 weeks of age, fifteen mice in each group underwent a series of behavioral tests including an open field (OF) test, a novel object recognition (NOR) test and a light-dark (LD) test. In the surgery groups, open abdominal surgery with manipulation of the intestine was performed 24 hours before the behavioral tests as a surgical stress. Hippocampal noradrenaline (NA) concentration was examined in six mice in each group by high-performance liquid chromatography. The data were analyzed by the Mann-Whitney U test, and p values less than 0.05 were considered significant. Results: The T2DM group showed significantly increased explorative activity in the NOR test (P = 0.0016) and significantly increased frequency of transition in the LD test (P = 0.043) compared with those in the non-diabetic group before surgery. In T2DM mice, surgical stress resulted in decreased total distance in the OF test, decreased explorative activity in the NOR test, and decreased frequency of transition in the LD test (OF: P = 0.015, NOR: P = 0.009, LD: P = 0.007) and decreased hippocampal NA (P = 0.015), but such differences were not observed in the non-diabetic mice. Conclusions: Mice with T2DM induced by feeding an HFD showed increased behavioral activities, and surgical stress in T2DM mice caused postoperative hypoactivity and reduction of the hippocampal NA level.
Keywords
Surgical stress; Type 2 diabetes mellitus; Hyperactive behavior; Postoperative hypoactivity
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View the published article at BMC Neuroscience.
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Editorial decision: Accept
On 10 Feb, 2020
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On 09 Feb, 2020
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On 08 Feb, 2020
Editor invited
On 08 Feb, 2020
Version 2
Posted 31 Dec, 2019
No comments provided
Editorial decision: Minor revision
On 30 Jan, 2020
Review #2 received
Received 29 Jan, 2020
Review #1 received
Received 28 Jan, 2020
Reviewer #2 agreed
On 13 Jan, 2020
Reviewer #1 agreed
On 12 Jan, 2020
Reviewers invited
Invitations sent on 08 Jan, 2020
Editor assigned
On 26 Dec, 2019
Submission checks complete
On 25 Dec, 2019
Editor invited
On 25 Dec, 2019
No comments provided
Editorial decision: Minor revision
On 14 Dec, 2019
Review #2 received
Received 19 Nov, 2019
Reviewer #3 agreed
On 10 Nov, 2019
Review #1 received
Received 08 Nov, 2019
Reviewer #1 agreed
On 06 Nov, 2019
Reviewer #2 agreed
On 06 Nov, 2019
Reviewers invited
Invitations sent on 03 Nov, 2019
Submission checks complete
On 28 Oct, 2019
Editor assigned
On 18 Oct, 2019
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On 17 Oct, 2019
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See the published version of this preprint at BMC Neuroscience.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
Momoka Nishimura
Division of Anesthesiology,Department of Surgery Related, Kobe University Graduate School of Medicine
Corresponding Author
ORCiD: https://orcid.org/0000-0001-8882-6998
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at BMC Neuroscience.
No community comments so far
Editorial decision: Accept
On 10 Feb, 2020
Editor assigned
On 09 Feb, 2020
Submission checks complete
On 08 Feb, 2020
Editor invited
On 08 Feb, 2020
Version 2
Posted 31 Dec, 2019
No comments provided
Editorial decision: Minor revision
On 30 Jan, 2020
Review #2 received
Received 29 Jan, 2020
Review #1 received
Received 28 Jan, 2020
Reviewer #2 agreed
On 13 Jan, 2020
Reviewer #1 agreed
On 12 Jan, 2020
Reviewers invited
Invitations sent on 08 Jan, 2020
Editor assigned
On 26 Dec, 2019
Submission checks complete
On 25 Dec, 2019
Editor invited
On 25 Dec, 2019
No comments provided
Editorial decision: Minor revision
On 14 Dec, 2019
Review #2 received
Received 19 Nov, 2019
Reviewer #3 agreed
On 10 Nov, 2019
Review #1 received
Received 08 Nov, 2019
Reviewer #1 agreed
On 06 Nov, 2019
Reviewer #2 agreed
On 06 Nov, 2019
Reviewers invited
Invitations sent on 03 Nov, 2019
Submission checks complete
On 28 Oct, 2019
Editor assigned
On 18 Oct, 2019
First submitted
On 17 Oct, 2019
Editor invited
On 17 Oct, 2019
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at BMC Neuroscience.
Background: There has been much discussion recently about the occurrence of neuropsychological complications during the perioperative period. Diabetes is known to be one of the metabolic risk factors. Although the number of patients with diabetes mellitus (DM) has been increasing, the pathophysiology of postoperative neuropsychological dysfunction in DM patients is still unclear. Recently, a deficiency of neurotransmitters, such as monoamines, was reported to be associated with mental disorders. Therefore, we investigated the effects of surgical stress on behavioral activity and hippocampal noradrenaline (NA) level in type 2 diabetes mellitus model (T2DM) mice. Methods: Eighty-four 6-week-old male C57BL/6J mice were divided into four groups (non-diabetes, non-diabetes with surgery, T2DM, and T2DM with surgery groups). T2DM mice were established by feeding a high-fat diet (HFD) for 8 weeks. At 14 weeks of age, fifteen mice in each group underwent a series of behavioral tests including an open field (OF) test, a novel object recognition (NOR) test and a light-dark (LD) test. In the surgery groups, open abdominal surgery with manipulation of the intestine was performed 24 hours before the behavioral tests as a surgical stress. Hippocampal noradrenaline (NA) concentration was examined in six mice in each group by high-performance liquid chromatography. The data were analyzed by the Mann-Whitney U test, and p values less than 0.05 were considered significant. Results: The T2DM group showed significantly increased explorative activity in the NOR test (P = 0.0016) and significantly increased frequency of transition in the LD test (P = 0.043) compared with those in the non-diabetic group before surgery. In T2DM mice, surgical stress resulted in decreased total distance in the OF test, decreased explorative activity in the NOR test, and decreased frequency of transition in the LD test (OF: P = 0.015, NOR: P = 0.009, LD: P = 0.007) and decreased hippocampal NA (P = 0.015), but such differences were not observed in the non-diabetic mice. Conclusions: Mice with T2DM induced by feeding an HFD showed increased behavioral activities, and surgical stress in T2DM mice caused postoperative hypoactivity and reduction of the hippocampal NA level.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
This is a list of supplementary files associated with this preprint. Click to download.
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