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. 2022 Jan;29(1):7-15.
doi: 10.1177/09727531211059925. Epub 2022 Feb 2.

Cytomorphological Analysis and Interpretation of Nitric Oxide-Mediated Neurotoxicity in Sleep-Deprived Mice Model

Reena Chittora  1   2 , Ayushi Jain  2   3 , Sunil Dutt Shukla  4 , Maheep Bhatnagar  2
Affiliations

Cytomorphological Analysis and Interpretation of Nitric Oxide-Mediated Neurotoxicity in Sleep-Deprived Mice Model

Reena Chittora et al. Ann Neurosci. 2022 Jan.

Abstract

Background: Sleep deprivation (SD) is a biological stress condition for the brain, and the pathogenesis of SD is closely related to elevated oxidative stress, mitochondrial dysfunction, a major cause of neurodegeneration. This oxidative stress-mediated cell death is attributed to rise in calcium ion influx which further excites or alters the neurotransmitters level by activating neuronal nitric oxide (NO) synthase (nNOS) release of NO in mouse SD model. This study indicates that the nitrergic neurons are possible therapeutic targets for the amelioration of SD-induced cognitive dysfunction and behavioral alterations.

Purpose: SD is considered as a risk factor for various neurodegenerative diseases. SD leads to biochemical, behavioral, and neurochemical alterations in animals. This study was designed to explore the possible involvement of a nitrergic neuron system in six days SD-induced morphological and neurodegenerative changes in mice.

Methods: Using nNOS immunohistochemistry, we have investigated the effects of SD on nNOS positive neurons. Immunohistochemical study for the distribution of nNOS positive neuronal cell bodies was carried out in the hippocampus, prefrontal cortex (PFC), and amygdaloid nuclei of mice brain.

Results: Sleep-deprived animals showed a significantly increased number of nNOS positive neurons and altered neuronal cytomorphology as compared with the control group.

Conclusion: These results indicate that total SD may induce morphological changes in nNOS positive neurons in the brain, thus increasing NO synthesis, which is implicated in SD-induced neuronal cell death.

Keywords: Neurodegeneration; Neuronal nitric oxide synthase; Neurotoxicity; Nitric oxide; Sleep deprivation.

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Conflict of interest statement

Declaration of Conflicting Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.. Representative Photomicrographs Showing Immunohistochemical Staining of nNOS Positive Neurons in Different Brain Regions of Control and SD Mice. (1–4): CA1 Subregion of Hippocampus in Control (1, 3) and Sleep-Deprived Mice (2, 4; at 10× and 40× Magnifications). (5–8): CA3 Subregion of Hippocampus in Control (1, 3) and Sleep-Deprived Mice (2, 4; at 10× and 40× Magnifications). (9–12): PFC Region of Brain in Control (13, 15) and Sleep-Deprived Mice (14, 16; at 10× and 40× Magnifications). (17–20): Amygdaloid Nuclei (BMA and Cem) of Brain in Control and Sleep-Deprived Mice (at 10× and 40× Magnifications).
Figure 2.
Figure 2.. Quantitative Analysis of nNOS Positive Neuronal Cells in Different Brain Areas of Mice Brain of Control and Sleep-Deprived Groups.
Figure 3.
Figure 3.. Cell Area of nNOS Positive Neuronal Cells in Different Brain Areas of Mice Brain of Control and Sleep-Deprived Groups.
Figure 4.
Figure 4.. Cell Perimeter of nNOS Positive Neuronal Cells in Different Brain Areas of Mice Brain of Control and Sleep-Deprived Groups.
Figure 5.
Figure 5.. Somatic Aspect Ratio of nNOS Positive Neuronal Cells in Different Brain Areas of Mice Brain of Control and Sleep-Deprived Groups.
Figure 6.
Figure 6.. Somatic Form Factor of nNOS Positive Neuronal Cells in Different Brain Areas of Mice Brain of Control and Sleep-Deprived Groups.
Figure 7.
Figure 7.. Roundness of nNOS Positive Neuronal Cells in Different Brain Areas of Mice Brain of Control and Sleep-Deprived Groups.
Figure 8.
Figure 8.. Compactness of nNOS Positive Neuronal Cells in Different Brain Areas of Mice Brain of Control and Sleep-Deprived Groups.
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