N-Acetylcysteine Amide against Aβ-Induced Alzheimer’s-like Pathology in Rats
Abstract
:1. Introduction
2. Results
2.1. Assessment of Spatial Learning and Memory
2.1.1. Morris Water Maze—Learning
2.1.2. Morris Water Maze—Memory Retention
2.2. Assessment of Passive Avoidance Learning and Memory Using Passive Avoidance Test
2.2.1. Passive Avoidance—Learning
2.2.2. Passive Avoidance—Memory Retention
2.3. Results of the Biochemical and Morphological Studies
2.3.1. Doublecortin Protein Expression in the Hippocampus (Neurogenesis)
2.3.2. Doublecortin Immunostaining
2.4. Synaptophysin Protein Expression in the Hippocampus and Prefrontal Cortex
2.4.1. Synaptophysin Protein Level in the Hippocampus
2.4.2. Synaptophysin Immunostaining in the Hippocampus
2.4.3. Synaptophysin Protein Estimation in the Medial Prefrontal Cortex
2.4.4. Synaptophysin Immunostaining in the Prefrontal Cortex
2.5. Aβ Protein Expression in the Hippocampus and Medial Prefrontal Cortex
2.5.1. Aβ Protein Level in the Hippocampus
2.5.2. Aβ Immunostaining of the Hippocampus
2.5.3. Aβ Protein Level in the Medial Prefrontal Cortex
2.5.4. Aβ Immunostaining of the Medial Prefrontal Cortex
2.6. Tau immunostaining of the Hippocampus and Medial Prefrontal Cortex
2.6.1. Tau Immunostaining of the Hippocampus
2.6.2. Tau Immunostaining of the Medial Prefrontal Cortex
2.7. Cresyl Violet Staining and NeuN Immunostaining
2.7.1. Cresyl Violet Staining and NeuN Immunostaining of the Hippocampus
2.7.2. Cresyl Violet Staining and NeuN Immunostaining of the Medial Prefrontal Cortex
2.8. GFAP and Iba1Immunostaining of the Hippocampus
2.8.1. GFAP Immunostaining of the Hippocampus
2.8.2. Iba1 Immunostaining of the Hippocampus
2.8.3. GFAP Immunostaining of the Medial Prefrontal Cortex
2.8.4. Iba1 Immunostaining of the Medial Prefrontal Cortex
2.9. Oxidants and Antioxidant Levels
2.9.1. MDA Level in the Hippocampus
2.9.2. MDA Level in The medial Prefrontal Cortex
2.9.3. Reduced GSH Level in the Hippocampus
2.9.4. Reduced GSH Level in the Medial Prefrontal Cortex
2.9.5. Total Antioxidants Level in the Hippocampus
2.9.6. Total Antioxidants Level in the Medial Prefrontal Cortex
3. Discussion
3.1. NACA Reversed Oxidative Stress-Induced Cognitive Dysfunction
3.2. NACA Downregulated Oxidative Stress-Induced Aβ Pathology
3.3. NACA Reversed Oxidative Stress-Induced Tau and NFT Expression
3.4. NACA Ameliorated Oxidative Stress-Induced Downregulation of Synaptophysin
3.5. NACA Reversed Oxidative Stress-Induced Reduced Neurogenesis
3.6. NACA Reversed Oxidative Stress-Induced Gliosis
3.7. NACA Ameliorated Oxidative Stress-Induced Neuronal Loss
4. Materials and Methods
4.1. Animals and Ethics Approval
4.2. Animal Groups and Experimental Design
- i.
- Normal control (NC) group: The rats in the normal control group were undisturbed in their home cages except for daily intraperitoneal (ip) injection of normal saline (0.5 mL) during the experimental period (seven consecutive days).
- ii.
- Sham (SH) group: The rats in the sham group underwent sham stereotaxic surgery as described below and 5 µL of sterile saline was infused into each lateral ventricle (bilateral icv (intracerebroventricular) infusion) via a 10 µL Hamilton micro-syringe. Throughout the study period, these rats remained in their home cages and received daily intraperitoneal injections of normal saline (0.5 mL), as with those rats in the NC group.
- iii.
- Amyloid-β (Aβ) group: The rats in this group underwent stereotaxic surgery as described below and 5 µL of sterile Aβ1-42 peptide solution (5 µg Aβ1-42/5 µL sterile saline) was infused into each lateral ventricle. The rats in this group remained in their home cages and received daily ip injections of normal saline (0.5 mL) for seven consecutive days.
- iv.
- Amyloid-β + N-Acetyl Cysteine Amide (Aβ + N) group: The rats in this group were infused with 5 µL of Aβ1-42 peptide solution (5 µg Aβ1-42/5µL sterile saline) into each lateral ventricle as in the Aβ group above. However, from the day of Aβ1-42 peptide infusion, these rats received N-Acetyl Cysteine Amide (NACA), 75 mg/kg/day (ip) for seven consecutive days.
- v.
- N-Acetyl Cysteine Amide + Amyloid-β + N-Acetyl Cysteine Amide (N + Aβ + N) group: The rats in this group were treated with NACA (75 mg/kg/day, ip) for seven consecutive days. This was followed by infusion of 5 µL of Aβ1-42 peptide (5 µg Aβ1-42/5 µL sterile saline) into each lateral ventricle. The NACA treatment (75 mg/kg/day, ip) was then continued further for seven more days (n = 18/group).(Supplementary Figure S9).
4.3. Stereotaxic Surgery and Intracerebroventricular Infusion of Aβ1-42 Peptide or Normal Saline
4.4. NACA Administration
4.5. Morris Water Maze Test
4.6. Passive Avoidance Test
4.7. Tissue Fixation and Processing for Section Cutting
4.8. Cresyl Violet Staining
4.9. Immunostaining (DCX, SYN, Aβ, Tau, NeuN, GFAP and Iba1)
4.10. Western Blotting for DCX, Aβ and SYN
4.11. Analysis of Oxidant/Antioxidants in Hippocampal and Medial Prefrontal Cortex Tissue ELISA Method
4.11.1. Estimation of Malondialdehyde (MDA)
4.11.2. Estimation of Reduced GSH
4.11.3. Estimation of Total Antioxidants
4.11.4. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Alkandari, A.F.; Madhyastha, S.; Rao, M.S. N-Acetylcysteine Amide against Aβ-Induced Alzheimer’s-like Pathology in Rats. Int. J. Mol. Sci. 2023, 24, 12733. https://doi.org/10.3390/ijms241612733
Alkandari AF, Madhyastha S, Rao MS. N-Acetylcysteine Amide against Aβ-Induced Alzheimer’s-like Pathology in Rats. International Journal of Molecular Sciences. 2023; 24(16):12733. https://doi.org/10.3390/ijms241612733
Chicago/Turabian StyleAlkandari, Ahmed Fareed, Sampath Madhyastha, and Muddanna S. Rao. 2023. "N-Acetylcysteine Amide against Aβ-Induced Alzheimer’s-like Pathology in Rats" International Journal of Molecular Sciences 24, no. 16: 12733. https://doi.org/10.3390/ijms241612733
APA StyleAlkandari, A. F., Madhyastha, S., & Rao, M. S. (2023). N-Acetylcysteine Amide against Aβ-Induced Alzheimer’s-like Pathology in Rats. International Journal of Molecular Sciences, 24(16), 12733. https://doi.org/10.3390/ijms241612733