Central Insulin-like Growth Factor-1 Treatment Enhances Working and Reference Memory by Reducing Neuroinflammation and Amyloid Beta Deposition in a Rat Model of Sporadic Alzheimer’s Disease
Abstract
:1. Introduction
2. Results
2.1. Spatial Memory Impairments in the Morris Water Maze (MWM) Test
2.1.1. Reference Memory in the Morris Water Maze (MWM) Test
2.1.2. Reference Memory Performance in the Probe Test on Day 4 of the Morris Water Maze (MWM) Test
2.1.3. Working Memory During Trials 1–4 of Consecutive Days 5–8 of the Morris Water Maze (MWM) Test
2.2. Microglia Activated Cells (CD68+ Cells) and Amyloid β (Aβ40–42) Deposition in the Hippocampus (CA1, CA2, CA3, DG)
3. Discussion
4. Materials and Methods
4.1. Animals
4.2. Experimental Procedure
4.2.1. Intracerebroventricular (ICV) Co-Injections of Insulin-Like Growth Factor-1 (IGF-1) and Streptozotocin (STZ)
4.2.2. Drug Administration
4.2.3. Behavior Associated with Reference and Working Memory in Morris Water Maze (MWM)
4.2.4. Immunohistochemistry
4.2.5. Quantification of Labeled Cells
4.2.6. Slaughtering Animals and Collection of Tissues
4.2.7. Data Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
IGF-1 | Insulin-like growth factor-1 |
SAL | Saline |
Aβ | Amyloid βeta |
STZ | Streptozotocin |
VEH | Citrate buffer |
AD | Alzheimer’s disease |
sAD | Sporadic Alzheimer’s disease |
CD68+ cells | activated microglia cells |
ICV | Intracerebroventricular |
MWM | Morris Water Maze test |
CA1 CA2 | Cornus ammonis 1 area of the hippocampus Cornus ammonis 2 area of the hippocampus |
CA3 | Cornus ammonis 3 area of the hippocampus |
DG | Dentate gyrus area of the hippocampus |
IL-10 | Interleukin-10 |
IL-4 | Interleukin-4 |
TNF-α | Tumor necrosis factor-α |
IL-1β | Interleukin-1β |
APP | Amyloid precursor protein |
BDNF | Brain-derived neurotrophic factor |
IRS-1 | Insulin receptor substrate 1 |
IRS-2 | Insulin receptor substrate 2 |
cAMP | Cyclic adenosine monophosphate |
PI3K PBS | Phosphoinositide 3-kinase-protein kinase B Phosphate-buffered saline |
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Microglia Cells (CD68+) No./mm2 | |||||
a | Structures/Groups | STZ SAL | STZ IGF-1 | VEH SAL | VEH IGF-1 |
Prefrontal cortex | 0 ± 0 | 0 ± 0 | 0 ± 0 | 0 ± 0 | |
Corpus calosum | 560 ± 151.66 | 475 ± 103.51 | 300 ± 115 | 371.43 ± 131.39 | |
Caudate putamen | 242.86 ± 85.91 $ | 287.5 ± 105.01 $$$^^ | 0 ± 0 | 22.22 ± 11.03 | |
Medial septal nucleus | 142.86 ± 61.00 | 0 ± 0 | 0 ± 0 | 0 ± 0 | |
Lateral preoptic area | 57.14 ± 26.73 $ | 0 ± 0 * | 0 ± 0 | 0 ± 0 | |
Medial preoptic nucleus | 0 ± 0 | 0 ± 0 | 0 ± 0 | 0 ± 0 | |
Supraoptic nucleus | 550 ± 207.36 $$ | 0 ± 0 *** | 0 ± 0 | 37.5 ± 12.93 | |
Arcuate hypothalamic nucleus | 0 ± 0 | 0 ± 0 | 0 ± 0 | 0 ± 0 | |
Dorsomedial hypothalamic nucleus | 42.86 ± 13.37 | 0 ± 0 | 0 ± 0 | 0 ± 0 | |
Lateral hypothalamus | 0 ± 0 | 0 ± 0 | 0 ± 0 | 0 ± 0 | |
Paraventricular hypothalamic nucleus | 114.29 ± 36.60 | 0 ± 0 | 0 ± 0 | 0 ± 0 | |
Ventromedial hypothalamic nucleus | 0 ± 0 | 60 ± 29.44 | 0 ± 0 | 0 ± 0 | |
Nucleus accumbens-Shell | 71.42 ± 37.40 | 0 ± 0 | 0 ± 0 | 0 ± 0 | |
Nucleus accumbens-Core | 57.14 ± 19.67 | 0 ± 0 | 0 ± 0 | 0 ± 0 | |
b | Structures/Groups | VEH SAL | VEH IGF-1 | ||
Hippocampus CA1 | 0 ± 0 | 0 ± 0 | |||
Hippocampus CA2 | 0 ± 0 | 0 ± 0 | |||
Hippocampus CA3 | 0 ± 0 | 0 ± 0 | |||
Dentate gyrus | 0 ± 0 | 0 ± 0 | |||
Amyloid β (40–42)/No./mm2 | |||||
c | Structures/Groups | STZ SAL | STZ IGF-1 | VEH SAL | VEH IGF-1 |
Prefrontal cortex | 3 ± 1.06 $ | 03.06 ± 1.72 | 0 ± 0 | 0 ± 0 | |
Lateral preoptic area | 3 ± 1.13 $$ | 2.65 ± 0.97 $$^^ | 0 ± 0 | 0 ± 0 | |
Medial preoptic nucleus | 5.38 ± 2.36 $$ | 1.99 ± 0.63 $$^^ | 0 ± 0 | 0 ± 0 | |
Nucleus accumbens-Shell | 2.35 ± 1.5 $ | 3.27 ± 1.34 $$^^^ | 0 ± 0 | 0 ± 0 | |
Nucleus accumbens-Core | 2.75 ± 0.86 $$$ | 02.16 ± 0.96 $$^^^ | 0 ± 0 | 0 ± 0 | |
d | Structures/Groups | VEH SAL | VEH IGF-1 | ||
Hippocampus CA1 | 0 ± 0 | 0 ± 0 | |||
Hippocampus CA2 | 0 ± 0 | 0 ± 0 | |||
Hippocampus CA3 | 0 ± 0 | 0 ± 0 | |||
Dentate gyrus | 0 ± 0 | 0 ± 0 |
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Dunacka, J.; Grembecka, B.; Majkutewicz, I.; Wrona, D. Central Insulin-like Growth Factor-1 Treatment Enhances Working and Reference Memory by Reducing Neuroinflammation and Amyloid Beta Deposition in a Rat Model of Sporadic Alzheimer’s Disease. Pharmaceuticals 2025, 18, 527. https://doi.org/10.3390/ph18040527
Dunacka J, Grembecka B, Majkutewicz I, Wrona D. Central Insulin-like Growth Factor-1 Treatment Enhances Working and Reference Memory by Reducing Neuroinflammation and Amyloid Beta Deposition in a Rat Model of Sporadic Alzheimer’s Disease. Pharmaceuticals. 2025; 18(4):527. https://doi.org/10.3390/ph18040527
Chicago/Turabian StyleDunacka, Joanna, Beata Grembecka, Irena Majkutewicz, and Danuta Wrona. 2025. "Central Insulin-like Growth Factor-1 Treatment Enhances Working and Reference Memory by Reducing Neuroinflammation and Amyloid Beta Deposition in a Rat Model of Sporadic Alzheimer’s Disease" Pharmaceuticals 18, no. 4: 527. https://doi.org/10.3390/ph18040527
APA StyleDunacka, J., Grembecka, B., Majkutewicz, I., & Wrona, D. (2025). Central Insulin-like Growth Factor-1 Treatment Enhances Working and Reference Memory by Reducing Neuroinflammation and Amyloid Beta Deposition in a Rat Model of Sporadic Alzheimer’s Disease. Pharmaceuticals, 18(4), 527. https://doi.org/10.3390/ph18040527