Table 2.
Pharmacological studies of melatonin on different AD models.
| Pharmacological effects | Behavioral or cognitive changes | Mechanisms | Ref. |
|---|---|---|---|
| Amyloid-beta induced AD rats | |||
| Improved spatial learning and memory, synaptic plasticity; reduced astrogliosis and synaptotoxicity | Less time to reach the platform in Morris water maze (MWM) test; more efficient in swimming path | GFAP↓; Musashi1/Notch1/Hes1↑ | 93, 94 |
| Inhibited neurotoxicity and astrocyte activation | NA | GFAP↓; MAP↑; Reelin/Dab1↑ | 78 |
| Improved spatial learning and memory | Shorter latency in MWM test; increase of period in the III quadrant, raise of numbers of line crossings in central square arena in open field test; increase in the latency and decreased errors in step‐through test and step‐down test | GSK-3β, caspase-3, Aβ1-42 , BACE1 and p-tau↓; PP2A and Bcl-2↑; mitochondrial function↑ | 95 |
| Improved memory, hindered anxiety, and attenuated hippocampal cell damage | Increased number of arm entries in Y-maze test; increased number of open arm entries and time spent in open arms in EPM test | SIRT1↑; COX2 and TFAM↑ | 80 |
| Scopolamine induced amnesia mice | |||
| Improved spatial learning and memory | Shorter escape latency in MWM test; longer latency time in passive avoidance test (PAT) | ChAT, CHT and VAChT↑ | 96 |
| Recovered cognitive impairment | Shorter escape latency in MWM test; longer latency time in PAT | MBP, BDNF, and TrkB↑ | 97 |
| Attenuated synaptic dysfunction, memory impairment neuroinflammation | Shorter escape latency in MWM test; increased number of arm entries in Y-maze test | CREB and BDNF ↑; Akt and ERK ↑; GFAP, TNFα and IL6 ↓; JNK, Nrf2 and HO-1 ↓ | 98 |
| Tg2576 mice overexpressed APP | |||
| Ameliorated amygdala-dependent emotional memory | No changes in behavioral tests | PSD95↓; Arc, pCREB and c-Fos↑ | 99 |
| Activated lymphatic system | NA | Aβ↓ | 100, 101 |
| AD transgenic mice | |||
| Induced cognitive enhancement and brain resilience | Novel object recognition (NOR) test | NF-κB, TNFα, IL-1β↓; amyloid and p-tau↓; Gas6 and SIRT1↑ | 85 |
| Improved episodic memory; reduced neuroinflammation; inhibited reactive microgliosis | Less time spent exploring the new object | amyloid aggregates↓ | 102 |
| STZ-induced AD like rats | |||
| Prevented memory impairment; downregulated AD-like hyperphosphorylation | Shorter escape latency in MWM test | MDA↓; SOD and GSH‐Px↑; antioxidation function↑ | 103 |
| Ameliorated memory; prevented brain insulin resistance | Shorter escape latency in MWM test | p-tau, BACE1 and PS1↓; AKT and GSK-3β↑ | 104 |
| Aged mice | |||
| Improved hippocampal neuronal homeostasis | NA | SIRT1, FOXO1, MT1 and MT2↑; p53, ac-p53, MDM2, and DKK1↓ | 105 |