Table 3.

In vivo studies related to the neuroprotective effects of melatonin in AD. Abbreviations: AChE, Acetylcholinesterase; APP, Amyloid-beta precursor protein; Aβ, Amyloid-beta, AβO, Amyloid-beta oligomers; BDNF, Brain-derived neurotrophic factor; ChAT, Choline acetyltransferase; CREB, cAMP Response Element-Binding Protein; LPS, Lipopolysaccharides; SD, Sprague Dawley.

Animal Model	Gender	Age	Treatment Dosage and Duration	AD Pathology Involved	Effects on AD Pathology	Effects on Neurotransmission	References
Tg2576 mice	N/A	8, 9.5, 11, 12.5 months old	0.5 mg/mL, 4, 5.5, 7, 8.5 months	Plaque-like deposits of amyloid-beta	Reduced time-dependent Aβ levels, abnormal nitration on proteins Increased mice survival	N/A	[72]
ICR mice treated with Aβ1-42	Male	N/A	10 mg/kg, 5 mg/kg, 2.5 mg/kg, 14 days	Affected cognitive functions	Improved cognitive deficits and spontaneous activity of mice Reduced hyperphosphorylated tau expression	Improved neuron viability	[79]
AβPP/PS mice	N/A	4 months old	100 µg/mL,0.5 mg/day	Amyloid plaques, behavioral deficits	Melatonin improved spatial learning and memory Aβ load in hippocampus and frontal cortex were reduced	N/A	[44]
APP/PS1 mice	N/A	2–2.5 months old	100 mg/L	Aβ plaques	Reduced Aβ plaques deposition in hippocampus and entorhinal cortex Decreased inflammatory cytokines in hippocampus	N/A	[71]
3xTg-AD mice	Male	6 months old	10 mg/kg body weight	AβO, hyper-phosphorylated tau	Decreased number of Aβ oligomers and hyperphosphorylated tau Protection from cognitive impairment, brain oxidative stress, decrease in mitochondrial DNA	N/A	[78]
SD rats treated with LPS	N/A	N/A	5 and 10 mg/kg	Inflammation, oxidation, increased AChE activity	Lowered levels of induced inflammation and oxidation	Inhibited increase in AchE activity	[13]
APP695 mice	N/A	4 months old	10 mg/kg/day	Aβ plaques, decreased ChAT levels	Long-term treatment significantly reduced Aβ plaque levels	Increased ChAT activity in frontal cortex and hippocampus	[81]
Swiss mice treated with AlCl3 and d-galactose	Male	N/A	80 mg/kg/day	Affected cognitive functions, decreased BDNF, CREB and AChE levels	Increased BDNF and CREB levels Improved memory deficits	Increased AChE level	[82]