Table 2.

Applications of metformin in animal models of neurological diseases.

Neurological Condition	Model	Metformin Administration	Results	References
Alzheimer’s disease (AD)	3× Tg-AD mice (male, female)	200 mg/kg by intraperitoneal injection (14 days) in drinking water (4 mg/mL) starting at the age of 7–8 months for a period of 6 weeks.	Metformin restored neurogenesis and spatial memory deficits of AD in mice.	[85]
Parkinson’s disease (PD)	N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)/p-induced PD mouse model (male, 16–18 weeks)	100 mg/kg (2 weeks) dissolved in drinking water.	Metformin delayed astrocyte senescence and prevented neurodegeneration.	[86]
Temporal lobe epilepsy (TLE)	Wistar rats (male, 180–200 g)	200 mg/kg by oral gavage.	Metformin improved TLE associated cognitive impairment by inhibiting neuroinflammation and neurodegeneration. Metformin inhibited TLE-associated microglial and astroglial activation.	[87]
Huntington’s disease (HD)	Caenorhabditis elegans	150 or 2000 μM in E. coli strain OP50 food source.	Metformin reduced polyglutamine-induced toxicity.	[88]
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD)	C9orf72 ALS/FTD BAC mice	5 mg/mL metformin in the drinking water (for 3 months starting at 2 months of age, and for 4 months starting at 6 months of age).	Metformin improves ALS/FTD phenotypes.	[89]
Multiple sclerosis (MS)	C57/BL6 mice	250 mg/kg or 500 mg/kg in drinking water (female, for 2.5 weeks starting at 8 weeks of age).	Metformin increases oligodendrocyte AMPK activation and oligodendrocyte differentiation.	[90]
Fragile X syndrome (FXR)	Fmr1−/y mice	200 mg/kg bodyweight/day intraperitoneal injection (males, 10 days).	Metformin rescues phenotypes and normalizes ERK signaling, eIF4E phosphorylation and MMP-9 expression.	[91]