Progress in neuro-psychopharmacology & biological psychiatry

All-trans retinoic acid rescues memory deficits and neuropathological changes in mouse model of streptozotocin-induced dementia of Alzheimer's type.

PMID 23044340


Recent studies have revealed that aberrant vitamin A signaling may lead to memory deficits in rodents. Present study investigates the potential of all-trans-retinoic acid (ATRA) an agonist at retinoid acid family of receptors, in cognitive dysfunctions associated with experimental dementia. Streptozotocin (STZ) [3 mg/kg, intracerebroventricularly (i.c.v)] was administered on alternate days (day 1 and day 3) to induce dementia in Swiss albino mice. STZ mice were administered ATRA (10 mg/kg; 20 mg/kg, p.o.) for a total of 19 days following second i.c.v injection of STZ [day 4 to day 22]. Morris water maze (MWM) test was performed on days 19, 20, 21, 22 and 23 to assess learning and memory of the animals. Following MWM test, the animals were sacrificed for biochemical and histopathological studies. Extent of oxidative stress was measured by estimating the levels of brain reduced glutathione (GSH) and thiobarbituric acid reactive species (TBARS). Brain acetylcholinestrase (AChE) activity and serum cholesterol levels were also estimated. The brain level of myeloperoxidase (MPO) was measured as a marker of inflammation. STZ produced a marked decline in MWM performance of the animals, reflecting impairment of learning and memory. STZ treated mice showed marked accentuation of AChE activity, TBARS and MPO levels along with fall in GSH level. Further the stained micrographs of STZ-treated mice indicated pathological changes, severe neutrophilic infiltration and amyloid deposition. ATRA treatment significantly attenuated STZ-induced memory deficits, biochemical and histopathological alterations. The findings demonstrate that the memory restorative ability of ATRA may be attributed to its anti-cholinesterase, anti-oxidative and anti-inflammatory potential.