Data for: Protective effects of melatonin against valproic acid-induced memory impairments and reductions in adult rat hippocampal neurogenesis

Published: 26-04-2021| Version 1 | DOI: 10.17632/2bp39kjmgv.1
Jariya Welbat


Valproic acid (VPA) is widely used in the treatment of epilepsy. However, VPA has been revealed to impair memory in both humans and animals. The adverse effects of VPA are associated with reductions in hippocampal neurogenesis and memory. There are neuroprotective properties exerted by melatonin. As such, the present study investigated the protective effects of melatonin against the reductions of memory and neurogenesis caused by VPA. Male Spraque-Dawley rats received VPA (300 mg/kg) twice a day for 14 days, or melatonin (8 mg/kg/day) for 14 days, or co-treatment with VPA and melatonin for either 14 days (preventive and recovery groups) or 28 days (throughout group). Novel object location (NOL) and novel object recognition (NOR) tests were used to assess spatial memory and non-spatial memory, respectively. Proliferation, survival, and immature neurons in the subgranular zone (SGZ) were examined using Ki-67, BrdU and doublecortin (DCX) immunohistochemistry. Exploration time was scored when animals directed theirs nose toward the objects at a distance less than 2 cm. All sections were quantified at X40 on a Nikon ECLIPSE 80i fluorescence microscope. Ki-67, BrdU and DCX positive cells were considered within the SGZ, which is defined as 3 cell breadths of the internal rim of both blades of the dentate gyrus. The numbers of Ki-67, BrdU, and DCX positive cells in each section were calculated by accumulating cell counts per section for 9 sections per brain and multiplying the results by 15 for Ki67 and 8 for BrdU and DCX. The Student’s t-test and one-way ANOVA were used to analyse data where appropriate. Exploration times from both tests were calculated and converted to a preference index (PI), defined as time spent exploring for novelty in the choice trial as a percentage in comparison to 50% chance. The exploration time of either object placed in the novel location or novel object was significant greater than familiar location or object, demonstrating that the animals had normal cognition. If the PI is significant higher than 50% chance, suggesting that the animals did not have memory deficits. For immunostaining, the number of Ki-67, BrdU and DCX positive cells in control group was compared with valproic acid, melatonin, preventive, recovery, and throughout groups to show changes of neurogenesis.