PMID- 29847220 OWN - NLM STAT- MEDLINE DCOM- 20201211 LR - 20201214 IS - 1476-8305 (Electronic) IS - 1028-415X (Linking) VI - 23 IP - 2 DP - 2020 Feb TI - Apigenin reverses behavioural impairments and cognitive decline in kindled mice via CREB-BDNF upregulation in the hippocampus. PG - 118-127 LID - 10.1080/1028415X.2018.1478653 [doi] AB - Objectives: Apigenin is the most common bioflavonoid known to be biologically active after systemic administration and show multiple pharmacological effects. The present study was designed to explore the role of apigenin in pentylenetetrazole (PTZ) kindling associated cognitive and behavioural impairments in the mouse model. Methods: The animals were kindled by injecting a sub-convulsive dose of PTZ (35 mg/kg) on every alternate day, followed by 20 days treatment with apigenin at two different doses (10 and 20 mg/kg). Seizure severity was assessed on every 5th, 10th, 15th, and 20th day during apigenin treatment after a PTZ injection, followed by analysis of cognitive and behavioural functions. Results: Apigenin treatment displayed insignificant effect on seizure severity in kindled mice at both the tested doses, in comparison to control. However, the treatment showed marked increase in per cent spontaneous alterations and decline in the anxiety index in T-maze and elevated plus maze tests, respectively. Apigenin-treated groups showed significant decrease in immobility period in both forced swim and tail suspension tests, without any change in the total locomotor activity in the open field test. Furthermore, increase in the hippocampus protein expression of brain-derived neurotrophic factor (BDNF), cAMP response element binding protein (CREB), and phosphorylated CREB, with increased serotonin level were also observed in the treated animals. Discussion: The results of the present study showed that apigenin treatment prevents cognitive deficit and reverses behaviour impairments, without altering seizures severity in kindled mice. The observed effects can be attributed to CREB-BDNF upregulation in the hippocampus. FAU - Sharma, Pallavi AU - Sharma P AD - Pharmacology and Toxicology Laboratory, CSIR-Institute of Himalayan Bioresource Technology, Palampur, India. AD - Academy of Scientific and Innovative Research (AcSIR), CSIR-Institute of Himalayan Bioresource Technology, Palampur, India. FAU - Sharma, Supriya AU - Sharma S AD - Pharmacology and Toxicology Laboratory, CSIR-Institute of Himalayan Bioresource Technology, Palampur, India. AD - Academy of Scientific and Innovative Research (AcSIR), CSIR-Institute of Himalayan Bioresource Technology, Palampur, India. FAU - Singh, Damanpreet AU - Singh D AD - Pharmacology and Toxicology Laboratory, CSIR-Institute of Himalayan Bioresource Technology, Palampur, India. AD - Academy of Scientific and Innovative Research (AcSIR), CSIR-Institute of Himalayan Bioresource Technology, Palampur, India. LA - eng PT - Journal Article DEP - 20180530 PL - England TA - Nutr Neurosci JT - Nutritional neuroscience JID - 100892202 RN - 0 (Bdnf protein, mouse) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 333DO1RDJY (Serotonin) RN - 7V515PI7F6 (Apigenin) RN - EC 2.3.1.48 (CREB-Binding Protein) RN - EC 2.3.1.48 (Crebbp protein, mouse) RN - WM5Z385K7T (Pentylenetetrazole) SB - IM MH - Animals MH - Anxiety Disorders/prevention & control MH - Apigenin/*administration & dosage MH - Behavior, Animal/drug effects/physiology MH - Brain-Derived Neurotrophic Factor/*analysis MH - CREB-Binding Protein/*analysis MH - Cognitive Dysfunction/chemically induced/*prevention & control MH - Depression/prevention & control MH - Disease Models, Animal MH - Hippocampus/chemistry MH - Kindling, Neurologic/drug effects/*physiology MH - Male MH - Mental Disorders/chemically induced/*prevention & control MH - Mice MH - Pentylenetetrazole/pharmacology MH - Serotonin/analysis MH - Up-Regulation/drug effects OTO - NOTNLM OT - 4',5,7-Trihydroxyflavone OT - Hippocampus OT - Neurotrophic factors OT - Pentylenetetrazol OT - Serotonin OT - Spatial learning OT - cAMP response element binding protein EDAT- 2018/05/31 06:00 MHDA- 2020/12/15 06:00 CRDT- 2018/05/31 06:00 PHST- 2018/05/31 06:00 [pubmed] PHST- 2020/12/15 06:00 [medline] PHST- 2018/05/31 06:00 [entrez] AID - 10.1080/1028415X.2018.1478653 [doi] PST - ppublish SO - Nutr Neurosci. 2020 Feb;23(2):118-127. doi: 10.1080/1028415X.2018.1478653. Epub 2018 May 30.