PMID- 28861754 OWN - NLM STAT- MEDLINE DCOM- 20180802 LR - 20181113 IS - 1573-6903 (Electronic) IS - 0364-3190 (Linking) VI - 42 IP - 12 DP - 2017 Dec TI - Estrogen Receptor beta Mediated Neuroprotective Efficacy of Cicer microphyllum Seed Extract in Global Hypoxia. PG - 3474-3489 LID - 10.1007/s11064-017-2395-5 [doi] AB - Hypoxia induced oxidative stress and neurodegeneration in the hippocampus has been implicated for memory impairment in conditions like stroke, ischemia and hypobaric hypoxia. The present study, aimed at investigating the potential of ethanolic extract of Cicer microphyllum seeds (CSE) for amelioration of global hypoxia induced neurodegeneration in CA1 region of hippocampus. CSE supplementation considerably reduced neurodegeneration and dendritic atrophy in CA1 neurons along with improvement of memory in hypoxic rats. This effect of CSE was partly attributed to its antioxidant activity resulting in reduction of lipid peroxidation, protein oxidation and DNA damage during exposure to chronic hypoxia. CSE also promoted dendritic arborization through activation of estrogen receptor beta (ERbeta) and phosphorylation of extracellular signal regulated kinase (ERK1/2) which was independent of brain derived neurotrophic factor (BDNF) mediated signalling mechanisms. Extra nuclear activation of ERK1/2 by ERbeta resulted in phosphorylation of cyclic AMP response element binding protein (CREB) leading to increased expression of PSD-95.These molecular alterations translated to behavioural changes in CSE administered hypoxic animals that performed better in Morris Water Maze Task as compared to vehicle treated hypoxic animals. Toxicological studies show NOEAL > 2000 mg/kg b.w. for oral administration of CSE indicating its safety for consumption. Our findings not only suggest the neuroprotective potential of CSE in hypoxia but also provide evidence for involvement of estrogen receptor and pCREB mediated nootropic effect of the extract. FAU - Sharma, Deepti AU - Sharma D AD - Defence Institute of High Altitude Research, Defence Research and Development Organisation, C/o 56 APO, Ladakh, Leh, Jammu And Kashmir, 901205, India. FAU - Biswal, Surya Narayan AU - Biswal SN AD - Defence Institute of High Altitude Research, Defence Research and Development Organisation, C/o 56 APO, Ladakh, Leh, Jammu And Kashmir, 901205, India. FAU - Kumar, Kushal AU - Kumar K AD - Defence Institute of High Altitude Research, Defence Research and Development Organisation, C/o 56 APO, Ladakh, Leh, Jammu And Kashmir, 901205, India. FAU - Bhardwaj, Pushpendar AU - Bhardwaj P AD - Defence Institute of High Altitude Research, Defence Research and Development Organisation, C/o 56 APO, Ladakh, Leh, Jammu And Kashmir, 901205, India. FAU - Barhwal, Kalpana Kumari AU - Barhwal KK AD - All India Institute of Medical Sciences, Sijua, Bhubaneswar, Odisha, 751019, India. FAU - Kumar, Ashish AU - Kumar A AD - Defence Institute of High Altitude Research, Defence Research and Development Organisation, C/o 56 APO, Ladakh, Leh, Jammu And Kashmir, 901205, India. FAU - Hota, Sunil Kumar AU - Hota SK AD - Defence Institute of High Altitude Research, Defence Research and Development Organisation, C/o 56 APO, Ladakh, Leh, Jammu And Kashmir, 901205, India. drsunilhota@hotmail.com. FAU - Chaurasia, Om Prakash AU - Chaurasia OP AD - Defence Institute of High Altitude Research, Defence Research and Development Organisation, C/o 56 APO, Ladakh, Leh, Jammu And Kashmir, 901205, India. LA - eng PT - Journal Article DEP - 20170831 PL - United States TA - Neurochem Res JT - Neurochemical research JID - 7613461 RN - 0 (Estrogen Receptor beta) RN - 0 (Nootropic Agents) RN - 0 (Reactive Oxygen Species) SB - IM MH - Animals MH - *Cicer MH - Estrogen Receptor beta/*metabolism MH - Hippocampus/*metabolism MH - Hypoxia/*metabolism MH - Male MH - Maze Learning/drug effects MH - Memory/drug effects/physiology MH - Memory Disorders/metabolism MH - Neurons/drug effects/metabolism MH - Neuroprotection/drug effects MH - Nootropic Agents/pharmacology MH - Oxidative Stress/drug effects MH - Rats, Sprague-Dawley MH - Reactive Oxygen Species/metabolism MH - Seeds OTO - NOTNLM OT - Cicer microphyllum seed extract OT - Dendritic arborization OT - Estrogen receptorbeta OT - Hypoxia OT - Memory OT - Phytoestrogen EDAT- 2017/09/02 06:00 MHDA- 2018/08/03 06:00 CRDT- 2017/09/02 06:00 PHST- 2017/03/21 00:00 [received] PHST- 2017/08/23 00:00 [accepted] PHST- 2017/08/17 00:00 [revised] PHST- 2017/09/02 06:00 [pubmed] PHST- 2018/08/03 06:00 [medline] PHST- 2017/09/02 06:00 [entrez] AID - 10.1007/s11064-017-2395-5 [pii] AID - 10.1007/s11064-017-2395-5 [doi] PST - ppublish SO - Neurochem Res. 2017 Dec;42(12):3474-3489. doi: 10.1007/s11064-017-2395-5. Epub 2017 Aug 31.