Effects of DHEA administration on learning memory, PKC activity, membrane fluidity and CREB levels in iron-induced epileptic model
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Jawaharlal Nehru University, School of Life Sciences, India
Introduction: Iron-induced post-traumatic epilepsy model reproduces the human post-traumatic condition. Which help to study the preclinical screening of antiepileptic drugs, antioxidant compounds, natural products etc. Oxidative stress has been widely demonstrated that iron-induced epilepsy involves free radical generation and influences lipids and proteins. DHEA is a known neurosteroid, possesses antioxidant properties, it has been shown to be neuroprotective against oxidative stress in rat hippocampal culture. The levels of DHEA are found to be decline during aging, certain types of illness and stress. Therefore a decrease in DHEA levels may contribute significantly to the increased vulnerability of the aged or stressed human brain to dysfunction, disorder or diseases. Therefore, in the present study, we studied the effect of learning memory, Protein Kinase C (PKC), membrane fluidity and CREB levels in epileptic rats.
Material and methods: Twenty five wistar rats of 8-10 months of age were used for this study. Intracortical injection of FeCl3 (100 mM, 5µl, 5 minutes) was used to induce epileptogenesis. Intraperitonial injection of DHEA (30 mg/kg bw/day) was administered for 7,14 and 21 days. Learning memory test was done by morris water maze and anxiety levels were tested by open field test. PKC activity and membrane fluidity was measured in synaptosomal fraction. mRNA levels of CREB was done by RT-PCR.
Results: In epileptic rats loss of memory, increased levels of PKC, decreased membrane fluidity and upregulation of CREB was observed. DHEA administration improves learning and memory in iron-induced epileptic rats. DHEA treatment of epileptic rats resulted in decreased PKC activity and restored membrane fluidity to normal. DHEA treatment of iron-induced epileptic rats resulted in decreased mRNA levels of CREB.
Discussion and conclusion: Our study demonstrated that DHEA suppresses iron-induced experimental seizure activity, and counter epileptogenesis-related cognitive deficits. The results demonstrate that DHEA could be an antiseizure compound to be used clinically to inhibit the vulnerability and severity of post-traumatic seizures in patients suffering from trauma or head injury. Mechanism by which DHEA may act in seizure processes needs consideration.
Keywords:
Membrane Fluidity,
CREB,
DHEA,
Learning memory,
PKC activity
Conference:
XII International Conference on Cognitive Neuroscience (ICON-XII), Brisbane, Queensland, Australia, 27 Jul - 31 Jul, 2014.
Presentation Type:
Poster
Topic:
Memory and Learning
Citation:
Mishra
M and
Sharma
D
(2015). Effects of DHEA administration on learning memory, PKC activity, membrane fluidity and CREB levels in iron-induced epileptic model.
Conference Abstract:
XII International Conference on Cognitive Neuroscience (ICON-XII).
doi: 10.3389/conf.fnhum.2015.217.00223
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Received:
19 Feb 2015;
Published Online:
24 Apr 2015.
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Correspondence:
Prof. Deepak Sharma, Jawaharlal Nehru University, School of Life Sciences, New Delhi, India, deepak57in@yahoo.co.in