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P2‐415: The 5‐HT 6 receptor antagonist SUVN‐502 enhances acetylcholine and glutamate in rat ventral hippocampus and frontal cortex: A microdialysis study
Author(s) -
Bhyrapuneni Gopinadh,
Muddageswararao,
Benade Vijay,
Saralaya Ramanatha,
Ajjala Devender,
Mudigonda Koteshwara,
Kandikere Vishwottam,
Nirogi Ramakrishna
Publication year - 2008
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2008.05.1494
Subject(s) - microdialysis , glutamate receptor , acetylcholine , hippocampus , neurotransmitter , pharmacology , chemistry , cortex (anatomy) , neuroscience , extracellular , medicine , central nervous system , receptor , biology , biochemistry
Alzheimer’s disease (AD) have evidenced (a) defects in neuronal electrophysiological activity and (b) neuroprotective effects of docosahexaenoic acid (DHA). Methods: To determine how DHA alters the physiology of neurons exposed to amyloid-beta (A eta) and tau pathologies, we examined the effect of DHA dietary intake on intrinsic and synaptic properties using patch-clamp recording of layer III entorhinal cortex neurons of non-transgenic (NonTg) and 3XTg-AD mice. Gas chromatography coupled with flame ionization was performed to determine brain fatty acid profiles. Results: DHA dietary treatment increased DHA (21%, P 0.001) and decreased acid arachidonic (AA) brain content (-24%, P 0.001) in both genotypes. We then found that increased incorporation of DHA into the brain reduced the high discharge frequency (-20%, P 0.01) induced by a depolarizing current injection. Significant relationship between discharge frequency and membrane capacitance (r 0.1043; P 0.001), cortical DHA concentrations (r -0.2140; P 0.05) and AA concentrations (r 0.1861; P 0.05) were detected. Moreover, DHA intake induced a shift in the resting potential of entorhinal cortex neurons from -60mV to -70mV, but only in NonTg mice. Finally, more frequent spontaneous excitatory synaptic events were recorded in cortical neurons of 3XTg-AD mice compared to controls ( 60%, P 0.001), an effect amplified by DHA ( 30% for NonTg and 60% for 3XTg-AD, P 0.001). Interestingly, spontaneous excitatory synaptic events correlated with the increase of DHA brain content (r 0.2627; P 0.01) and the decrease of AA brain content (r -0.2324; P 0.02). Conclusions: These data demonstrate that the functional properties of entorhinal neurons are influenced by accumulation of dietary DHA into the brain and by transgeneinduced Abeta and tau pathologies.