Abstract:
:Abuse of alcohol triggers neurodegeneration in human brain. Minocycline has characteristics conferring neuroprotection. Current study evaluates the role of the CREB-BDNF signaling pathway in mediating minocycline's neuroprotective effects against alcohol-induced neurodegeneration. Seventy adult male rats were randomly split into groups 1 and 2 that received saline and alcohol (2 g/kg/day by gavage, once daily), respectively, and groups 3, 4, 5, and 6 were treated simultaneously with alcohol and minocycline (10, 20, 30 and 40 mg/kg I.P, respectively) for 21 days. Group 7 received minocycline alone (40 mg/kg, i.p) for 21 days. Morris water maze (MWM) has been used to assess cognitive activity. Hippocampal neurodegenerative and histological parameters as well as cyclic AMP response element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF) levels were assessed. Alcohol impaired cognition, and concurrent therapy with various minocycline doses attenuated alcohol-induced cognition disturbances. Additionally, alcohol administration boosted lipid peroxidation and levels of glutathione in oxidized form (GSSG), tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), and Bax protein, while decreased reducing type of glutathione (GSH), Bcl-2 protein, phosphorylated CREB, and BDNF levels in rat hippocampus. Alcohol also decreased the activity in the hippocampus of superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GR). In comparison, minocycline attenuated alcohol-induced neurodegeneration; elevating expression levels of P-CREB and BDNF and inhibited alcohol induced histopathological changes in both dentate gyrus (DG) and CA1 of hippocampus. Thus, minocycline is likely to provide neuroprotection against alcohol-induced neurodegeneration through mediation of the P-CREB/BDNF signaling pathway.
journal_name
Fundam Clin Pharmacoljournal_title
Fundamental & clinical pharmacologyauthors
Motaghinejad M,Mashayekh R,Motevalian M,Safari Sdoi
10.1111/fcp.12584subject
Has Abstractpub_date
2020-06-24 00:00:00eissn
0767-3981issn
1472-8206pub_type
杂志文章abstract::The maturation of the N-acetyltransferase-dependent AFMU production from caffeine was studied during infancy. The group of children (N = 14) consisted of 4 premature newborn infants and ten 1-19 month-old infants who received caffeine citrate solution for the treatment and prevention of apnea. Caffeine, AFMU, 1X and 9...
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