Abstract：
:The earliest hallmarks of sporadic Alzheimer's disease (sAD) are impaired glucose metabolism, chronic neuroinflammation, diminished synaptic plasticity and subsequent cognitive decline. The safest antidiabetic drug metformin has shown both glucose metabolism-improving and cognition-enhancing action in type 2 diabetes patients and diabetic model animals. However, metformin has not been previously studied in intracerebroventricular streptozocin (STZ)-induced model of sAD. Therefore, our aim was to assess the preventive action of metformin in sAD model-rats. Firstly, the actions of metformin (75 and 100 mg/kg) on cognitive functions and sociability were examined. Secondly, we wanted to identify whether behavioral effects of metformin were provided via its action on brain glucose transport, neuronal/glial uptake and metabolism. Thirdly, the effects of metformin on neuroinflammation, acetylcholine esterase density and activity, as well as on synaptic plasticity were determined. Our results showed that metformin reversed STZ-induced impairments in spatial learning/memory performance and sociability, coinciding with normalization of brain glucose transport, uptake and metabolism. Microgliosis and astrogliosis were ameliorated by metformin in sAD model rats. Metformin also preserved hippocampal synaptic plasticity and normalized acetylcholine cleavage in the cortical and hippocampal tissues, as well as inhibited acetylcholine esterase activity in vitro. These data indicate the promise of further research of metformin in early brain pathologies to stop neurodegenerative before severe cognitive decline occurs.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Pilipenko V,Narbute K,Pupure J,Langrate IK,Muceniece R,Kluša Vdoi
10.1016/j.ejphar.2020.173290subject
Has Abstractpub_date
2020-08-15 00:00:00pages
173290eissn
0014-2999issn
1879-0712pii
S0014-2999(20)30382-4journal_volume
881pub_type
杂志文章abstract：:The administration of ethyl beta-carboline-3-carboxylate (beta-CCE), a ligand for benzodiazepine receptors, did not affect the cerebellar cyclic GMP level in mice, but giving beta-CCE together with diazepam significantly inhibited the diazepam-induced decrease in cyclic GMP. The fact that no antagonism was observed wh...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(82)90065-6
更新日期：1982-05-21 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(97)01250-8
更新日期：1997-10-08 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2014.07.004
更新日期：2014-10-15 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(01)01397-8
更新日期：2001-11-16 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(87)90431-6
更新日期：1987-06-19 00:00:00
abstract：:The structure-activity relationships of 35 novel derivatives of 2-(carboxypropyl)-3-amino-4-methyl-6-phenyl pyridazine (SR 95103) were examined as gamma-aminobutyric acid (GABA) antagonists in the flap preparation of the parasitic nematode, Ascaris suum, using a two-microelectrode current-clamp technique. All but one ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(94)00778-6
更新日期：1995-03-24 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(88)90437-2
更新日期：1988-01-19 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(91)90009-f
更新日期：1991-12-10 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2006.09.034
更新日期：2006-12-28 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(93)90689-f
更新日期：1993-01-26 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(88)90178-1
更新日期：1988-03-15 00:00:00
abstract：:This study assessed the effects of intracerebroventricular administration of selective agonists and antagonists for tachykinin NK1 and NK2 receptors on performance of mice in the elevated plus-maze, an ethological model of anxiety. Mice were treated with either vehicle (5 microliters) or 1, 10, 100 or 500 pmol of subs...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(96)00390-1
更新日期：1996-09-05 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2012.06.002
更新日期：2012-09-05 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(95)00457-2
更新日期：1995-11-24 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(92)90409-w
更新日期：1992-01-21 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2007.06.012
更新日期：2007-10-01 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2011.02.028
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(97)01427-1
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journal_title：European journal of pharmacology
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doi：10.1016/j.ejphar.2003.09.005
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journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
pub_type： 杂志文章
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journal_title：European journal of pharmacology
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doi：10.1016/j.ejphar.2006.03.038
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2015.11.040
更新日期：2016-01-05 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(79)90321-2
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journal_title：European journal of pharmacology
pub_type： 杂志文章
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(80)90495-1
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(84)90324-8
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(03)01724-2
更新日期：2003-05-23 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(89)90361-0
更新日期：1989-08-03 00:00:00
abstract：:In view of the scarce information about the analgesic mechanism of kappa-opioid receptor agonists, the objective of the present study was to determine whether nitric oxide (NO) is involved in the peripheral antinociception of bremazocine, a kappa-opioid receptor agonist. Three drugs all interfering with the L-arginine...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(02)02275-6
更新日期：2002-11-01 00:00:00
