Beneficial effects of resveratrol on scopolamine but not mecamylamine induced memory impairment in the passive avoidance and Morris water maze tests in rats

Gacar, Nejat; Mutlu, Oğuz; Utkan, Tijen; Çelikyurt, İpek Komşuoğlu; Göçmez, S.S.; Ulak, Güner

doi:10.1016/j.pbb.2011.05.017

Cited by 80 publications

(48 citation statements)

References 43 publications

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“…After 24 hours, a retention testing session was performed without application of an electric shock. The latency for entering the dark compartment (four paws in) was recorded and was used for analysis (19,38).…”

Section: Passive Avoidance Testmentioning

confidence: 99%

The effect of omega-3 on cognition in hypothyroid adult male rats

Allah¹,

Gomaa²,

Sayed³

2014

Acta Physiologica Hungarica

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Thyroid hormones and omega-3 are essential for normal brain functions. Recent studies have suggested that omega-3 may protect against the risk of dementia. The aim of this study was to investigate the effect of hypothyroidism on spatial learning and memory in adult male rats, the underlying mechanisms and the possible therapeutic value of omega-3 supplementation. Thirty male rats were divided into three groups; control, hypothyroid and omega-3 treated. Hypothyroidism induced significant deficits in working and reference memories in radial arm maze, retention deficits in passive avoidance test and impaired intermediate and long-term memories in novel object recognition test. Serum total antioxidant capacity (TAC) and hippocampal serotonin and γ-aminobutyric acid (GABA) levels were decreased in the hypothyroid group as compared to the control group. Moreover, the hippocampus of hypothyroid rats showed marked structural changes as diffuse vacuolar degeneration and distortion of the pyramidal cells. Immunohistochemistry showed that the expression of Cav1.2 (the voltage dependent LTCC alpha 1c subunit) protein was increased in the hypothyroid group as compared to the control group. Omega-3 supplementation ameliorated memory deficits, increased TAC, decreased the structural changes and decreased the expression of Cav1.2 protein. In conclusion omega-3 could be useful as a neuroprotective agent against hypothyroidism-induced cognitive impairment.Keywords: hypothyroidism, cognition, omega-3, Cav1.2, GABA and serotonin Thyroid hormones play an important role in the development and the normal function of CNS by different mechanisms. They regulate synaptic transmission (15), modulate the synthesis and turnover of neurotransmitters and modify the sensitivity of their receptors (42, 51). They modulate signal transduction pathways in the CNS through Ca 2+ channels. L-type voltagesensitive Ca 2+ (Cav) channel (L-VSCC) mediates long lasting Ca 2+ currents (55) that play important roles in neurotransmitters release, second messenger cascades and gene regulation (28). L-VSCCs localize prominently on neuronal cell bodies and proximal dendrites (24). They consist of five subunits: α1, α2, β, γ and δ (40); α1 subunit is the ion-conducting pore and contains the binding sites for dihydropyridine (9). There are two different L-VSCC α1 subunits: α1C (Cav1.2) and α1D (Cav1.3) (47). Growing evidence has suggested that excessive Ca 2+ influx through L-VSCCs may be detrimental to memory (55). Moreover, L-VSCC currents were reported to be increased in the hippocampus of aged rats and rabbits and thus, had been implicated in aged-related memory deficits (50). Omega-3 polyunsaturated fatty acids (PUFAs), including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are major components of neuronal membranes and have a wide range of functions including neural growth (18), neuroprotection and modulation of

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Section: Passive Avoidance Testmentioning

confidence: 99%

The effect of omega-3 on cognition in hypothyroid adult male rats

Allah¹,

Gomaa²,

Sayed³

2014

Acta Physiologica Hungarica

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“…Resveratrol (3,5,4'-trihydroxy-trans-stilbene), a phytoalexin from this plant, has been reported to improve scopolaminebut not mecamylamine-induced memory impairment in rats, in both passive avoidance and Morris water maze tests. The interaction of resveratrol with muscarinic cholinergic receptors has also been suggested by the same authors (9). The neuroprotective effects of resveratrol have been reported by a number of studies which include the protection of dopaminergic neurons from MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) induced toxicity in mice.…”

Section: Introductionmentioning

confidence: 70%

The Differential Effects of Resveratrol and trans-ε-Viniferin on the GABA-Induced Current in GABAA Receptor Subtypes Expressed in Xenopus Laevis Oocytes

Groundwater

Hamid

et al. 2015

J Pharm Pharm Sci

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-Purpose:The natural products resveratrol and trans-ε-viniferin have been reported to have many beneficial effects, which include the enhancement of cognition and memory. There have been no studies which have reported the effects of these compounds on the different GABAA receptor subtypes and this study aimed to address this. Methods: The effects of both resveratrol, and its dimer, trans-ε-viniferin, have been investigated on different GABAA receptor subtypes expressed in Xenopus laevis oocytes, using the twoelectrode voltage clamp technique. Results: Resveratrol induced a current of 22 ± 3.53 nA in the α1β2γ2L subtype of the GABAA receptor (but not in the α5β3γ2L and α2β2γ2L subtypes) when applied alone. It also positively modulated the GABA-induced current (IGABA) in α1β2γ2L receptors, in a dose-dependent manner (EC50 58.24 μM). The effects of resveratrol were not sensitive to the benzodiazepine antagonist flumazenil. trans-ε-Viniferin exhibited a different pattern of activity to resveratrol; it alone had no effect on any of the subtypes, but it did negatively modulate the GABA-induced current (IGABA) in all three subtypes. The greatest inhibition was found in the α1β2γ2L subtype (IC50 5.79 μM), with the inhibition in the α2β2γ2L (IC50 of 19.08 μM) and α5β3γ2L (IC50 of 21.05 μM) subtypes being similar. The effects of trans-ε-viniferin in α1β2γ2L and α2β2γ2L receptors were also not sensitive to the benzodiazepine antagonist flumazenil while, in the α5β3γ2L subtype the effect was not sensitive to the inverse agonist L-655,708, indicating different binding sites for this molecule. Conclusions: The results of the present study indicate that both resveratrol and trans-ε-viniferin modulate the GABA-induced current in different ways, and that trans-ε-viniferin may be a lead compound for the discovery of agents which selectively inhibit the GABA-induced current in α1-containing subtypes.

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“…As a standard amnesic drug, scopolamine is frequently used in similar 50 was not established, the therapeutic dose was approximated from a previous study 36 . studies [32][33][34][35] . In this study, scopolamine was successfully substituted by another non-selective muscarinic receptor antagonist -QNB.…”

Section: Discussionmentioning

confidence: 99%

The effects of novel 7-MEOTA-donepezil like hybrids and N-alkylated tacrine analogues in the treatment of quinuclidinyl benzilate-induced behavioural deficits in rats performing the multiple T-maze test

Mišík¹,

Korábečný²,

Nepovimová³

et al. 2015

BIOMED PAP

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Aims. The number of approved drugs for the clinical treatment of Alzheimer disease remains limited. For this reason, there is extensive search for novel therapies. Of these, cholinesterase inhibitors have some proven benefit in slowing the disease progression and still remain the first-line therapeutic approach. In this study, the pro-cognitive effect of four novel tacrine-related inhibitors was evaluated and compared with the standards, tacrine and donepezil. Methods. Wistar rats trained to perform the multiple T-maze were treated intra-peritoneally with the anticholinergic agent 3-quinuclidinyl benzilate (QNB, 2.0 mg/kg), followed 30 min later by another injection containing a therapeutic dose of standard or novel cholinesterase inhibitor. The rats were repeatedly subjected to the multiple T-maze task at several time points following QNB administration (1, 24, 48 and 72 h). The passage time and number of errors were recorded. The inhibitory potential of selected therapeutic doses was assessed in a separate in vivo experiment using a spectrophotometric method. Results. QNB significantly impaired the performance of the rats within 48 h. The four novel cholinesterase inhibitors attenuated the effect of QNB at 1 h, 24 h and 48 h test intervals. The novel compounds resulted in brain cholinesterase inhibition ranging from 5.4 to 11.3 %, and their effect on the QNB-induced deficit recorded in the T-maze performance was comparable to that of the standards or higher at some time points. Conclusion: The best result was achieved with derivative 4, followed by derivatives 2 and 3, suggesting that these compounds could be candidates for the treatment of Alzheimer disease.

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Beneficial effects of resveratrol on scopolamine but not mecamylamine induced memory impairment in the passive avoidance and Morris water maze tests in rats

Cited by 80 publications

References 43 publications

The effect of omega-3 on cognition in hypothyroid adult male rats

The effect of omega-3 on cognition in hypothyroid adult male rats

The Differential Effects of Resveratrol and trans-ε-Viniferin on the GABA-Induced Current in GABAA Receptor Subtypes Expressed in Xenopus Laevis Oocytes

The effects of novel 7-MEOTA-donepezil like hybrids and N-alkylated tacrine analogues in the treatment of quinuclidinyl benzilate-induced behavioural deficits in rats performing the multiple T-maze test

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