New tritarget small molecules combining Ca2+ channels blockade, cholinesterase, and H3 receptor inhibition were obtained by multicomponent synthesis. Compound 3p has been identified as a very promising lead, showing good Ca2+ channels blockade activity (IC50 = 21 ± 1 μM), potent affinity against hH3R (Ki = 565 ± 62 nM), a moderate but selective hBuChE inhibition (IC50 = 7.83 ± 0.10 μM), strong antioxidant power (3.6 TE), and ability to restore cognitive impairment induced by lipopolysaccharide.

• MeSH
• Alzheimerova nemoc farmakoterapie   metabolismus   MeSH
• blokátory kalciových kanálů chemie   farmakologie   MeSH
• cholinesterasové inhibitory chemie   farmakologie   MeSH
• knihovny malých molekul chemie   farmakologie   MeSH
• lidé MeSH
• myši MeSH
• nádorové buňky kultivované MeSH
• neuroblastom farmakoterapie   metabolismus   MeSH
• neuroprotektivní látky chemie   farmakologie   MeSH
• poruchy paměti farmakoterapie   metabolismus   MeSH
• receptory histaminu H3 chemie   MeSH
• vazodilatancia chemie   farmakologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• blokátory kalciových kanálů MeSH
• cholinesterasové inhibitory MeSH
• knihovny malých molekul MeSH
• neuroprotektivní látky MeSH
• receptory histaminu H3 MeSH
• vazodilatancia MeSH

The adipokinetic and red pigment-concentrating hormone (AKH/RPCH) family of peptides controls fat, carbohydrate, and protein metabolism in insects. In our previous study, we showed that AKH possesses antidepressant, anxiolytic, and analgesic effects, causes hyperlocomotion, and exerts neuroprotective effects and increased brain neurotrophic factors in mice. The aim of this study was to investigate the effects of Anax imperator AKH (Ani-AKH), Libellula auripennis AKH (Lia-AKH), and Phormia-Terra hypertrehalosemic hormone (Pht-HrTH) on MK-801-induced memory deterioration in the active allothetic place avoidance test (AAPA) and MK-801-induced sensorimotor gating deficit in the prepulse inhibition test (PPI). In the AAPA task, Long-Evans rats were treated with Ani-AKH (2 mg/kg), Lia-AKH (2 mg/kg), Pht-HrTH (2 mg/kg), MK-801 (0.15 mg/kg), and the combination of MK-801 with the hormones subchronically. In the prepulse inhibition test, Wistar albino rats were treated with Ani-AKH (1 mg/kg), Lia-AKH (1 mg/kg), Pht-HrTH (1 mg/kg), MK-801 (0.1 mg/kg), or the combination of MK-801 with hormones acutely before the test. In our study, Ani-AKH (2 mg/kg), Lia-AKH (2 mg/kg), and Pht-HrTH (2 mg/kg) reversed MK-801 (0.15 mg/kg)-induced cognitive memory impairment effects in the AAPA task. Lia-AKH (1 mg/kg) significantly potentiated the MK-801-induced PPI disruption, while Ani-AKH (1 mg/kg) partially potentiated the impairment caused by MK-801, and Pht-HrTH did not modify the effect of MK-801. In conclusion, AKH had no effect in sensorimotor gating deficits in the PPI test in schizophrenia model while AKH improved memory in the schizophrenia model of MK-801.

• Klíčová slova
• MK-801, adipokinetic hormone, rat, schizophrenia,
• MeSH
• anxiolytika farmakologie   MeSH
• dizocilpinmaleát farmakologie   MeSH
• hmyzí hormony farmakologie   MeSH
• krysa rodu Rattus MeSH
• kyselina pyrrolidonkarboxylová analogy a deriváty   farmakologie   MeSH
• modely nemocí na zvířatech MeSH
• neuropeptidy farmakologie   MeSH
• neuroprotektivní látky MeSH
• oligopeptidy farmakologie   MeSH
• paměť účinky léků   MeSH
• peptidy farmakologie   MeSH
• poruchy paměti chemicky indukované   farmakoterapie   MeSH
• potkani Long-Evans MeSH
• potkani Wistar MeSH
• schizofrenie chemicky indukované   farmakoterapie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• adipokinetic hormone MeSH Prohlížeč
• anxiolytika MeSH
• dizocilpinmaleát MeSH
• hmyzí hormony MeSH
• hypertrehalosemic hormone MeSH Prohlížeč
• kyselina pyrrolidonkarboxylová MeSH
• neuropeptidy MeSH
• neuroprotektivní látky MeSH
• oligopeptidy MeSH
• peptidy MeSH
• red pigment-concentrating hormone MeSH Prohlížeč

Obesity and type 2 diabetes mellitus (T2DM) were characterized as risk factors for Alzheimer's disease (AD) development. Subsequently, T2DM drugs, such as liraglutide, were proven to be neuroprotective compounds attenuating levels of amyloid deposits, and tau hyperphosphorylation, both hallmarks of AD. The central anorexigenic effects of liraglutide inspired us to examine the potential neuroprotective effects of palm11-PrRP31, a strong anorexigenic analog with glucose-lowering properties, in THY-Tau22 mice overexpressing mutated human tau, a model of AD-like tau pathology. Seven-month-old THY-Tau22 mice were subcutaneously infused with palm11-PrRP31 for 2 months. Spatial memory was tested before and after the treatment, using a Y-maze. At the end of the treatment, mice were sacrificed by decapitation and hippocampi were dissected and analyzed by immunoblotting with specific antibodies. Treatment with palm11-PrRP31 resulted in significantly improved spatial memory. In the hippocampi of palm11-PrRP31-treated THY-Tau22 mice, tau protein phosphorylation was attenuated at Thr231, Ser396, and Ser404, the epitopes linked to AD progression. The mechanism of this attenuation remains unclear, since the activation of those kinases most implicated in tau hyperphosphorylation, such as GSK-3β, JNK, or MAPK/ERK1/2, remained unchanged by palm11-PrRP31 treatment. Furthermore, we observed a significant increase in the amount of postsynaptic density protein PSD95, and a non-significant increase of synaptophysin, both markers of increased synaptic plasticity, which could also result in improved spatial memory of THY-Tau22 mice treated with palm11-PrRP31. Palm11-PrRP31 seems to be a potential tool for the attenuation of neurodegenerative disorders in the brain. However, the exact mechanism of its action must be elucidated.

• Klíčová slova
• Alzheimer’s disease, THY-Tau22 mice, palm11-PrRP31, spatial memory, synaptic plasticity, tau hyperphosphorylation,
• MeSH
• bludiště - učení účinky léků   fyziologie   MeSH
• fosforylace účinky léků   MeSH
• hipokampus účinky léků   metabolismus   patologie   MeSH
• hormon uvolňující prolaktin analogy a deriváty   farmakologie   terapeutické užití   MeSH
• krátkodobá paměť účinky léků   fyziologie   MeSH
• modely nemocí na zvířatech MeSH
• myši transgenní MeSH
• neuroprotektivní látky farmakologie   MeSH
• poruchy paměti farmakoterapie   metabolismus   patologie   MeSH
• prostorová paměť účinky léků   fyziologie   MeSH
• proteiny tau metabolismus   MeSH
• tauopatie farmakoterapie   metabolismus   patologie   psychologie   MeSH
• zvířata MeSH
• Check Tag
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• hormon uvolňující prolaktin MeSH
• Mapt protein, mouse MeSH Prohlížeč
• neuroprotektivní látky MeSH
• palm11-PrRP31 MeSH Prohlížeč
• proteiny tau MeSH

Pineal melatonin biosynthesis is regulated by the circadian clock located in the suprachiasmatic nucleus of the hypothalamus. Melatonin has been found to modulate the learning and memory process in human as well as in animals. Endogenous melatonin modulates the process of newly acquired information into long-term memory, while melatonin treatment has been found to reduce memory deficits in elderly people and in various animal models. However, the mechanisms mediating the enhancing effect of melatonin on memory remain elusive. This review intends to explore the possible mechanisms by looking at previous data on the effects of melatonin treatment on memory performance in rodents.

• MeSH
• hlodavci MeSH
• lidé MeSH
• melatonin farmakologie   terapeutické užití   MeSH
• modely nemocí na zvířatech MeSH
• paměť účinky léků   MeSH
• poruchy paměti farmakoterapie   patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• melatonin MeSH

Humanin (HN) and its analogues have been shown to protect cells against death induced by various Alzheimer's disease (AD) genes and amyloid-beta-peptides in vitro; the analogues [Gly(14)]-HN and colivelin have also been shown to be potent in reversing learning and memory impairment induced by scopolamine or quinuclidinyl benzilate (QNB) in mice or rats in vivo using the Y-maze or multiple T-maze tests. This paper describes the activity of new peptides of the HN family, after i.p. administration, on QNB-induced impairment of spatial memory in the multiple T-maze test in rats. The following peptides have been studied: HN analogues truncated either on the C- or N-terminus, or analogues having a tert-Leu in place of Leu in the central part of the molecule, the active HN core PAGASRLLLLTGEIDLP (RG-PAGA) and its analogues having three or five leucines instead of four, and finally the recently described hybrid peptide colivelin (i.e. a peptide having the activity-dependent neurotrophic factor SALLRSIPA attached to the N-terminus of the active RG-PAGA) and its des-Leu- and plus-Leu-analogues. While the truncated analogues and most of the tert-Leu containing analogues were devoid of activity, the analogues of the RG-PAGA were active, i.e. they reversed the impairment of spatial memory irrespective of the number of Leu present in their sequence. The highest activity was shown by colivelin and its des-Leu-analogue. These results demonstrate the potential of HN analogues in the modulation of the cholinergic system, which plays an important role in the cognitive deficits associated with AD and other neurodegenerative diseases.

• MeSH
• bludiště - učení účinky léků   MeSH
• chinuklidinylbenzilát MeSH
• intracelulární signální peptidy a proteiny terapeutické užití   MeSH
• krysa rodu Rattus MeSH
• neuroprotektivní látky terapeutické užití   MeSH
• orientace účinky léků   MeSH
• peptidy farmakologie   terapeutické užití   MeSH
• poruchy paměti chemicky indukované   farmakoterapie   prevence a kontrola   MeSH
• potkani Wistar MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• chinuklidinylbenzilát MeSH
• humanin MeSH Prohlížeč
• intracelulární signální peptidy a proteiny MeSH
• neuroprotektivní látky MeSH
• peptidy MeSH

Humanin and its analogues have been shown to protect cells against death induced by various Alzheimer's disease genes and amyloid-beta-peptides in vitro: the analogue [Gly14]-humanin has also been shown to be potent in reversing learning and memory impairment induced by scopolamine in mice in vivo. It is important to validate these results by using other behavioral methods. In this study, the effect of [Gly14]-humanin and des-Leu-PAGA, another analogue (0.2 micromol kg(-1), i.p.) on the 3-quinuclidinyl benzilate-induced (2 mg kg(-1), i.p.) impairment of spatial memory in the multiple T-maze in rats has been evaluated. Both peptides reversed the impairment of spatial memory. These results indicate the potential of humanin analogues in modulation of the cholinergic system.

• MeSH
• intracelulární signální peptidy a proteiny MeSH
• krysa rodu Rattus MeSH
• peptidy aplikace a dávkování   chemická syntéza   farmakologie   MeSH
• poruchy paměti chemicky indukované   farmakoterapie   MeSH
• potkani Wistar MeSH
• proteiny aplikace a dávkování   chemická syntéza   farmakologie   MeSH
• radioizotopy uhlíku MeSH
• sekvence aminokyselin MeSH
• skopolamin MeSH
• vztahy mezi strukturou a aktivitou MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• humanin MeSH Prohlížeč
• intracelulární signální peptidy a proteiny MeSH
• peptidy MeSH
• proteiny MeSH
• radioizotopy uhlíku MeSH
• skopolamin MeSH

Our previous studies showed that the nootropic drug Cerebrolysin, applied immediately after the traumatic or excitotoxic brain lesion influenced spatial learning and memory. Long-lasting ameliorative effect of Cerebrolysin was found after its 4-week-administration, while two-week-treatment had only temporal effect. With the aim to verify the capability of Cerebrolysin to restore chronically deteriorated learning and memory. The drug was applied 4 months after lesioning the rat's CNS. The present study shows that Cerebrolysin restored learning capability of the lesioned rats. Although their spatial memory was improved in comparison to lesion untreated controls, it did not reach the level of intact controls. The effect was more pronounced after the application of 1.25 ml/kg b. w. of Cerebrolysin than after the application of 2.5 ml/kg b. w.

• MeSH
• aminokyseliny terapeutické užití   MeSH
• chování zvířat účinky léků   MeSH
• krysa rodu Rattus MeSH
• nootropní látky terapeutické užití   MeSH
• poranění mozku komplikace   patologie   psychologie   MeSH
• poruchy paměti farmakoterapie   etiologie   MeSH
• poruchy učení farmakoterapie   etiologie   MeSH
• potkani Long-Evans MeSH
• vnímání prostoru účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• aminokyseliny MeSH
• cerebrolysin MeSH Prohlížeč
• nootropní látky MeSH

In an attempt to compare effects of different neurotrophic factors on impaired memory function, young adult naive rats were trained to find the hidden platform in the Morris water maze (3 consecutive days, eight trials/day). The fimbria-fornix was unilaterally removed by aspiration and nerve growth factor (NGF) (11 micrograms/ml and 0.5 microgram/ml; groups NGF and ngf, respectively) or basic fibroblast growth factor (bFGF) (0.2 microgram/ml, group FGF) were applied via intra-cerebroventricular infusion by the osmotic minipump (flow rate 0.5 microliter/h, 14 days). Nootropic drug Cerebrolysin (EBEWE Arzneitmittel; 2.5 ml/kg/day, group CER) was applied via intraperitoneal injection (14 days). One group was formed by the rats treated with NGF (11 micrograms/ml) and Cerebrolysin (group NGFCER). Non-lesioned and lesioned only rats served as controls (groups INT and LES). After a 14-day treatment, rats were tested using the retention test (1 day, four trials). On the next day, the rats were tested using transfer test (3 days, eight trials/day). Escape latency and length of trajectory was recorded. Groups NGF, ngf, FGF and LES were similarly impaired in their ability to retrieve the old position of the platform (retention test), as well as in their ability to navigate to the new position of the platform (transfer test). In the latter, NGF group significantly differed from lesioned animals. Groups CER and NGFCER were comparable to group INT in the retention or transfer test. It is concluded that anterograde amnesia elicited by fimbria-fornix lesion can be abbreviated by NGF and/or CER, while retrograde amnesia is absent only in rats treated by CER. No short-term influence of bFGF was found. It is suggested that biochemical systems other than the cholinergic one are involved.

• MeSH
• aminokyseliny farmakologie   MeSH
• bludiště - učení účinky léků   MeSH
• fibroblastový růstový faktor 2 farmakologie   MeSH
• hipokampus cytologie   fyziologie   MeSH
• krysa rodu Rattus MeSH
• neurotrofní faktory farmakologie   MeSH
• nootropní látky farmakologie   MeSH
• parasympatický nervový systém cytologie   účinky léků   MeSH
• poruchy paměti farmakoterapie   psychologie   MeSH
• viabilita buněk účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• aminokyseliny MeSH
• cerebrolysin MeSH Prohlížeč
• fibroblastový růstový faktor 2 MeSH
• neurotrofní faktory MeSH
• nootropní látky MeSH

• MeSH
• ergotaminy terapeutické užití   MeSH
• inbrední kmeny potkanů MeSH
• krysa rodu Rattus MeSH
• poruchy paměti farmakoterapie   MeSH
• psychotropní léky terapeutické užití   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• ergotaminy MeSH
• psychotropní léky MeSH