Leishmaniasis, as a tropical and subtropical disease, is endemic in more than 90 countries around the world. Today, cutaneous leishmaniasis (CL) that affects more than 1.5 million people per year lacks a definitive treatment approach. Imatinib is an anticancer drug that inhibits the abnormal function of Bcr-Abl due to its tyrosine kinase inhibitor, and that was the reason why the drug was tested for CL treatment because protein kinases are essential enzymes in the Leishmania genus. In this study, the L. major CL model of Balb/c mice was produced by injection of the cultured metacyclic form of parasite at the base of the tail. The possible recovery of CL ulcers and determination of the optimum dose of imatinib against Leishmania amastigotes were evaluated. A significant decrease was observed in mice treated with amphotericin B (positive control group) as well as imatinib 50 mg/kg compared to the unreceived drug, negative control group (P<0.05). This study could be promising in gaining insight into the potential of imatinib as an effective treatment approach against CL.
Citation: Mohsen Moslehi, Fatemeh Namdar, Mahsa Esmaeilifallah, Fariba Iraji, Bahareh Vakili, Fatemeh Sokhanvari, Seyed-Mohsen Hosseini, Faham Khamesipour, Zahra Sebghatollahi, Sayed-Hossein Hejazi. Study of therapeutic effect of different concentrations of imatinib on Balb/c model of cutaneous leishmaniasis[J]. AIMS Microbiology, 2020, 6(2): 152-161. doi: 10.3934/microbiol.2020010
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Leishmaniasis, as a tropical and subtropical disease, is endemic in more than 90 countries around the world. Today, cutaneous leishmaniasis (CL) that affects more than 1.5 million people per year lacks a definitive treatment approach. Imatinib is an anticancer drug that inhibits the abnormal function of Bcr-Abl due to its tyrosine kinase inhibitor, and that was the reason why the drug was tested for CL treatment because protein kinases are essential enzymes in the Leishmania genus. In this study, the L. major CL model of Balb/c mice was produced by injection of the cultured metacyclic form of parasite at the base of the tail. The possible recovery of CL ulcers and determination of the optimum dose of imatinib against Leishmania amastigotes were evaluated. A significant decrease was observed in mice treated with amphotericin B (positive control group) as well as imatinib 50 mg/kg compared to the unreceived drug, negative control group (P<0.05). This study could be promising in gaining insight into the potential of imatinib as an effective treatment approach against CL.
The hippocampus plays a central role to form new episodic memory in various species including humans [1]. The hippocampal neurons seem to process variety of information,such as spatial location [2],temporal information [3],and emotional state [4] within specific episodes [5]. However,the critical mechanism how to sustain a piece of specific memory or what associates the memory fragment each other is still largely unknown.
Since selective blockade of long-term potentiation(LTP)induction by NMDA receptor antagonist impairs hippocampal learning [6],LTP has been considered as a cellular model of hippocampal memory [7]. In 2006,in vivo field EPSC recording study showed that hippocampal learning induces LTP in CA1 region of hippocampus [8]. Further,we revealed that learning-dependent synaptic delivery of AMPA receptors into the CA3-CA1 synapses is required for hippocampal learning [9]. Since there is no tetanus electrode in brain,endogenous trigger and /or the mechanism inducing the learning-dependent LTP were unknown.
I hypothesized acetylcholine(ACh)as an endogenous trigger of LTP,since the ACh release in the hippocampus increases during learning or exploration. Moreover,without electrode for tetanus stimulation,bath treatment of ACh agonist not only induces specific bursts [10] but also forms LTP in CA1 region of hippocampal slices [11]. Based on the hypothesis,I found that i)cholinergic trigger drives learning-dependent synaptic plasticity at excitatory and inhibitory synapses,and ii)learning requires the diversity of synaptic inputs in CA1 pyramidal neurons [12].
ACh seems to be necessary to strengthen the information-specific tagged CA1 synapses [13],depicted by hippocampal-cortical networks [14].
A number of studies suggest that ACh plays an important role in orchestrating majorhippocampal functions(Figure 1). In behavioural studies,ACh release increases during learning [15,16,17] and is positively correlated with learning performance [18,19]. Bilateral injections of scopolamine into the dorsal hippocampus impair spatial learning ability [20],suggesting that muscarinic ACh receptors mediate the formation of spatial memory. At the network level,ACh generates a theta rhythm [21] that modulates the induction of long-term potentiation(LTP)in hippocampal CA1 neurons [22]. Studies exploring a genetic deficiency of muscarinic ACh receptors(M1 or M2)further show the impairment of LTP in the CA1 region [23,24]. At the cellular level,both pyramidal and non-pyramidal neurons in the hippocampal CA1 area receive direct cholinergic afferents mediated by muscarinic receptors [25,26,27]. In vitro studies showed that bath application of carbachol,a cholinergic agonist,induces LTP in CA1 pyramidal neurons without electrical stimulus,suggesting that ACh in the hippocampus plays a principal role in the synaptic plasticity of the CA1 pyramidal neurons [11]. Furthermore,a recent study revealed an intracellular mechanism of ACh: focal activation of muscarinic ACh receptors in one CA1 pyramidal neuron induces Ca2+ release from inositol 1,4,5-trisphosphate-sensitive stores to induce LTP [28].
Figure 1. Schematic illustration of septo-hippocampal cholinergic neurons in rats. Exposure to serious episode induces ACh release in the hippocampus that activates hippocampal functions(Mitsushima et al,2008). I know,you remember where you were and what you were doing when serious events occur.
ACh in the hippocampus not only enhances plasticity at CA1 synapses,but also contribute to adult neurogenesis in the dentate gyrus,that is required for contextual memory [29]. Neurotoxic lesions of forebrain cholinergic neurons or long-term scopolamine treatment decreases the number of newborn cells in the dentate gyrus [30,31].
Although it is well established that cholinergic inputs from the medial septum modulate learning and memory,evidence for the cholinergic regulation of learning-induced synaptic plasticity is lacking. To investigate learning-induced synaptic modification in the hippocampus,we used the IA task(Figure 2). In this paradigm,rats are allowed to cross from an illuminated box to a dark box where an electric foot shock is delivered. Thus,rats learn to avoid the dark box and stay in the lighted one,which they would normally not prefer [8,9]. The tendency to avoid the dark box therefore indicates the acquisition of contextual memories. The rats avoided entering the dark box when it was associated with a mild electric shock(IA-trained),but not those given foot shock without any contextual experience(unpaired),or those allowed to simply explore the experimental cage(walk-through). Untrained control rats were kept in their home cages and were not exposed to the IA apparatus.
Figure 2.(a)Schema of inhibitory avoidance(IA)task. On the day of IA training,rats were placed in the light side of the box. When rats moved into the dark side box,we closed the door and applied electrical foot shock(1.6 mA)for 2 sec. The rats were returned to the home cage soon after the shock.(b)Even one training,rats well remember the episode,spending much longer time in the light box after training [12].
Cholinergic neurons within the basal forebrain provide the major projection to the neocortex and hippocampus [32]. Cortical regions receive cholinergic inputs mainly from the nucleus basalis magnocellularis(NBM)or the diagonal b and of Broca,whereas the hippocampus receivescholinergic inputs mostly from the medial septum and horizontal limb of the diagonal b and of
Broca [32]. Because the cholinergic projections are necessary to maintain learning and
memory [33,34],we hypothesized that in vivo monitoring of ACh release in the hippocampus is necessary to elucidate learning function. To measure ACh release,we have performed in vivo microdialysis studies in freely moving male rats. Briefly,a microdialysis probe with a semi-permeable membrane(0.5 mm in length)was inserted into a specific brain area via a surgically pre-implanted guide cannula. We perfused the inside of the membrane with artificial cerebrospinal fluid,and assayed ACh in dialysates using a high-performance liquid chromatography system. As a result,we observed long-lasting(≈60 min)ACh release in CA1 in IA-trained rats but not in untrained,unpaired,or walk-through controls(Figure 3)[12].
Figure 3.In vivoACh levels in the rat hippocampal CA1 region under different learning conditions.(a)Locations of the in vivo microdialysis probe in CA1.(b)Extracellular ACh levels increased significantly during IA training,and remained high for 60 min. In the unpaired or walk-through control animals,the ACh level increased,but only transiently [12]. Squares indicate the timing of the behavioral task. Error bars indicate ± sem.
Although it is well established that cholinergic inputs from the medial septum modulate learning and memory,evidence for the cholinergic regulation of learning-induced synaptic plasticity is lacking. By combining HSV-mediated in vivo gene delivery with in vitro patch-clamp recordings,we reported that contextual learning drives GluA1-containing AMPA receptors into hippocampal CA3-CA1 synapses. Double IA-training using two different contexts further drove AMPA receptors into the CA3-CA1 synapses [35]. More importantly,the synaptic delivery is required for contextual learning,since bilateral expression of AMPA receptor delivery blocker(MPR-DD)successfully impaired the contextual learning [9].
To further examine the learning-dependent synaptic plasticity,we recorded miniature EPSC(mEPSC at -60 mV) and miniature IPSC(mIPSC at 0 mV)from the same CA1 neuron under the presence of TTX(0.5 µM). Although control rats(untrained,unpaired,or walk through)show small mEPSC and mIPSC amplitudes,IA trained rats show significantly higher mEPSC and mIPSC amplitudes with much wider variation(Figure 4). These results suggest that each CA1 neuron has different excitatory or inhibitory synaptic inputs with wide electrophysiological variation.
Figure 4.A hour after the training,we prepared acute brain slices to analyze synaptic inputs in each CA1 neuron using patch clamp method. Each dot represents mean miniature EPSC and miniature IPSC responses in each CA1 neuron. The results suggest that IA training enhanced electrophysiological diversity of excitatory and inhibitory synapses. Muscarinic M1 ACh receptor antagonist blocked the training-dependent diversity of mEPSCs. In contrast,nicotinic a7 ACh receptor antagonist blocked the diversity of mIPSCs [12](. Red crosses represent means ± sem.).
Since I hypothesized that ACh is an intrinsic trigger of the synaptic plasticity,cholinergic receptor antagonist was microinjected into the CA1 neurons 15 min before the contextual learning. Microinjection of muscarinic M1 receptor antagonist(pirenzepine)into the CA1 successfully blocked the learning-dependent increase in mEPSC amplitude but not mIPSC amplitude. Conversely,microinjection of nicotinic a7receptor antagonist(methyllycaconitine)successfully blocked the learning-dependent increase in mIPSC amplitude but not mEPSC amplitude. In behaving rats,bilateral microinjections of pirenzepine or methyllycaconitine into CA1 successfully block the learning.
These results suggest that i)cholinergic trigger drives learning-dependent synaptic plasticity at excitatory and inhibitory synapses and ii)learning requires the diversity of synaptic inputs in CA1 pyramidal neurons [12]. Based on the results,I hypothesized that the diversity probably depicts cell-specific outputs processing experienced episodes after training(Figure 5). The mechanism of synaptic tagging at inhibitory synapses should be revealed in future.
Figure 5.Current hypothesis of learning & memory. Note that each CA1 neuron expresses barcode-like output after learning. Acetylcholine triggers learning-dependent synaptic plasticity of excitatory and inhibitory synapses,inducing electrophysiological diversity of excitatory and inhibitory synapses. To process experienced episodes,the diversity probably depends on information-specific-tagged CA1 synapses depicted by hippocampal-cortical networks.
We recently monitored in vivo multiple-unit spike activity of CA1 neurons before,during,and after exposure to a strong episode using male rats. Although spontaneous firing rate was low in habituated home cage,spontaneous high frequency firing suddenly observed for seconds during or soon after the strong episode. Then,minutes after the episode,short term but high frequency ripple-like(on/off)synchronized firing was clearly observed and sustained [36]. These observations provide crucial evidence supporting our hypothesis of learning and memory(Figure 5).
To determine a possible location of contextual memory,we made acute brain slices in four different CA1 areas(dorsal right,dorsal left,ventral right and ventral left)in untrained or IA-trained rats. We found that IA training induced synaptic plasticity in both side of dorsal hippocampus,but not in ventral hippocampus [37]. Non-stationary noise-analysis techniques further revealed that IA training significantly increased the number of open channels in dorsal hippocampus,but not in ventral hippocampus. These results suggest that learning-dependent synaptic plasticity occur in dorsal hippocampus bilaterally,but not in ventral hippocampus [38]. Considering our previous study to block AMPA receptor delivery [9],encoded contextual information seems to locate in both side of dorsal hippocampus.
To determine whether the encoding of context or retrieval induces synaptic change,we made acute brain slices in 6 different timing after IA training. We found that i)the encoding of context rather than retrieval induces both excitatory and inhibitory synaptic change and ii)the encoding quickly induces the plastic change within 10 min after the training [39].
We recently reported the developmental change in hippocampal ACh levels and contextual learning. Extracellular ACh levels in the dorsal hippocampus are low in juveniles,but increase significantly in adults. Simultaneous monitoring of ACh levels and spontaneous locomotor activity further demonstrated the development of ACh release. Although both juvenile and adult rats exhibited significant correlations between ACh levels and spontaneous activity,juveniles exhibited much more spontaneous activity than adults when they showed equivalent ACh levels. Similarly,low contextual learning performance in juveniles significantly increased,demonstrating a developmental trajectory of hippocampal function. In this report,we further revealed a developmental relationship between contextual learning and ACh level in the hippocampus [Freezing(sec)= 1171 ACh(pmol/20 min)+ 36].
More importantly,the ACh release in juveniles seems to be important to development of hippocampus and learning,since long-term treatment of scopolamine after weaning specifically impaired contextual learning without changing pain sensitivity,emotional state,and spontaneous activity. The findings,together with previous reports,lead to the hypothesis that juveniles require more spontaneous activity than adults to activate hippocampal functions. Our findings support the notion that every boy and girl requires sufficient spontaneous play in parks or nature to promote brain activity as well as physical activity [40].
In humans,aging seems to attenuate the ACh levels. Moreover,a reduction in ACh synthesis is known as a common feature of Alzheimer's disease [41,42,43]. The disease is the most common form of dementia [44] and is frequently accompanied by insomnia,poor concentration,and day night confusion [45,46]. The centrally active acetylcholinesterase inhibitor(donepezil)is effective in not only mild,but also moderate to severe cases [47,48],proving the importance of endogenous ACh in humans. We found neonatal sexual differentiation of the septo-hippocampal cholinergic system,suggesting sex-specific clinical strategies for Alzheimer’s disease [3]. Underst and ing the further detailed mechanism of ACh-triggered learning-dependent plasticity is essential for real improvements in therapy.
I declare no conflicts of interest in this paper.
| [1] |
Ghorbani M, Farhoudi R (2018) Leishmaniasis in humans: drug or vaccine therapy? Drug Des Devel Ther 12: 25-40. doi: 10.2147/DDDT.S146521
|
| [2] | Lindoso JA, Cunha MA, Queiroz IT, et al. (2016) Leishmaniasis–HIV coinfection: current challenges. HIV/AIDS 8: 147. |
| [3] |
Bahrami F, Harandi AM, Rafati S (2018) Biomarkers of cutaneous leishmaniasis. Front Cell Infect Microbiol 8: 222. doi: 10.3389/fcimb.2018.00222
|
| [4] |
Mendonça SC (2016) Differences in immune responses against Leishmania induced by infection and by immunization with killed parasite antigen: implications for vaccine discovery. Parasites Vectors 9: 492. doi: 10.1186/s13071-016-1777-x
|
| [5] |
Apostolopoulos N, Mitropoulou A, Thom N, et al. (2018) Update on therapy and prevention of canine leishmaniasis. Tierarztl Prax Ausg K Kleintiere Heimtiere 46: 315-322. doi: 10.15654/TPK-180089
|
| [6] | Kaiming B, Yuyang C, Songnian Z, et al. (2018) Current visceral leishmaniasis research: a research review to inspire future study. BioMed Res Intl 2018: 1-13. |
| [7] |
Norouzinezhad F, Ghaffari F, Norouzinejad A, et al. (2016) Cutaneous leishmaniasis in Iran: Results from an epidemiological study in urban and rural provinces. Asian Pac J Trop Biomed 6: 614-619. doi: 10.1016/j.apjtb.2016.05.005
|
| [8] |
Adriaensen W, Dorlo TPC, Guido V, et al. (2018) Immunomodulatory therapy of visceral leishmaniasis in human immunodeficiency virus-coinfected patients. Front Immunol 8: 1943. doi: 10.3389/fimmu.2017.01943
|
| [9] |
de Vries HJ, Reedijk SH, Schallig HD (2015) Cutaneous leishmaniasis: recent developments in diagnosis and management. Am J Clin Dermatol 16: 99-109. doi: 10.1007/s40257-015-0114-z
|
| [10] |
Alcântara LM, Ferreira TCS, Gadelha FR, et al. (2018) Challenges in drug discovery targeting TriTryp diseases with an emphasis on leishmaniasis. Int J Parasitol Drugs Drug Resist 8: 430-439. doi: 10.1016/j.ijpddr.2018.09.006
|
| [11] |
Hotez PJ, Bottazzi ME, Strych U (2016) New vaccines for the world's poorest people. Annu Rev Med 67: 405-417. doi: 10.1146/annurev-med-051214-024241
|
| [12] |
Moen MD, McKeage K, Plosker GL, et al. (2007) Imatinib: a review of its use in chronic myeloid leukaemia. Drugs 67: 299-320. doi: 10.2165/00003495-200767020-00010
|
| [13] |
O'Connell EM, Bennuru S, Steel C, et al. (2015) Targeting Filarial Abl-like Kinases: Orally Available, Food and Drug Administration–Approved Tyrosine Kinase Inhibitors Are Microfilaricidal and Macrofilaricidal. Int J Infect Dis 212: 684-693. doi: 10.1093/infdis/jiv065
|
| [14] |
Kesely KR, Pantaleo A, Turrini FM, et al. (2016) Inhibition of an erythrocyte tyrosine kinase with imatinib prevents Plasmodium falciparum egress and terminates parasitemia. PloS one 11. doi: 10.1371/journal.pone.0164895
|
| [15] |
Alvarez-Rueda N, Biron M, Le Pape (2009) Infectivity of Leishmania mexicana is associated with differential expression of protein kinase C-like triggered during a cell-cell contact. PLoS One 4. doi: 10.1371/journal.pone.0007581
|
| [16] |
Hodgson J (2001) ADMET—turning chemicals into drugs. Nat Biotechnol 19: 722-726. doi: 10.1038/90761
|
| [17] |
Potts RO, Guy RH (1992) Predicting skin permeability. Pharm Res 9: 663-669. doi: 10.1023/A:1015810312465
|
| [18] | Moslehi M, Namdar F, Esmaeilifallah M, et al. (2019) Evaluation of different concentrations of imatinib on the viability of Leishmania major: An In Vitro study. Adv Biomed Res 8. |
| [19] |
Ponte-Sucre A, Gamarro F, Dujardin JC, et al. (2017) Drug resistance and treatment failure in leishmaniasis: A 21st century challenge. PLoS Negl Trop Dis 11. doi: 10.1371/journal.pntd.0006052
|
| [20] |
Vakili B, Eslami M, Hatam GR, et al. (2018) Immunoinformatics-aided design of a potential multi-epitope peptide vaccine against Leishmania infantum. Int J Biol Macromol 120: 1127-1139. doi: 10.1016/j.ijbiomac.2018.08.125
|
| [21] |
Scott P, Novais FO (2016) Cutaneous leishmaniasis: immune responses in protection and pathogenesis. Nat Rev Immunol 16: 581-592. doi: 10.1038/nri.2016.72
|
| [22] |
Vakili B, Nezafat N, Zare B, et al. (2020) A new multi-epitope peptide vaccine induces immune responses and protection against Leishmania infantum in BALB/c mice. Med Microbiol Immunol 209: 69-79. doi: 10.1007/s00430-019-00640-7
|
| [23] |
Bekhit AA, El-Agroudy E, Helmy A, et al. (2018) Leishmania treatment and prevention: Natural and synthesized drugs. Eur J Med Chem 160: 229-244. doi: 10.1016/j.ejmech.2018.10.022
|
| [24] |
Vakili B, Nezafat N, Hatam GR, et al. (2018) Proteome-scale identification of Leishmania infantum for novel vaccine candidates: A hierarchical subtractive approach. Comput Biol Chem 72: 16-25. doi: 10.1016/j.compbiolchem.2017.12.008
|
| [25] |
Kennedy JA, Hobbs G (2018) Tyrosine kinase inhibitors in the treatment of chronic-phase CML: Strategies for frontline decision-making. Curr Hematol Malig Rep 13: 202-211. doi: 10.1007/s11899-018-0449-7
|
| [26] |
Katz N, Couto FFB, Araújo N (2013) Imatinib activity on Schistosoma mansoni. Mem Inst Oswaldo Cruz 108: 850-853. doi: 10.1590/0074-0276130207
|
| [27] |
Beckmann S, Long T, Scheld C, et al. (2014) Serum albumin and α-1 acid glycoprotein impede the killing of Schistosoma mansoni by the tyrosine kinase inhibitor Imatinib. Int J Parasitol Drugs Drug Resist 4: 287-295. doi: 10.1016/j.ijpddr.2014.07.005
|
| [28] |
Naula C, Parsons M, Mottram JC (2005) Protein kinases as drug targets in trypanosomes and Leishmania. Biochim Biophys Acta 1754: 151-159. doi: 10.1016/j.bbapap.2005.08.018
|
| [29] |
Handman E, Bullen DV (2002) Interaction of Leishmania with the host macrophage. Trends Parasitol 18: 332-334. doi: 10.1016/S1471-4922(02)02352-8
|
| [30] |
Sanderson L, Yardley V, Croft SL (2014) Activity of anticancer protein kinase inhibitors against Leishmania spp. J Antimicrob Chemother 69: 1888-1891. doi: 10.1093/jac/dku069
|
| [31] |
Matsushita M, Kawaguchi M (2018) Immunomodulatory effects of drugs for effective cancer immunotherapy. J Oncol 2018. doi: 10.1155/2018/8653489
|
| [32] |
Hahn T, Polanczyk MJ, Borodovsky A, et al. (2013) Use of anticancer drugs, mitocans, to enhance the immune responses against tumors. Curr Pharm Biotechnol 14: 357-376. doi: 10.2174/1389201011314030010
|
| [33] |
Al-Abdely HM, Graybill JR, Bocanegra R, et al. (1998) Efficacies of KY62 against Leishmania amazonensis and Leishmania donovani in experimental murine cutaneous leishmaniasis and visceral leishmaniasis. Antimicrob Agents Chemother 42: 2542-2548. doi: 10.1128/AAC.42.10.2542
|
| [34] | Dahiya M, Dureja H (2016) Central composite designed imatinib-loaded magnetic nanoparticles. Recent Pat Nanotechnol 6: 146-155. |
| 1. | Eduardo Mercado III, Learning-Related Synaptic Reconfiguration in Hippocampal Networks: Memory Storage or Waveguide Tuning?, 2015, 2, 2373-7972, 28, 10.3934/Neuroscience.2015.1.28 |
Figures(2) / Tables(2)
Mohsen Moslehi, Fatemeh Namdar, Mahsa Esmaeilifallah, Fariba Iraji, Bahareh Vakili, Fatemeh Sokhanvari, Seyed-Mohsen Hosseini, Faham Khamesipour, Zahra Sebghatollahi, Sayed-Hossein Hejazi. Study of therapeutic effect of different concentrations of imatinib on Balb/c model of cutaneous leishmaniasis[J]. AIMS Microbiology, 2020, 6(2): 152-161. doi: 10.3934/microbiol.2020010
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