Importantly, the short half-life of 1NMPP1 (less than 1 hr) (Wang

Importantly, the short half-life of 1NMPP1 (less than 1 hr) (Wang et al., 2003), together with direct biochemical evidence excluding persistent inhibition (G.L., unpublished data), establishes the transient nature of the kinase inhibition. The virtual elimination of spontaneous recurrent seizures and associated anxiety-like behavior were evident long after discontinuation

of TrkB kinase inhibition, demonstrating a truly preventive effect of this intervention. That SE induces loss of hippocampal neurons is evident from both histological and MRI studies of humans with severe TLE (Cascino, 1998 and Mathern et al., 1998). The control animals undergoing SE in the present study exhibited neuronal loss predominantly in the hippocampal CA3 region ipsilateral to the KA injection, as well as increased GFAP immunoreactivity typical of reactive gliosis, resembling the

pathology in humans and Selleckchem GSK2656157 confirming previous reports (Mouri et al., 2008). This pathology was significantly attenuated, but not eliminated, by transient inhibition of TrkB kinase commencing after SE. Because activation of TrkB signaling would be expected to protect neurons from HIF inhibitor death (Huang and Reichardt, 2003), the reduction in neuronal death after inhibition of TrkB kinase is surprising. One possibility is that the loss of hippocampal neurons in animals undergoing SE followed by inhibition of TrkB kinase is due to injury sustained during SE itself. If so, the greater loss of hippocampal neurons in the control groups may be due both to SE and to the many isolated seizures that ensued over a couple of months prior to death. The fact

that many isolated seizures result in destruction of hippocampal neurons (Kotloski et al., 2002) supports this idea. A diversity of behavioral disorders has been identified in patients with epilepsy with a greater frequency than in other chronic diseases, impairing the quality of life (Torta and Keller, 1999). Anxiety disorders are the most common behavioral conditions Sodium butyrate found in patients with epilepsy (Beyenburg et al., 2005). Animals undergoing SE in the current study exhibited a striking reluctance to enter the lighted compartment in the light-dark emergence test. Based on the innate aversion of rodents to brightly illuminated areas and on the spontaneous exploratory behavior of rodents in response to mild stressors (novel environment and light), the reluctance of mice undergoing SE to enter the lighted compartment is a response thought to reflect anxiety. Notably, this reluctance was eliminated in animals undergoing TrkB kinase inhibition. Thus, enhanced TrkB kinase signaling induced by SE not only results in recurrent seizures, but it also renders the subject vulnerable to expressing anxiety-like behavior.

A similar increase was seen in GPHN FingR-GFP staining between in

A similar increase was seen in GPHN.FingR-GFP staining between induced versus uninduced, consistent with a coordinated upregulation of FingR expression. To quantify the relative fidelity with which GPHN.FingR-GFP-labeled uninduced versus induced cells, we calculated the

ratio of total Gephyrin staining versus GPHN.FingR-GFP staining at individual puncta. We found that the ratio of total Gephyrin staining versus GPHN.FingR-GFP staining was 1.40 ± 0.03 (n = 200 puncta, 10 cells) for uninduced versus 1.47 ± 0.06 (n = 200 puncta, 10 cells) for induced cells. The two ratios are not significantly selleck chemicals llc different (p = 0.15, Wilcoxon), indicating that GPHN.FingR-GFP labeled Gephyrin with similar fidelity in the uninduced versus induced cells, a result that is consistent with the transcriptional regulation system responding to the increase in target with an appropriately graded increase in FingR production. To test whether

the transcriptional regulation system could work for two FingRs simultaneously, we coexpressed PSD95.FingR-GFP and GPHN.FingR-mKate2 for 7 days. Both had independently regulated transcriptional control systems. PSD95.FingR-GFP was fused to the CCR5L zinc finger (Mani Ribociclib et al., 2005), and GPHN.FingR-mKate2was fused to the IL2RG2L zinc finger (Gabriel et al., 2011). PSD95.FingR-GFP and GPHN.FingR-mKate2 each expressed in a distinctly punctate manner with very little background or overlap between the two (Figure 3H), indicating Thymidine kinase that each transcriptional feedback system worked efficiently and independently. To this point our experiments have concentrated on using FingRs to visualize the localization of endogenous proteins at single points in time. However, because FingRs can be visualized in living cells,

it should be possible to use them to observe trafficking of their endogenous target proteins. To visualize trafficking of Gephyrin we used lentivirus to express transciptionally controlled GPHN.FingR-GFP in neurons in culture for 7 days. Time-lapse imaging of these cultures revealed numerous vesicles moving in both directions in the cell body, axons, and dendrites (Figures 3I and 3J). Interestingly, axonal vesicles appeared more elongated and moved at higher velocity than dendritic vesicles, hitting speeds of ∼7 μm.s−1 (Movie S1). Thus, GPHN.FingR-GFP can be used to visualize trafficking of endogenous Gephyrin in addition to its localization. To test whether FingRs label their endogenous targets specifically in cortical neurons in culture, we expressed either transcriptionally controlled PSD95.FingR-GFP or GPHN.FingR-GFP along with siRNA against either PSD-95 or Gephyrin. Cells in which either endogenous PSD-95 or endogenous Gephyrin was knocked down expressed extremely low levels of the corresponding FingR (Figures 4A–4D, 4I–4L, and S3). In contrast, cells expressing either PSD95.FingR or GPHN.

Wheel running tended to attract individuals who are highly motiva

Wheel running tended to attract individuals who are highly motivated to engage in frequent, sustained exercise, which selleck kinase inhibitor reflected a voluntary, active physical and mental state, while treadmill running attracts those that are forced to exercise, which reflects an attitude

towards exercise.41 Only very recently have there been studies demonstrating the sex differences in exercise intervention for drug addiction and rehabilitation. In one such study, Sanchez and colleagues42 found that 10-day wheel running after the formation of rat SA attenuated nicotine-seeking in male rats only under the conditions of access to unlocked wheels. However, access to either locked or unlocked wheels was sufficient to suppress nicotine-seeking during extinction in females. Also 14-day wheel running during abstinence on subsequent

cocaine-seeking of rat’s SA can effectively reduce relapse vulnerability in a dose dependent manner, and this effect differs by sex and estrous cycle.43 Since females perform wheel and treadmill running differently than males, it is important to include the consideration of sex-specific effectiveness of exercise on drug rehabilitation in animal experiments. In addition to wheel and treadmill running, forced swimming has also been used for studies of exercise rehabilitation. Forced swimming exercises could be evaluated for exercise performance, psychological status (anxiety and stress), cognition (learning and memory), etc. 44 and 45 It also showed the same effectiveness as displayed in voluntary wheel running in alcohol conditioned place aversion (CPA), 46 and 47 suggesting that forced swimming may be one mode for exercise intervention for drug addiction. Again, compared to male rats, female rats were more active in water 48 and swam faster in speed with less sign of fatigue. 49 and 50 Exercises attenuate drug-seeking behaviors during drug initiation, escalation, extinction, abstinence, and relapse.51 and 52 It is crucial to decrease the susceptibility (preventive effect) at an early stage of drug addiction and reduce the

drug craving (therapeutic effect) at later stages in order to prevent relapse. L-NAME HCl As most of animal studies in biology research show, researches about exercise as a means of prevention on drug abuse are limited by investigating male animals only,53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67 and 68 with a few studies on female animals,69, 70, 71, 72, 73 and 74 while the others did not specify the gender.75 and 76 In regard to the sex differences as shown in Table 1, the results of these studies have been inconsistent. One study found that chronic forced treadmill exercise for 6 weeks induced reduction of drug craving behavior in adolescent female and male rats, but only male rats showed inhibited CPP.

Death of astrocytes shortly after their generation and the elevat

Death of astrocytes shortly after their generation and the elevated expression of hbegf mRNA in endothelial cells compared to astrocytes ( Cahoy et al., 2008 and Daneman et al., 2010) support the hypothesis that astrocytes may require vascular cell-derived trophic support. MD-astrocytes show remarkable proliferative ability and can be passaged repeatedly over many months.

In contrast, most astrocyte proliferation in vivo is largely complete by P14 (Skoff and Knapp, 1991). To directly compare the proliferative capacities of MD and IP-astrocytes P7, we plated dissociated single cells at low density in a defined, serum-free SCH772984 media containing HBEGF and counted clones at 1, 3, and 7DIV (Figures S1Q–S1S). MD-astrocytes displayed a much higher proliferative capacity, 75% of them dividing once every 1.4 days by 7DIV. In contrast, 71% of IP-astrocytes divided less than once every 3 days (Figure S1S). Thus IP-astrocytes have a more modest ability to divide compared with MD-astrocytes, this is more in line with what is expected in vivo (Skoff and Knapp 1991). Using gene profiling, we determined if gene expression of cultured IP-astrocytes was more similar to that of acutely purified astrocytes, compared to MD-astrocytes. Total RNA was isolated from acutely purified astrocytes from P1 and P7 rat brains (IP-astrocytes P1 and

P7) and from acutely isolated cells cultured for 7DIV with HBEGF (IP-astrocytes P1 and P7 7DIV, respectively) and from MD-astrocytes (McCarthy very and de Vellis, 1980). RT-PCR with cell-type specific primers was used to assess the purity of the isolated PD-0332991 supplier RNA. We used GFAP, brunol4,

MBP, occludin, CX3CR1 as mentioned above, as well as chondroitin proteoglycan sulfate 4 (CSPG4) for OPCs and pericytes. MD-astrocytes consistently had some neuron contamination because of the high percentage of contaminating neural stem cells ( Hildebrand et al., 1997; Figure 4A). This was not observed in IP-astrocyte cultures. IP-astrocytes P1 and P7 7DIV cells had an expression profile resembling their acutely isolated counterparts, where only 118 and 54 genes respectively differed significantly (p < 0.05). In contrast, MD-astrocyte expression profiles were significantly different from that of acutely purified cells (Table 1; Figure 4B). With a very stringent statistical test (moderated t test) and posttest (Bonferroni correction) to identify the most significant changes, we found that 547 and 729 genes were significantly different (p < 0.05) between acute IP-astrocytes P1 or P7 cells and MD-astrocytes, respectively. These results strongly suggest that by gene expression, cultured IP-astrocytes are more similar to cortical astrocytes in vivo. Only 54 genes out of over 31,000 genes differed significantly between acute IP-astrocytes P7 and IP-astrocytes P7 7DIV (p < 0.05).

Even the simplified two-link structure of the limbs during constr

Even the simplified two-link structure of the limbs during constrained reaching exhibits complex nonlinear dynamics (Hollerbach and MK-1775 molecular weight Flash, 1982). These nonlinearities within the motor system provide a major challenge for the sensorimotor control system, even if none of the other problems existed; however, the inclusion of these other problems makes the task even more challenging. Progress has been made into the computations that the sensorimotor system can perform to alleviate these problems. The remainder of the review will examine these computations

and how they relate to the five problems of sensorimotor control we have highlighted. Bayesian decision theory is a framework for understanding how the nervous system performs

optimal estimation and control in an uncertain world. It is composed of two components, Bayesian statistics and decision theory. Bayesian statistics involves the use of probabilistic reasoning to make inferences based on uncertain data, both combining uncertain sensory estimates with prior beliefs and combining information from multiple sensory modalities together, in order to produce optimal estimates. We use the term Bayesian inference in this review to refer to probabilistic reasoning and not simply to the application of Bayes’ rule (see below). Based on these inferences, decision theory is used to determine the optimal actions to take given task objectives. Different sensory modalities can often sample the same information about the state of our body (e.g., proprioceptive and visual location of the hand) or the state of the external world (e.g., auditory and Resminostat visual location of a bird). When these different modalities are experimentally

put in conflict, for example by mismatching the vision and sound of a person speaking, the percept corresponds to something intermediate between the percept of each modality alone (McGurk and MacDonald, 1976). Recent work has developed and tested the computational framework that underlies such multisensory integration. Even for normal sensory inputs, our sensory apparatus is variable and can have biases. Therefore, the estimates from different modalities are unlikely to be the same. Within the Bayesian framework, we can ask what is the most probable state of the world that gave rise to the multiple sensory inputs. Such a Bayesian model predicts that a scalar estimate from two different modalities, such as the visual and haptic width of a held object, should be weighted and averaged to produce an optimal estimate. Critically, the weighting of each modality should depend on its reliability (or the inverse of its variability due to noise), with the more reliable modality contributing more to the final estimate. Such a model of multisensory integration is supported by experimental studies of size estimation from visual and haptic cues (Ernst and Banks, 2002), location from visual and auditory cues (Körding et al.

Signal-to-noise ratios in the autism group were positively correl

Signal-to-noise ratios in the autism group were positively correlated with IQ scores (Figure 5, middle) and negatively correlated with autism symptom severity as assessed by the ADOS test (Figure 5, bottom) in all three experiments. However, only the correlation between signal-to-noise and IQ in the visual experiment was statistically significant. There was no evidence of signal-to-noise differences across subject groups in subcortical nuclei (Figure 6). We manually identified two subcortical ROIs—the lateral geniculate nucleus (LGN) and the medial geniculate nucleus (MGN)—using the average activation maps across all subjects in each group (Figure 1). Analyses of the responses in the two ROIs did not

reveal any significant differences between groups in any of the measures (Figures find more 6A–6C). Both subject groups exhibited robust motor responses when indicating letter repeats via a button press (Figure 7A). We used these responses to identify three motor ROIs (Figure S2): left primary motor cortex (Mot), right and left anterior intraparietal sulcus (aIPS), and

right and left ventral premotor cortex (vPM). Response buy Sirolimus amplitude, variability, and signal-to-noise were statistically indistinguishable across the two groups across all three ROIs (Figure 7). In this analysis, we combined trials across all three experiments because the task at fixation was identical. Individuals with autism were significantly slower and less accurate in detecting letter repeats than controls. This raised a concern

that the higher trial-by-trial sensory response variability reported in the autism group might be a consequence of the performance difference across groups. To address this issue, we excluded eight scans with the poorest performance these in the autism group and four scans with the best performance in the control group, so as to match mean accuracy and reaction times across groups (Figures 8A and 8B). Cortical response signal-to-noise ratios remained significantly smaller in the autism group (Figure 8C) even when behavioral performance was statistically indistinguishable across groups. The behavioral analyses also revealed that trial-by-trial variability in reaction times was larger in individuals with autism when comparing across all scans and when considering only the subset of scans for which mean accuracy and reaction times were matched across groups (Figure S6). We performed several control analyses to ensure that larger trial-by-trial fMRI variability in the autism group was not caused by more variable head motion, heart rate, respiration, or eye fixation during the experiments. The variability of all six head motion estimates, derived during 3D motion correction, was statistically indistinguishable across groups as was the mean frame-by-frame displacement (Figures S7A and S7B). Furthermore, we reanalyzed the fMRI responses after removing head motion parameters using orthogonal projection (Fox et al.

Compared to controls, conditional Erbb4 mutants exhibited a marke

Compared to controls, conditional Erbb4 mutants exhibited a marked increased in oscillatory power in the resting-state ( Figures 5B and 5C). Frequent bursts of high-frequency oscillations were observed in the DG, which often correlated with simultaneous increases in oscillatory power in the CA1 region and, occasionally, the overlying neocortex ( Figures 5B and 5C). Consistently, DG-CA1 coherence increased significantly in conditional Erbb4 mutants, especially at relatively high frequencies ( Figure 5D). ERK inhibitor Closer inspection of these resting-state recordings revealed the presence of spontaneous and fully developed field population spikes in the DG closely resembling field potentials

evoked by perforant path stimulation ( Figure 5E). This finding strongly suggests the presence of synchronous activity bursts already in the entorhinal cortex, a region in which we also found deficits of interneuron synapses in conditional Erbb4 mutant mice BIBW2992 price ( Figure 2I). To further investigate neuronal synchrony in the hippocampus, we measured the input-output function in the trisynaptic circuit (DG → CA3 → CA1) by correlating the excitatory postsynaptic potential (EPSP) in the DG in response to perforant path stimulation (∼2 ms delay) and the population spikes recorded in CA1 (∼8 ms

delay). We observed that the polysynaptic propagation of activity in the hippocampal formation is largely facilitated in conditional Erbb4 mutant mice ( Figures 5E, arrows, and 5F). These observations were replicated in ketamine-anesthetized conditional Erbb4 mutant

mice ( Figures S5A–S5E), which revealed that the enhanced oscillatory power observed in mice lacking ErbB4 was not directly related to a particular anesthetic compound. In some cases, however, we observed that ketamine led to epileptic hypersynchrony in conditional Erbb4 mutants (n = 3 out of six mice, data not shown), a phenomenon that was never observed in ketamine-anesthetized controls or in urethane-anesthetized control or Erbb4 mutant mice. As ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist, these results suggested also that NMDA receptor blockage enhances the physiological disturbances caused by the loss of ErbB4 in fast-spiking interneurons. We observed a sustained elevation in relative power for all frequencies above 4 Hz in the CA1 area of conditional Erbb4 mutants compared to controls ( Figure 5G). This increase was significant for the theta, alpha, beta, and gamma bands ( Figures 5H) and was particularly perceptible with wavelet analyses ( Figures 5I and 5J). The dramatic alteration of hippocampal rhythms was also evident in the CA1 area of ketamine-anesthetized Erbb4 mutants ( Figures S5F–S5I) and in the DG independently of the anesthetic compound used in the experiments ( Figure S6).

We also divide the trials into two categories: a correct trial is

We also divide the trials into two categories: a correct trial is one in which the two cards revealed a matching pair and an incorrect trial indicates that the subject chose nonmatching cards. After the recording session, the local field potential data were extracted for each mouse click on a card, which coincided HA-1077 price with the presentation of the image stimulus. The segments of data were approximately four seconds long, centered on

each click (±2 s). This length was chosen to avoid edge effects in the time range of interest, which was ±1 s around the stimulus presentation. After resampling at 2 kHz, we removed the mean of each data segment during the presentation of the stimulus. No other filtering was done on the data. We utilized the free WaveLab toolbox for MATLAB (Donoho et al., 2005) to perform the wavelet analysis. More specifically, we used the “CWT_Wavelab” function to do a continuous wavelet transform. We chose a complex Morlet wavelet with the following time domain representation: ψ(t)=e−12t2(eiω0t−e−12ω02).Or equivalently in the Fourier Cobimetinib price domain, ψˆ(ω)=e−12(ω−ω0)2−e−12(ω2+ω02),with ω0=5ω0=5 representing the number of cycles in the wavelet. For the WaveLab function, we chose parameters nvoice = 10, scale = 4, and oct = 6. These settings allowed us to analyze 70 frequencies,

ranging from 0.87 Hz to 103.97 Hz (the frequencies varied by 0.1 from −0.2 to 6.7 on a logarithmic scale of base 2). The exact length of each data segment was 8,192 data points (4.096 s at 2 kHz) to fulfill the requirement of an input signal with dyadic length. The result of convolving the Morlet wavelet with our LFP data was a complex signal Z(t). We used this to calculate both the instantaneous amplitude A(t)=Re[Z(t)]2+Im[Z(t)]2and the instantaneous phase φ(t)=arctan(Im[Z(t)]Re[Z(t)]). These equations are equivalent to the “abs” and “angle” functions

in MATLAB. The phase spanned the range [−π, π] with zero being the peak of the oscillation. As a measure of the baseline activity in each data set, we calculated the average instantaneous amplitude A¯ over 1,000 randomly selected segments of data. Then, using the standard deviation of amplitude σAσA over the 1,000 segments and Rutecarpine the number of trials n, we were able to represent the amplitude as a Z score based on the statistics of the population: A˜(t)=A(t)−A¯σAn. The goal of single trial classification is to determine how accurately we can divide single trials of LFP data into two categories based on whether they were triggered on a correct response (matching cards) or an incorrect response (nonmatching cards). We begin by using the first data set (ten puzzles with a total of 80 correct trials) to calculate the classifier. Given this limited data set, we chose a linear classifier. For all LFP responses in the data set, we determine the mean of the correct trials a¯ and the mean of the incorrect trials b¯, and we define the classifier to be b¯−a¯.

Therefore, we stimulated cortical neurons with BDNF at 15 days in

Therefore, we stimulated cortical neurons with BDNF at 15 days in vitro (DIV) (Figure S2A), a stage when FMRP, CYFIP1, and eIF4E are highly expressed and neurons are mature (Figure S2A). We stimulated neurons with BDNF, which induces translation (Aakalu et al., 2001, Schratt et al., 2004 and Takei et al., 2004) and actin remodeling (Bramham, 2008), and followed the subsequent changes in the colocalization of CYFIP1 with eIF4E or NCKAP1. Stimulation by BDNF significantly reduced the degree of CYFIP1-eIF4E colocalization, and concomitantly increased the number of CYFIP1-NCKAP1 puncta, suggesting that CYFIP1 distribution changes between these complexes upon TrkB receptor

activation (Figures 2A and S2B). The magnitude of these changes is similar to those observed with manipulations that alter interactions of eIF4E with canonical Fluorouracil price eIF4E-BPs (Costa-Mattioli et al., 2009, Richter and Klann, 2009 and Sonenberg and Hinnebusch, 2009). These changes were observed 15 min after BDNF stimulation (Figure S2C). Only a very small proportion of CYFIP1 remained not engaged

within these two complexes (∼15% according to the colocalization data). Consistently, blue native PAGE (BN-PAGE) revealed that the majority, if not all, of CYFIP1 is part of CX5461 high molecular weight complexes (Figure S2D). Based on these data, we infer that a “free” CYFIP1 pool is minor. We then aimed at identifying the factors regulating this equilibrium. A candidate is Rac1, because in its active form (GTP-Rac1), it interacts with CYFIP1 (Kobayashi et al., 1998) and favors WRC activation (Chen et al., 2010, Eden et al., 2002, Schenck et al., 2003 and Steffen over et al., 2004). To test this hypothesis, we used NSC23766,

a specific inhibitor of Rac1 activation (Gao et al., 2004) (Figure S2E). Addition of NSC23766 before BDNF stimulation prevented the redistribution of CYFIP1 (Figure 2A), indicating that active Rac1 is needed for the effect of BDNF on the CYFIP1 complexes. To further monitor the dynamics of CYFIP1 redistribution, we quantified the changes in fluorescence of EYFP-CYFIP1, Cerulean-NCKAP1, and eIF4E-mCherry in spines of BDNF-stimulated primary neurons over time (Figure S3). We observed that the ratio of Cerulean-NCKAP1 over EYFP-CYFIP1 steadily increases, indicating a build-up of WRC (Figure S3C). CYFIP1 redistribution between eIF4E- and NCKAP1-containing complexes was further corroborated by biochemical evidence in isolated synaptoneurosomes: BDNF stimulation increased the amount of CYFIP1 coprecipitating with NCKAP1, and conversely reduced its binding to eIF4E; the Rac1 inhibitor was able to prevent the CYFIP1 redistribution (Figure 2B). To investigate whether active Rac1 directly changes the ability of CYFIP1 to bind eIF4E, we used GTP-Rac1 as exogenous competitor in m7GTP chromatography on cortical lysates.

This means that the antibodies induced by Qβ-IL-5 and Qβ-Eot are

This means that the antibodies induced by Qβ-IL-5 and Qβ-Eot are neutralizing antibodies and they can block the bioactivity of the corresponding cytokines in vivo. We also noticed that low numbers of eosinophils in lung tissue were still present. The pathological role of these eosinophils should be further investigated. In order to completely block the eosinophilia in the lung, a combination of vaccines AUY-922 research buy against eotaxin, eotaxin-2 and IL-5 may be beneficial.

The reduction of eosinophilia may not only have a role in the abrogation of acute processes but also in events further down stream such as repair and remodelling caused by chronic eosinophilic inflammation. As discussed above, a recent study in man has shown that even modest eosinophil depletion by anti–IL-5 was associated with significant reductions in tenascin and lumican deposition in the bronchial reticular basement membrane, two markers of airway remodelling [17]. Therefore, combined vaccination against IL-5 and eotaxin using VLP-based vaccines which induce high and lasting auto-antibody Proteasome activity titers against the corresponding molecules, abrogating eosinophilia, may prevent lung remodelling. To our knowledge, this is the first report which describes active vaccination simultaneously targeting more than one self-antigen.

The result shown here is of potential consequence for our continuously aging society. According to the World Health Organization, in the industrialized world, as many as 25% of 65–69-year olds and 50% of 80–84-year

olds are affected by two or more chronic health conditions. Combined vaccination against more than one self-antigen opens the possibility to target chronic diseases in which multiple factors are involved. these Moreover, this strategy could be used to target more than one disease at the same time. This project was supported by Kommission for Technologie und Innovation (project 6204.2 KTS-LS). “
“Malaria is the most devastating parasitic disease affecting humans. Each year there are 300–500 million new infections and greater than one million deaths [1]. Antibodies against blood stage antigens are thought to be important in immunity to malaria, since passive transfer of purified immunoglobulin from individuals with lifelong exposure to endemic malaria results in a marked decrease in parasitemia and resolution of symptoms in the recipients [2]. Parasite proteins expressed on the surface of infected erythrocytes and merozoites and in merozoite apical organelles, including the merozoite surface protein 1 (MSP1) and the apical membrane antigen 1 (AMA1), are considered high priority antigens for blood stage vaccine inhibitors development [3]. AMA1 [reviewed in [4]] is a 72 kDa protein that is located in the apical microneme organelles and then on the surface of the merozoite [5] and is involved in erythrocyte invasion [6].