However, this pays little heed to the large number of repetition enhancement effects observed under similar conditions. In this review, we identify several cognitive variables biasing repetition effects in the BOLD response towards enhancement instead of suppression. These variables are stimulus recognition, learning, attention, expectation and explicit memory. We also evaluate which models can account for these repetition effects and come to the conclusion that there is no one single model that is able to embrace all repetition enhancement effects. Accumulation, novel network formation as well

as predictive coding ML323 models can all explain subsets of repetition enhancement effects. (C) 2012 Elsevier Ltd. All rights reserved.”
“The promiscuous presentation of epitopes by similar Belnacasan mouse HLA class I alleles holds promise for a universal T-cell-based HIV-1 vaccine. However, in some instances, cytotoxic T lymphocytes (CTL) restricted by HLA alleles with similar or identical binding motifs are known to target epitopes at different frequencies, with different functional avidities and with different apparent clinical outcomes. Such differences may be illuminated by the association of similar HLA alleles with distinctive escape pathways. Using a novel computational method featuring phylogenetically corrected odds ratios, we systematically analyzed

differential patterns of immune escape across all optimally defined epitopes in Gag, Pol, and Nef in 2,126 HIV-1 clade C-infected adults. Overall, we identified 301 polymorphisms in 90 epitopes associated with HLA alleles belonging to shared supertypes. We detected differential escape in 37 of 38 epitopes restricted by more than one allele, which included 278 A-769662 nmr instances of differential

escape at the polymorphism level. The majority (66 to 97%) of these resulted from the selection of unique HLA-specific polymorphisms rather than differential epitope targeting rates, as confirmed by gamma interferon (IFN-gamma) enzyme-linked immunosorbent spot assay (ELISPOT) data. Discordant associations between HLA alleles and viral load were frequently observed between allele pairs that selected for differential escape. Furthermore, the total number of associated polymorphisms strongly correlated with average viral load. These studies confirm that differential escape is a widespread phenomenon and may be the norm when two alleles present the same epitope. Given the clinical correlates of immune escape, such heterogeneity suggests that certain epitopes will lead to discordant outcomes if applied universally in a vaccine.”
“The cingulum is a prominent white matter tract that supports Prefrontal, parietal, and temporal lobe interactions. Despite being composed of both short and long association fibres, many MRI-based reconstructions (tractography) of the cingulum depict an essentially uniform tract that almost encircles the corpus callosum.

“
“PRA1 domain family, member 2 (PRAF2) is a novel 19-kDa protein with a prenylated Rab acceptor 1 (PRAI) motif and four transmembrane domains. Our previous studies revealed EPZ015666 that PRAF2 is highly expressed in the brain and serves as a candidate prognostic marker in neuroblastoma (NB). PRAF2 is related to proteins PRAF1 (PRA1, prenylin, Yip3) and PRAF3 (GTRAP3-18, JWA, Ar16-IP5), both of which are enriched in the brain and implicated in cellular transport and endo/exocytic vesicle trafficking. However, the function

for PRAF2 remains unknown. In this study, we analyzed the distribution and localization of PRAF2 in the mature human brain using two new antibodies specific for the protein. Analysis by immunohistochemistry revealed that in the human cerebellum, the PRAF2 protein was strongly expressed in Purkinje cells and, more moderately, in cells of the molecular and the granular layers.

In the cerebral cortex, hippocampus, and lateral ventricles, PRAF2 protein was detected in neuronal cells, but not in non-neuronal cells. Intriguingly, immunoblot analysis revealed that PRAF2 is enriched in synaptic vesicles (SVs) prepared from rat brains. The expression of PRAF2 in specific regions of the brain including SVs suggest an important physiological function for this novel protein, see more possibly by participating in multiple aspects of SV maturation, transport, and signal transmission. (C) 2008 Elsevier Ireland Ltd. All rights reserved.”
“Purpose: We determined whether intravesical. instillation of antifibrinolytic agents could improve the antitumor effect Torin 1 ic50 of bacillus Calmette-Guerin. We also investigated the impact of these antifibrinolytic agents

on the dose of bacillus Calmette-Guerin required for a therapeutic effect.

Materials and Methods: In this randomized, prospective, double-blind, controlled pilot study 257 patients with superficial bladder cancer were randomized into groups A through E. They received 100 to 120 mg intravesical bacillus Calmette-Guerin plus 100 mg para-aminomethylbenzoic acid, 50 to 60 mg bacillus Calmette-Guerin plus 100 mg para-aminomethylbenzoic acid, 100 to 120 mg bacillus Calmette-Guerin plus 2.0 gm epsilon aminocaproic acid, 50 to 60 mg bacillus Calmette-Guerin plus 2.0 gm epsilon aminocaproic acid and 100 to 120 mg bacillus Calmette-Guerin alone, respectively. Prothrombin time and activated partial thromboplastin time of each patient were determined at 2 hours after instillation, and adverse events were evaluated. Tumor recurrence was assessed every 3 months postoperatively by cystoscopy. Median followup was 26.0, 25.0, 24.5, 25.0 and 25.5 months, respectively.

Method: Spontaneous baroreflex sensitivity (sBRS) was estimated in 45 patients with at least a severe carotid stenosis (70%-99%). sBRS calculation was performed noninvasively, with the spontaneous sequence method, based on indirectly estimated central blood pressures from radial recordings. This method failed in three patients due to poor-quality recordings, and

eventually 42 patients were evaluated. After carotid duplex examination, carotid plaque echogenicity was graded from 1 to 4 according to Gray-Weale classification and the patients were divided into two groups: the echolucent group (grades 1 and 2) and the echogenic group (grades 3 and 4).

Results: Sixteen patients (38%) and 26 patients (62%) were included in the echolucent and selleck echogenic group, respectively. Diabetes mellitus was observed more frequently among echolucent plaques (chi(2) Capmatinib in vivo = 8.0; P < .004), while those plaques were also more commonly symptomatic compared with echogenic atheromas (chi(2) = 8.5; P < .003). Systolic arterial pressure, diastolic arterial pressure, and heart rate were similar in the two groups. Nevertheless, the mean value of baroreflex sensitivity was found to be significantly lower in the echogenic group (2.96 ms/mm Hg) compared with the echolucent one (5.0 ms/mm Hg), (F[1,

42] = 10.1; P < .003).

Conclusions:These findings suggest that echogenic plaques are associated with reduced baroreflex function compared with echolucent ones. Further investigation is warranted to define whether such an sBRS impairment could be responsible for cardiovascular morbidity associated with echogenic plaques. (J Vasc Surg 2011;54:93-99.)”
“Chronic Selumetinib price caffeine consumption has been inversely associated with the risk of developing dementia and Alzheimer’s disease.

Here we assessed whether chronic caffeine treatment prevents the behavioral and cognitive decline that male Wistar rats experience from young (approximate to 3 months) to middle age (approximate to 10 months). When animals were young they were evaluated at weekly intervals in three tests: motor activity habituation in the open field (30-min sessions at the same time on consecutive days), continuous spontaneous alternation in the Y-maze (8 min), and elevated plus-maze (5 min). Afterward, rats from the same litter were randomly assigned either to a caffeine-treated group (n=13) or a control group (n=11), which received only tap water. Caffeine treatment (5 mg/kg/day) began when animals were approximate to 4 months old, and lasted for 6 months. Behavioral tests were repeated from day 14 to day 28 after caffeine withdrawal, a time period that is far in excess for the full excretion of a caffeine dose in this species. Thirty days after caffeine discontinuation brains were processed for Golgi-Cox staining.

No previous study used this design to examine the same dimensions. The best-fitting model included additive genetic and nonshared environmental components, each accounting for about half of total variance in the symptoms. Genetic influences on the different symptoms overlapped considerably (r(g)=0.81 to 0.99). Phenotypic correlations of psychotic symptoms and of psychotic with obsessive symptoms were high (r=0.61 to 0.76), with 53% to

69% explained by shared genetic effects. This study shows substantial genetic influence on psychotic and obsessive symptoms, and indicates that their co-occurrence may be due to genetic factors to a greater extent than to environmental effects. These results encourage the search

for genetic and environmental factors underlying the covariance Buparlisib between different psychotic traits as well as between psychotic and obsessive traits. (C) 2010 Elsevier Ireland Ltd. All rights reserved.”
“The object of this study was to develop a reverse transcription-loop-mediated isothermal amplification (RT-LAMP) assay for detecting hepatitis D virus (HDV) genotype 1. With an alignment analysis, a highly conserved sequence (nt 8201020) was chosen as a suitable target to design LAMP primers. The optimal condition of RT-LAMP was a 25-l reaction volume, which consists of the following components: 1 center dot 6moll1 each of FIP and BIP, 0 center dot 2moll1 each of F3 and B3, 1 center dot 5moll1 dNTPs, 4mmoll1 MgSO4, 8U Bst DNA polymerase, 2U Selleck Blasticidin S M-MLV and 2l extracted RNA sample. The amplification reaction was carried out at 65 degrees C for 50min. Compared with conventional qualitative or quantitative real-time reverse transcription polymerase chain reaction, the results of RT-LAMP indicated a 1000-fold increase in sensitivity for detecting HDV. There was no cross-reaction for the RT-LAMP method between HDV 1 and HIV, HAV, HBV, HCV and HEV.”
“This study examined the relationship between negative symptoms and social see more cognition in individuals with psychosis. Although negative symptoms were associated with social cognition, stereotyped

thinking, which is cognitive in nature, emerged as the most significant predictor, suggesting that cognition rather than symptoms may have a greater impact on social cognition. (C) 2011 Elsevier Ireland Ltd. All rights reserved.”
“Objectives: Alveolar-pleural fistulas causing persistent air leaks are conditions associated with prolonged hospital courses, high morbidity, and possibly increased mortality. Intrabronchial valves serve as a noninvasive therapeutic option for the closure of alveolar-pleural fistulas.

Methods: The present review describes a brief history of, and indications for, the placement of intrabronchial valves in patients with persistent air leaks. The essential steps necessary for placement are air leak isolation, airway sizing, and valve deployment.

“
“Background. Alcohol consumption is influenced by specific genetic risk factors for alcohol use disorders (AUDs), non-specific genetic risk factors for externalizing behaviors and various environmental experiences. We have limited knowledge of how these risk factors inter-relate through development.

Method. Retrospective assessments in 1796 adult male twins using a life history calendar of key environmental exposures and alcohol consumption from early adolescence to mid-adulthood.

Analysis by linear mixed models.

Results. The importance of non-specific genetic risk factors on maximal alcohol consumption rose rapidly in early to mid-adolescence, peaked at ages 15-17 years and then declined slowly. Alcohol-specific

genetic risk factors increased slowly in influence this website through mid-adulthood. We detected robust evidence for environmental moderation of genetic effects on alcohol consumption that was more pronounced in early and mid-adolescence than in later periods. Alcohol availability, peer deviance and low prosocial behaviors showing the strongest moderation effects. More interactions with environmental risk factors were seen for the non-specific externalizing disorder risk than for specific genetic risk for AUDs.

Conclusions. The impact of specific and non-specific genetic influences on alcohol consumption have different development trajectories. Genetic effects

Nirogacestat cost on alcohol use are more pronounced when social constraints are minimized (e. g. low prosocial behaviors or parental monitoring) or when the environment permits easy access to alcohol and/or encourages its use (e. g. high alcohol availability or peer deviance). Gene-environment interactions influencing alcohol intake may be more robust at younger ages, indicating greater plasticity of genetic influences early in the development of drinking patterns.”
“We sought to understand the association between aggregate health burdenuchronic conditions, functionally limiting health problems and mental C188-9 clinical trial well-beinguand the likelihood of hospitalization among older persons post hip replacement surgery.

Eight hundred and twenty-eight Medicare recipients from three U.S. states completed a questionnaire 3 years postsurgery. Using administrative data (Medicare Provider Analysis and Review), participants were prospectively followed for 12 months postquestionnaire to capture hospitalizations. Using logistic regression, demographic, socioeconomic, and behavioral characteristics and medical comorbidities were considered as predictors. Subsequently, musculoskeletal (MSK) functional and geriatric problems were added as predictors, then mental well-being and activity limitations.

98 (1.13-3.45) and 1.92 (1.07-3.44), respectively). The A-1438G and 5-HTTLPR polymorphisms also interacted in distinguishing alcohol from heroin dependent patients (Wald (df) = 10.21 (4), p = 0.037). The association of -1438A/G with alcohol dependence

was especially pronounced in the presence of 5-HTTLPR S/S, less evident Tideglusib in vivo with 5-HTTLPR L/S and not present with 5-HTTLPR L/L. SCL6A4 polymorphism haplotypes were similarly distributed in all three groups.

Conclusions: Our data do not support a role of serotonergic polymorphisms in alcohol dependence but suggest a differential genetic background to alcohol and heroin dependence. (C) 2009 Elsevier Inc. All rights reserved.”
“Alcoholism (ALC) and HIV-1 infection (HIV) each affects emotional and attentional processes and integrity learn more of brain white matter fibers likely contributing to functional compromise. The highly prevalent ALC+HIV comorbidity may exacerbate compromise. We used diffusion tensor imaging (DTI) and an emotional Stroop Match-to-Sample task in 19 ALC, 16 HIV, 15 ALC+HIV, and 15 control participants

to investigate whether disruption of fiber system integrity accounts for compromised attentional and emotional processing. The task required matching a cue color to that of an emotional word with faces appearing between the color cue and the Stroop word in half of the trials. Nonmatched cue-word color pairs assessed selective attention, and face-word pairs assessed emotion. Relative to controls, DTI-based fiber tracking revealed lower inferior longitudinal fasciculus (ilf) integrity in HIV and ALC+HIV

and lower uncinate fasciculus (uf) integrity in all three patient groups. Controls exhibited Stroop effects to positive face-word emotion, and greater interference was related to greater callosal, cingulum and ilf integrity. By contrast, HIV showed greater interference from negative Stroop words during color-nonmatch trials, correlating with greater uf compromise. For face trials, ALC and ALC+HIV showed greater Stroop-word interference, correlating with lower cingulate and callosal integrity. Thus, in HIV, conflict resolution was diminished when challenging conditions usurped resources needed to manage interference from negative PD0332991 mouse emotion and to disengage attention from wrongly cued colors (nonmatch). In ALC and ALC+HIV, poorer callosal integrity was related to enhanced emotional interference suggesting curtailed interhemispheric exchange needed between preferentially right-hemispheric emotion and left-hemispheric Stroop-word functions. (C) 2012 Elsevier Ltd. All rights reserved.”
“Herpesvirus proteins pUL34 and pUL31 form a complex at the inner nuclear membrane (INM) which is necessary for efficient nuclear egress. Pseudorabies virus (PrV) pUL34 is a type II membrane protein of 262 amino acids (aa).

However, these CTLs select for the reverse transcriptase (RT) I135X escape mutation, which may be accumulating in circulating HIV-1 sequences. We investigated the selection of the I135X mutation by CTLs specific for the same epitope but restricted by HLA-B*52:01. We found that Pol283-8-specific, HLA-B*52:01-restricted CTLs were elicited predominantly in chronically HIV-1-infected individuals. These CTLs had a strong check details ability to suppress the replication of wild-type HIV-1, though this ability was weaker than that of HLA-B*51:01-restricted CTLs. The crystal structure of the

HLA-B*52:01-Pol283-8 peptide complex provided clear evidence that HLA-B*52:01 presents the peptide similarly to HLA-B*51:01, ensuring the cross-presentation of this epitope by both alleles. Population level analyses revealed a strong association of HLA-B*51:01 with the I135T mutant and a relatively weaker association of HLA-B*52:01 with several I135X mutants in both Japanese and predominantly Caucasian cohorts. An in vitro viral suppression assay revealed that the HLA-B*52:01-restricted NU7441 chemical structure CTLs failed to suppress the replication of the I135X mutant viruses,

indicating the selection of these mutants by the CTLs. These results suggest that the different pattern of I135X mutant selection may have resulted from the difference between these two CTLs in the ability to suppress HIV-1 replication.”
“Background. Relatives of schizophrenia patients demonstrate abnormalities in prefrontal cortical activation during executive processing as measured by functional neuroimaging, albeit not consistently. A meta-analysis was conducted PS341 to determine whether reliable

patterns of brain hypo- and hyperactivity, especially in the middle frontal region, were present in the relatives of patients.

Method. Seventeen studies, containing 18 samples of relatives and controls, were included in this meta-analysis. Studies were included if relatives of schizophrenia patients were compared to controls, an executive processing task was used, and standard space coordinates were reported for the functional activations. Activation likelihood estimation (ALE) was implemented to find convergence across functional neuroimaging experiment coordinates. A separate analysis was conducted to assess the potential impact of a priori hypothesis testing used in region-of-interest (ROI) approaches on the meta-analysis results.

Results. Relatives demonstrated hypo- and hyperactivity in statistically overlapping right middle frontal regions [Brodmann area (BA) 9/10]. Use of an ROI analysis that a priori focused on prefrontal regions resulted in more findings of reduced activity in the middle frontal region.

Conclusions. The cortical regions identified by this meta-analysis could potentially serve as intermediate biological markers in the search for candidate genes for schizophrenia.

Following optimization of

the assay protocols see more and using the MIC results as a reference standard, the absorbance-read MIS assay, the fluorescence-read CTB assay and the absorbance-read CTB (CTB(abs)) assay demonstrated similar high sensitivities (97%, 99% and 98%, respectively), specificities (100%, 98% and 99%, respectively), accuracy measures (0.99, 0.98 and 0.98, respectively), precision measures (1.00, 0.98 and 0.99, respectively) and Cohen kappa agreement indices (0.97, 0.97 and 0.96, respectively) for detecting CPE in cell cultures. Due to its performance, cost effectiveness and ease of use, the CTBabs assay was selected for further evaluation of its ability to detect virus neutralization and to screen antiviral compounds. The CTBabs assay had 99% sensitivity and 100% specificity for the detection of neutralizing antibodies in sera from cattle infected

with FMDV and in sera from unvaccinated, uninfected cattle and resulted in a mean Z’-factor of 0.85 for antiviral compound test plates. The CTB(abs) assay is now used routinely in the Belgian FMD reference laboratory for serological testing and high-throughput antiviral compound screening. (C) 2011 Elsevier B.V. All rights reserved.”
“Recent studies have indicated that bone marrow stromal cells (BMSCs) have significant tropism towards glioma which makes them play an important role in carrying genes/drugs to inhibit the growth of glioma as cell vehicles. But BMSCs may differentiate into neural cells under entocranial environment and few researches support the idea that neurally differentiated bone marrow stromal cells (N-D-BMSCs) still hold the capacity of migrating to the tumor sites. The aim of our study selleck compound was to investigate the tropism of N-D-BMSCs towards C6 glioma. In vitro migration assay was employed by transwell co-culture system and Student’s t-test analysis indicated that N-D-BMSCs had the significant tropism towards C6 glioma-conditioned medium (GCM) (P < 0.01). Furthermore, the vascular endothelial growth click here factor (VEGF) bioactivity of the C6

GCM was neutralized by the anti-rat VEGF antibody and our data suggested that the VEGF from C6 GCM hold chemoattraction for N-D-BMSCs and some other cytokines from the C6 GCM may be responsible for the chemoattraction for N-D-BMSCs. In vivo migration assay was carried out with cells transplantation and one way ANOVA analysis indicated that the tropism of N-D-BMSCs towards C6 glioma sites presented time variation (P-value = 2.9E-20). Moreover, multiple comparisons for the time variables with the Student’s t-test and the results suggested that the migration capacity of N-D-BMSCs towards C6 glioma sites reach the peak on the 7th day after transplantation. These results demonstrate that N-D-BMSCs as well as BMSCs have significant tropism towards C6 glioma. Published by Elsevier Ireland Ltd.”
“Coxsackievirus A16 (CVA16), together with enterovirus type 71 (EV71), is responsible for most cases of hand, foot and mouth disease (HFMD) worldwide.

In this study, we examine the molecular mechanism by which RV P protein determines viral pathogenicity by comparing the IFN antagonist activities of the Nishigahara and Ni-CE P proteins. The results, obtained from both RV-infected cells and cells transfected to express P protein only, show that Ni-CE P protein is significantly impaired for its capacity to block IFN-activated STAT1 nuclear translocation and, consequently, inhibits IFN signaling less efficiently than Nishigahara P protein. Further, it was demonstrated that a defect in the nuclear export of Ni-CE P protein correlates https://www.selleckchem.com/products/pf-562271.html with a defect in its ability to cause the mislocalization of STAT1. These data provide the first evidence that

the capacity of the RV P protein to inhibit STAT1 nuclear translocation and IFN signaling correlates with the viral pathogenicity.”
“The nucleus accumbens (NAcc) mediates feeding reward; its learn more activity reflects tastants’ hedonic value. NAcc dopamine guides immediate responses to reward, however, its involvement in establishing long-term responses after a period of exposure to palatable foods has not been defined. Furthermore, reward-driven overeating propels weight increase, but the scale of weight gain depends on animals’ obesity-prone (OP) or -resistant (OR) phenotype. It is unclear whether the NAcc dopamine response to palatable food depends on obesity susceptibility. We investigated the effect

of unrestricted extended access to high-fat high-sugar (HFHS) diet on expression of genes encoding dopamine receptors in the NAcc of OP and OR rats. We examined persistence of HFHS diet-induced changes in D(1) and D(2) gene expression in OP and OR rats subjected to HFHS withdrawal (bland chow for 18 days). Effects of restricted access to HFHS by pair-feeding were also studied. Using reverse transcriptase PCR (RT-PCR), we found that NAcc YM155 molecular weight D(1) mRNA was downregulated after long-term HFHS access in OP vs. OR animals. The effect was also observed after 18 days of HFHS withdrawal. Furthermore, restricted HFHS led to downregulation of D(1) as well as of D(2) mRNA levels compared to chow-fed controls. A

difference in the expression of mu opioid receptor in the NAcc was also detected between the OP and OR rats during access to palatable food but not after withdrawal. We conclude that exposure to HFHS diets has lasting consequences for the NAcc dopamine system, perhaps modifying the motivation to search for food reward. The fact that the NAcc D(1) expression changes in OP animals after long-term exposure to palatable food and that this effect extends well into the reward discontinuation phase, implicates the D(1) receptor in the propensity to overeat and, in effect, gain weight in obesity prone individuals. (C) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Group A rotaviruses (RV), members of the Reoviridae family, are a major cause of infantile acute gastroenteritis.

(C) 2009 Elsevier Inc. All rights reserved.”
“This study was aimed to assess the content of total Fe, Ferritin (Ft) and labile Fe pool (LIP) in developing rat brain exposed in utero to 1 Gy of gamma-irradiation. A significant increase (2.3-fold) in the total Fe content of the fetal rat brain irradiated in utero was observed from 1 to 4 h post-irradiation, as compared to the content in non-irradiated brain. Ft was analyzed by immunoblotting. The Ft protein was composed

by 20 kDa subunits. According to the analysis of the band density in the Western blot, the Ft content decreased by 77 +/- 15%2 h after gamma-irradiation, as compared to the values in non-irradiated samples. The effect of gamma-irradiation

on the LIP was studied APR-246 cell line by both electron paramagnetic resonance (EPR) and by a fluorescence technique employing calcein (CA). A reduction on the LIP was detected at 2 h post-irradiation, independently of the methodology employed AZD3965 mw for the assay. Since NO content increased in the same time frame of LIP decreasing, a protective role for NO is suggested in fetal rat brain exposed to gamma-irradiation. The data presented in this work are the first experimental evidence suggesting that, as part of the network of the cellular response to limit irradiation-dependent injury, a complex interaction between Fe and NO could be triggered. (C) 2009 Elsevier Inc. All rights reserved.”
“Diadenosine tetraphosphate (AP(4)A), two adenosine moieties bridged by four phosphates, is an endogenous purinergic ligand found in brain. Previous studies have shown that ANA reduced neurodegeneration caused by the dopaminergic

neurotoxin 6-hydroxydopamine in rat striatum and substantia nigra. The purpose of this study was to determine whether AP4A is protective against methamphetamine (MA)-mediated toxicity. Primary neuronal cultures were prepared from rat embryonic (E14-E15) ventral mesencephalic tissue. Cultures treated with 2 mM MA exhibited decreased tyrosine hydroxylase (TH) immunoreactivity and increased cleaved caspase-3 immunoreactivity and TUNEL labeling. All these changes were lessened by pretreatment with AP(4)A. The protective effect of AP(4)A was also found in vivo. Adult MycoClean Mycoplasma Removal Kit Sprague-Dawley rats were injected with AP(4)A (25 mu g/20 mu l) or vehicle intracerebroventricularly followed by 4 doses of MA (5 or 10 mg/kg), given subcutaneously every 2 h. Administration of MA reduced locomotor activity 1 day after injection, which was significantly antagonized by the pretreatment with AP(4)A. Using immunohistochemical analysis, TH fiber density at the substantia nigra pars reticulata was found reduced while cleaved caspase-3 immunoreactivity in striatum was increased after MA treatment; these responses were also significantly antagonized by AP(4)A.