Identification of the putative ancestral allele of bovine single-nucleotide polymorphisms.

Identifying the action of natural selection from patterns of standing genetic variation has long been of interest to the population genetic community. Thanks to the availability of large single-nucleotide polymorphism (SNP) data sets for many species and of high-throughput SNP genotyping methods, whole-genomic surveys to detect selective sweeps are now possible. Knowing the ancestral allele increases the power to detect selection. We present here a comparative genomic approach to determine the putative ancestral allele of bovine SNPs deposited in public databases. We analysed 19,551,488 SNPs and identified the putative ancestral allele for 14,339,107 SNPs. Our predicted ancestral alleles were in agreement with ancestral alleles detected by genotyping outgroup species for 97% SNPs from the BovineSNP50 BeadChip. This comparison indicates that our comparative genomic-based approach to identify putative ancestral alleles is reliable.

Point-of-care lung ultrasound in children with bronchiolitis in a pediatric emergency department.

OBJECTIVES: This study assessed the association between findings of lung ultrasound (LUS) performed in the pediatric emergency department (PED) on infants with bronchiolitis and need for respiratory support. METHODS: An observational study was carried out in the PED during the epidemic seasons in two consecutive years. Infants diagnosed with bronchiolitis who fulfilled the inclusion criteria were evaluated. A group of six pediatricians performed LUS and classified lung findings into four groups: normal pattern (A), moderate interstitial pattern (B1), severe interstitial pattern (B2), and isolated consolidation (C). The relationship between LUS findings and need for respiratory support was explored. An expert sonographer, blinded to the results, reviewed the ultrasound studies to determine the interobserver reliability. RESULTS: A total of 200 infants were included (mean age 5.7 months±4.4 SD); 65 (32.5%) obtained moderate clinical scores, while 23 (11.5%) needed respiratory support at admission and 34 (17.0%) at 48h. The ultrasound findings in the PED were the following: A=89 (44.5%), B1=55 (27.5%), B2=34 (17%), and C=22 (11%). Age less than 6 weeks and moderate bronchiolitis were correlated with abnormal LUS (P<0.005). The severity of interstitial ultrasound pattern has some correlation with an increased need for respiratory support. The interobserver concordance was high (0.95, confidence interval: 0.92-0.98). CONCLUSION: LUS is a feasible tool that may help to confirm the clinical impression and assess the need for respiratory support in children with bronchiolitis, but further multicenter studies are needed.

Longitudinal study of bone mineral density in children after a diagnosis of Crohn's disease.

AIM: The purpose of this study was to measure the bone mineral density (BMD) of children with Crohn's disease (CD) and to prospectively assess its evolution. PATIENTS AND METHODS: A total of 27 children (20 boys, seven girls), aged 12.1±2.5 years, were recruited at the time of CD diagnosis. Dual-energy X-ray absorptiometry (DEXA) was used to measure BMD, expressed as Z scores for chronological age (BMD/CA) and bone age (BMD/BA). One year later, BMD was measured again to identify any correlations with disease activity [group A (active disease) vs group R (remission)]. RESULTS: BMD/CA and BMD/BA were negatively correlated with delay in diagnosis (P<0.0001 and P<0.05, respectively). BMD/CA was less than -2 standard deviation (SD) in nine patients and BMD/BA was less -2 SD in four patients. At the follow-up, the increase in BMD was smaller in group A (n=14), whether expressed as absolute values (-0.002 vs 0.040 g/cm(2) per year; P<0.024) or as percentages (-0.2 vs 6.6%; P<0.041); changes in BMD/CA (-0.5 vs -0.1 SD/year) and BMD/BA (-0.3 vs 0 SD/year) did not differ. CONCLUSION: Diagnostic delay greatly affects BMD in children with CD even prior to corticosteroid therapy. The risk of low BMD increases with persistent CD activity, although the risk is reduced in association with bone maturation delay.

Psychological distress experiences of Nigerians during Covid-19 pandemic; the gender difference.

This study examine the psychological distress experience of Nigerians during the COVID-19 pandemic, across gender. From March 20, 2020, to April 12, 2020, this descriptive survey used a snowballing sampling technique to select 502-Nigerians with an online semi-structured questionnaire detailing the impact of Event Scale-Revised, Generalized Anxiety Disorder - 7 item scale, Patient Health Questionnaire and Insomnia Severity Index. Gender had an insignificant difference in the level of insomnia (χ2 â€‹= â€‹04.93; df â€‹= â€‹3; p â€‹> â€‹0.05), however, 20.8% of males had sub-threshold of insomnia, 8.2% experienced moderate insomnia and 5.9% had severe insomnia; 32% females reported sub-threshold of insomnia, 12.4% had moderate insomnia while 3.6% had severe insomnia. Also, gender had an insignificant difference in the measures of depression (χ2 â€‹= â€‹01.94; df â€‹= â€‹4; p â€‹> â€‹0.05); 55.4% males reported minimal depression, 22.3% had mild depression, 11.9% had moderate depression; 6.7%-3.7% males had moderate to severe depression while, 49.3% of the females had minimal depression, 26.7% reported mild depression, 14.29% had moderate depression, 4.4%-5.3% had moderate to severe depressive symptoms. Posttraumatic Stress Symptoms (PTSS) has no gender difference among respondents (χ2 â€‹= â€‹02.51; df â€‹= â€‹3; p â€‹> â€‹0.05); 23% of males reported partial PTSS, 17.5% presented clinical PTSS, and 21.6% males had severe PTSS; while 29.3% of females had severe PTSS, 24% reported partial PTSS and 18.7% had clinical PTSS. Respondents reported insignificant gender differences on anxiety (χ2 â€‹= â€‹0.08; df â€‹= â€‹1; p â€‹> â€‹0.05), while 51% reported moderate anxiety and 49% exhibited severe anxiety during the COVID-19 pandemic in Nigeria. Findings revealed that Nigerians experienced psychological distress during COVID-19 pandemic. The government and stakeholders should initiate tele-mental health services to serve as alternative to traditional treatment to manage present and future pandemic psychological implications among Nigerians.

Interactions Between Socioeconomic Status and Mental Health Outcomes in the Nigerian Context Amid COVID-19 Pandemic: A Comparative Study.

This study examines the mental health outcomes among the healthcare personnel and the general population and the role of socioeconomic status. Eight hundred and eighty-four (884) residents in Nigeria comprising 382 healthcare personnel and 502 general residents aged between 18 to 78 years (M = 28.75, SD = 8.17) responded to an online survey with measures of Impact of Event Scale-Revised (IES-R), Generalized Anxiety Disorder (GAD-7), Patient Health Questionnaire (PHQ-9), and Insomnia Severity Index. Collected data were subjected to statistical analysis using the SPSS v.25. Results revealed significant difference in the prevalence of depressive symptoms (χ2 = 14.26; df = 4; p < 0.01), insomnia symptoms (χ2 = 40.21; df = 3; p < 0.01), posttraumatic stress symptoms (χ2 = 08.34; df = 3; p < 0.05), and clinical anxiety symptoms (χ2 = 06.71; df = 1; p < 0.05) among healthcare personnel and the general population, with a higher prevalence reported by the healthcare personnel. Further, socioeconomic status significantly influences prevalence of depressive symptoms (χ2 = 04.5; df = 4; p < 0.05). The study concluded that the prevalence of poor mental health outcomes during the COVID-19 crisis among Nigerians is worrisome. Also, the socioeconomic status of the citizens has serious implications on depressive symptoms. The study recommends that the government and stakeholders should pay attention to policy that will favor tele-mental health services and adequate palliative measures to cushion the psycho-economic impacts of COVID-19 on residents. Also, healthcare workers should be considered for better remuneration and other welfare benefits to sustain their well-being during the present and future pandemic.

Axoplasmic transport in the crayfish nerve cord. The role of fibrillar constituents of neurons.

(a) Axoplasmic transport of tritium-labeled proteins in crayfish nerve cord was confirmed at a slow rate of 1 mm/day. A second proteinaceous component which moves at a rate of 10 mm/day was also detected. Radioautography and biochemical analysis indicate that proteins migrating at these velocities have a perikaryal origin and move caudad within axons as sharply defined peaks. (b) Evidence is presented for the blockage of the slow and the fast movement of proteins by intraganglionic injection of the anti-mitotic agent vinblastine sulfate (0.1 mM). (c) Electron microscope observations of vinblastine-treated ganglia revealed a reduction in the number of axonal microtubules and the formation of intracellular aggregates presumably composed of microtubular protein. (d) These findings would be compatible with the involvement of microtubules in both slow and fast axoplasmic transport. However, the block induced by vinblastine was detected in regions of the cord (up to 10 mm away from the injection site) where the number and morphology of microtubules appeared unaltered. In addition, axons showing effects of vinblastine occasionally contained mitochondria with remarkably dense and thickened membranes. (e) In association with the surfaces of axonal microtubules are lateral filamentous elements (40-80 A in diameter) which also showed vinblastine-induced alterations. Our observations indicate that such filiform structures, associated with microtubules, may be a necessary component in the transport mechanism(s).

Incidence of Breast Cancer in Eritrea: A Retrospective Study from 2011 to 2017.

In Africa, breast cancer closely compares with cervical cancer as the most common malignancy affecting women and the incidence rates appear to be rising. Eritrea is experiencing a growing breast cancer problem, but little is presently known on tumor patterns, breast cancer epidemiology, and risk factors. The main objective of this study is to provide baseline data on breast cancer incidence in both sexes in Eritrea. This study was carried out retrospectively and quantitatively by collecting, abstracting, analyzing, coding, and interpreting data recorded in National Health Laboratory (NHL) using CanReg5 ver. 5.00.35. Extracting and classification of the tumor data was done using topography, morphology together with the ICD-10. To generate the incidence rate for the seven years the Eritrean population dataset was used from the population pyramid net for 2014. After we entered all the data from Pathology department in NHL, data was analyzed using the predetermined and developed built-in analysis tools of CanReg5 software and Microsoft Excel 2010. A total number of 9,403 pathology cases were recorded from 2011 to 2017. Out of these 1,497 cases were confirmed as cytology and histology of breast cases. From 1,497 confirmed breast cases in both sexes, the incidence of benign cases was higher than incidence of malignant cases with the case number of 1, 149, and 348, respectively. Out of the 1,497 cases, 1,447 (96.66%) were females; this included a total incidence cases of female benign and malignant breast cases 1,111 (76.78%), and 336 (23.22%), respectively. In both female and male age group the highest positive cases were found in the age greater than 85. The incidence age standard rate per 100,000 in females and male was 3.3 and 0.2, respectively. In sum, the age standardized incidence of breast cancer was relatively low. However, it is our opinion that the low prevalence may be due to low awareness and a highly centralized screening and diagnostic services. This limits access. Altogether, it is our opinion that breast cancer presents a burden to Eritrean ministry of health.

Gyrification changes are related to cognitive strengths in autism.

Background: Behavioral, cognitive and functional particularities in autism differ according to autism subgroups and might be associated with domain-specific cognitive strengths. It is unknown whether structural changes support this specialization. We investigated the link between cortical folding, its maturation and cognitive strengths in autism subgroups presenting verbal or visuo-spatial peaks of abilities. Methods: We measured gyrification, a structural index related to function, in 55 autistic participants with (AS-SOD, N = 27) or without (AS-NoSOD, N = 28) a speech onset delay (SOD) with similar symptom severity but respectively perceptual and verbal cognitive strengths, and 37 typical adolescents and young adults matched for intelligence and age. We calculated the local Gyrification Index (lGI) throughout an occipito-temporal region of interest and independently modeled age and peak of ability effects for each group. Results: Unique gyrification features in both autistic groups were detected in localized clusters. When comparing the three groups, gyrification was found lower in AS-SOD in a fusiform visual area, whereas it was higher in AS-NoSOD in a temporal language-related region. These particular areas presented age-related gyrification differences reflecting contrasting local maturation pathways in AS. As expected, peaks of ability were found in a verbal subtest for the AS-NoSOD group and in the Block Design IQ subtest for the AS-SOD group. Conclusions: Irrespective of their direction, regional gyrification differences in visual and language processing areas respectively reflect AS-SOD perceptual and AS-NoSOD language-oriented peaks. Unique regional maturation trajectories in the autistic brain may underline specific cognitive strengths, which are key variables for understanding heterogeneity in autism.

FLAGdb/FST: a database of mapped flanking insertion sites (FSTs) of Arabidopsis thaliana T-DNA transformants.

A large collection of T-DNA insertion transformants of Arabidopsis thaliana has been generated at the Institute of Agronomic Research, Versailles, France. The molecular characterisation of the insertion sites is currently performed by sequencing genomic regions flanking the inserted T-DNA (FST). The almost complete sequence of the nuclear genome of A.thaliana provides the framework for organising FSTs in a genome oriented database, FLAGdb/FST (http://genoplante-info.infobiogen.fr). The main scope of FLAGdb/FST is to help biologists to find the FSTs that interrupt the genes in which they are interested. FSTs are anchored to the genome sequences of A.thaliana and positions of both predicted genes and FSTs are shown graphically on sequences. Requests to locate the genomic position of a query sequence are made using BLAST programs. The response delivered by FLAGdb/FST is a graphical representation of the putative FSTs and of predicted genes in a 20 kb region.

Action of the vinca alkaloids vincristine, vinblastine, and desacetyl vinblastine amide on microtubules in vitro.

The Vinca alkaloids differ in their chemotherapeutic effectiveness and their toxicities. To determine whether differences are due to a differential effect on the assembly of tubulin into microtubules, we examined the effects of vincristine, vinblastine, and a newer alkaloid, desacetyl vinblastine amide, on the assembly of bovine brain tubulin in vitro. The three compounds block bovine tubulin polymerization in vitro and almost equally effectively at a 1 muM concentration (tubulin, 6.5 muM). At 10 muM, the three alkaloids also interact with preformed microtubules in vitro, causing spiral-like distortions of the microtubules. No effect of the alkaloids on polymerization of another fibrous protein, actin, was observed. Thus the differential actions of vinblastine, vincristine, and desacetyl vinblastine amide in vivo seems to be based on some biological process other than the reaction with tubulin or the microtubules per se.

Action of the vinca alkaloids vincristine, vinblastine, and desacetyl vinblastine amide on axonal fibrillar organelles in vitro.

Axonal ultrastructural changes induced by three Vinca alkaloids, vincristine, vinblastine, and desacetyl vinblastine amide, were studied in vitro at concentrations of 0.01, 0.05, and 0.1 mM in the cat vagus nerve. Disruption of microtubules, appearance of paracrystalline structures, and increase in neurofilaments were induced by all three agents at 0.1 mM. A new type of paracrystal with an electron-dense central core in each subunit was also observed with each drug. Whereas all three compounds affected unmyelinated fibers (vinblastine more so than the other two), only vinblastine significantly damaged the myelinated fibers. The greater effectiveness of vinblastine in causing these in vitro ultrastructural changes contrasts strikingly with the clinical in vivo situation in which vincristine is the most neurotoxic. This suggests that clinical neurotoxicity is associated with additional factors aside from the direct interaction of the Vinca alkaloids with microtubules or tubulin.

Maytansine action on fast axoplasmic transport and the ultrastructure of vagal axons.

Maytansine, an ansa macrolide now in clinical trials as an antineoplastic drug, is a potent inhibitor of microtubule polymerization. Since microtubules are involved in axoplasmic transport, the effect of maytansine on transport was examined. Fast axoplasmic transport of proteins and the axonal ultrastructure was studied in the vagus nerve of cats exposed in vitro to maytansine. Tritiated leucine was microinjected into the nodose ganglion; after 2 hr for incorporation into proteins, nerves were dissected out for transport and ultrastructural studies and incubated for 2.5 hr in Krebs-Ringer solution with 100, 20, 10, 5, or 1 micron maytansine. A reduction in the number of microtubules and a partial blockage of fast axoplasmic transport was observed at 20 and 100 micron maytansine; at 10 micron no detectable changes were observed. These findings show that maytansine in vitro induces alterations of the neurofibrillar elements concomitant with a partial blockage of fast axoplasmic transport.

Hazard functions and expected spike density functions for neuron spike activity in the cochlear nucleus of the cat.

The goal of these experiments was to evaluate the effect of stimulus evoked input and post spike refractoriness on the shapes of post stimulus time histograms (PSTHs). The time courses of spontaneous and/or evoked activity were studied in 153 neurons located predominantly in the dorsal cochlear nucleus in cats anesthetized with Nembutal. Tone bursts were presented to the ipsilateral ear in a free sound field. About half the cells were characterized by the pauser/build-up type of PSTH. Marked refractoriness was evidenced by relatively long recovery times of the hazard functions of spontaneous and tone-evoked spike activity. On presentation of tonal bursts, the time dependence of the probability of the first spike in the absence of a preceding spike (expected spike density function) was greater than the PSTH (actual spike density function). The initial PSTH peak with pause was shaped primarily by stimulus evoked input, whereas refractoriness tended to diminish the build-up portion of the PSTH. In chopper cells, PSTH peaks were usually not reflected in expected spike density functions showing that post spike refractoriness plays a major role in shaping the PSTH. In primary-like cells, refractoriness was small and had little effect on the shape of the PSTH. Some presumptively inhibitory cells showed a tendency to burst discharges with non-monotonic hazard functions. A very small number of cells showed a tendency to internal tuning to a defined signal periodicity.

Decreased type VI adenylyl cyclase mRNA concentration and Mg(2+)-dependent adenylyl cyclase activities and unchanged type V adenylyl cyclase mRNA concentration and Mn(2+)-dependent adenylyl cyclase activities in the left ventricle of rats with myocardial infarction and longstanding heart failure.

OBJECTIVE: To address the effect of longstanding left ventricular (LV) hypertrophy and failure on LV adenylyl cyclase (AC) gene expression, mRNA concentrations of the main cardiac AC isoforms were measured in the non-infarcted area of LV from rats with myocardial infarction (MI), without (H) or with (F) LV failure, and in control (C) rats. Basal, GTP- and forskolin-stimulated Mg(2+)- and Mn(2+)-dependent AC activities were also measured in F and C rats. METHODS: Two- and six months after MI, steady-state AC mRNA concentrations were assessed by Northern blot analysis and RNase protection assay with isoform-specific cDNA and cRNA probes, respectively. AC activities were assessed on LV microsomal fractions using standard procedures. RESULTS: Types V and VI, and types IV and VII were the major and minor AC mRNA isoforms in both the LVs of F and C rats. Two months after MI, no difference in LV type V or VI mRNA to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA ratios was observed in rats with H or F compared to C. Six months after MI, no difference in LV type V mRNA concentration was observed between the three rat groups, whether this level was normalized to GAPDH, poly-(A+) or 18S RNAs. In contrast, a 35% decrease in the type VI mRNA to poly-(A+) RNA ratio and a 29% decrease in the type VI mRNA to 18S RNA ratio was observed only in rats with F compared to C (p < 0.05 vs. C for the two comparisons). Two- and six months after MI, basal and forskolin-stimulated Mg(2+)-dependent AC activities were decreased by 30-35% in F rats compared to C (p < 0.05), whereas Mn(2+)-dependent activities were unchanged. CONCLUSION: Longstanding LV hypertrophy and failure resulting from MI in rats is not associated with altered expression of the most abundant, type V, AC mRNA isoform, whereas that of type VI is decreased. The lack of change in Mn(2+)-dependent AC activities in the LV of F rats suggests that this decrease has no functional consequence on overall AC activity and that decreased Mg(2+)-dependent activities are related to alterations occurring upstream.

Speech acquisition predicts regions of enhanced cortical response to auditory stimulation in autism spectrum individuals.

A continuum of phenotypes makes up the autism spectrum (AS). In particular, individuals show large differences in language acquisition, ranging from precocious speech to severe speech onset delay. However, the neurological origin of this heterogeneity remains unknown. Here, we sought to determine whether AS individuals differing in speech acquisition show different cortical responses to auditory stimulation and morphometric brain differences. Whole-brain activity following exposure to non-social sounds was investigated. Individuals in the AS were classified according to the presence or absence of Speech Onset Delay (AS-SOD and AS-NoSOD, respectively) and were compared with IQ-matched typically developing individuals (TYP). AS-NoSOD participants displayed greater task-related activity than TYP in the inferior frontal gyrus and peri-auditory middle and superior temporal gyri, which are associated with language processing. Conversely, the AS-SOD group only showed enhanced activity in the vicinity of the auditory cortex. We detected no differences in brain structure between groups. This is the first study to demonstrate the existence of differences in functional brain activity between AS individuals divided according to their pattern of speech development. These findings support the Trigger-threshold-target model and indicate that the occurrence of speech onset delay in AS individuals depends on the location of cortical functional reallocation, which favors perception in AS-SOD and language in AS-NoSOD.

The histopathology of freezing injury to the rat spinal cord. A light microscope study. I. Early degenerative changes.

In an effort to develop a method of tissue injury which would provide a model for the study of axonal regrowth in adult mammalian central nervous system (CNS), we have analyzed the effects of freezing in the dorsal columns of more than 200 rat spinal cords. The effects of temperature and time of exposure upon the size, shape, distribution and histologic characteristics of the lesion have been assessed during the first seven days following the injury. The upper threshold for injury occurs at -3 degrees C for 15 minutes. Between -3 degrees C and -12 degrees C the tissue changes vary in extent and characteristics. Selective damage to axons and myelin occurs with sparing of the supportive cells followed by proliferation of a cellular matrix. At seven days, the lesions produced by -8 degrees C for 15 to 60 minutes have neither axons nor myelin sheaths and consist of a dense cellular matrix of macrophages and presumed glial cells. With these tissue characteristics, and the preservation of tissue continuity without obstructive barriers, this model would appear to be potentially suitable for the study of axonal regrowth potential in mammalian CNS.

Molecular cloning and developmental expression of human cardiac troponin T.

We have isolated a full-size cDNA coding for cardiac troponin T (cTnT) from a human adult heart library, using a slow skeletal TnT probe. This cDNA detected a 1.2 kb mRNA in fetal and post-natal human heart, the amount of which increased during ontogenic development. Interestingly, a similar transcript was coexpressed in fetal skeletal muscle, together with the 0.9 kb slow skeletal muscle mRNA, and its expression was down-regulated during further development.

Kainic acid causes redox changes in cerebral cortex extracellular fluid: NMDA receptor activity increases ascorbic acid whereas seizure activity increases uric acid.

Kainic acid (KA) causes seizures and extensive brain damage in rats. To study the effects of KA on the redox state in cerebral cortex extracellular fluid (ECF), ascorbic and uric acid concentrations were measured in intracerebral microdialysis samples before and after systemic KA administration (ip). During seizures, concentrations of ascorbic and uric acid increased 500 and 100%, respectively. When midazolam was given with KA to prevent seizures, ascorbic acid still increased 400%, but uric acid increased only transiently. When the NMDA receptor antagonist aminophosphonovaleric acid (APV) was included in the microdialysis perfusion media, ascorbic acid levels decreased during baseline perfusion in a concentration-dependent manner. APV then suppressed the KA-induced increase in ascorbic acid levels, without blocking seizure activity. In summary, increased uric acid levels in brain ECF activity after KA administration are related to the induced seizure, but ascorbic acid levels are associated with NMDA receptor activity.

Effects of microdialysis on brain metabolism in normal and seizure states.

The effect of intracranial microdialysis on brain glucose metabolism in control and kainic acid-treated rats was assessed by semi-quantitative [14C]2-deoxyglucose autoradiography. A dialysis fiber loop was implanted into the piriform cortex or a horizontal Vita fiber into the hippocampus, and 24 h later, fibers were perfused with Krebs-Ringer bicarbonate solution before and after injection of kainic acid (16 mg/kg, i.p.) [14C]2-Deoxyglucose was injected i.p. 3 h after the injection of kainic acid. Rats injected with kainic acid were initially lethargic and then proceeded through behavioral phases of staring, "wet-dog shakes", Straub tail, rearing, forepaw clonus, and, in some cases, tonic-clonic convulsions. Three hours after kainic acid, the fiber presence in the piriform cortex enhanced kainic acid-induced metabolic activity in areas adjacent to the fiber assembly, whereas the fiber in hippocampus attenuated kainic acid-induced metabolic activity in areas adjacent to the fiber assembly. The results indicate that intracranial microdialysis alters the already abnormal brain metabolism in a kainic acid-induced seizure state, but has no significant effect in the non-seizure control state.

Topographical distribution of down-regulated muscarinic receptors in rat brains after repeated exposure to diisopropyl phosphorofluoridate.

Quantitative receptor autoradiography demonstrated that muscarinic receptors were down-regulated in Wistar rats after repeated exposure to diisopropyl phosphorofluoridate. The density of receptors was decreased to 60-85% of the controls. Reductions in muscarinic receptor binding were observed in cortex, caudate-putamen, lateral septum, hippocampal formation, superior colliculus, and pons. The density of muscarinic receptors was unchanged in thalamic and hypothalamic nuclei, periaqueductal grey, cerebellum, inferior colliculus and reticular formation of the brain stem. The down-regulation of muscarinic receptors in forebrain structures, such as cortex, caudate-putamen and hippocampus, may be important in the adaptation to the behavioral effects of organophosphate poisons.