Midbrain Level Research Articles

Motivated Behaviors and Levels of 3α,5α-THP in the Midbrain are Attenuated by Knocking Down Expression of Pregnane Xenobiotic Receptor in the Midbrain Ventral Tegmental Area of Proestrous Rats

Progesterone (P4 ) and its product, 5α-pregnan-3α-ol-20-one (3α,5α-THP), act in the midbrain ventral tegmental area (VTA) to alter motivated behaviors, such as mating, and motor and anxiety behavior. Of interest is whether 3α,5α-THP formation requires the pregnane xenobiotic receptor (PXR), which is expressed in the midbrain of rats. The role of PXR in the midbrain for 3α,5α-THP formation, which precedes modulation of motivated behaviors, was investigated. Rats had estrous cycle phase determined and were assessed when they were in diestrus or proestrus. Diestrous and proestrous rats were infused with control or antisense oligodeoxyribonucleotides (AS-ODNs) targeted against PXR to the VTA. In pilot studies, PXR gene and protein expression in the midbrain were determined with quantitative reverse transcriptase polymerase chain reaction and Western blotting, respectively. Diestrous and proestrous rats infused with control or AS-ODNs to the VTA were tested for anxiety (open field and plus maze), social (social interaction), and sexual (paced mating) behavior. Expression of PXR in the midbrain was verified with Western blotting. Plasma estradiol, P4 , dihydroprogesterone (DHP), and 3α,5α-THP levels, and brain P4 , DHP, and 3α,5α-THP levels were measured. We predicted that proestrous rats infused with PXR AS-ODNs would have decreased anti-anxiety, social, and sexual behavior, lower midbrain expression of PXR, and lower midbrain levels of 3α,5α-THP compared with controls. Results supported the hypothesis that formation of 3α,5α-THP requires PXR and may be important for motivated behaviors. PXR AS-ODN, compared with control, infusions to the VTA reduced PXR expression and 3α,5α-THP levels in the midbrain and attenuated sexual receptivity of proestrous rats. Knockdown of PXR in the midbrain reduces 3α,5α-THP levels and sexual receptivity of proestrous rats. Thus, PXR in the midbrain may be required for the observed increase in 3α-5α-THP during proestrus, which has subsequent effects on motivated, reproductive behaviors.

SP0170 Descending Modulation of Pain

There is clear evidence from both preclinical and clinical studies that both peripheral and central hyperexcitability play important roles in determining the level of pain perceived. Rightly, much emphasis has...

Proximal weakness due to injury of the corticoreticular pathway in a patient with traumatic brain injury

The corticoreticular pathway (CRP) innervates the proximal muscles of extremities and axial muscles; therefore, it is involved in postural control and gait. We report on a patient who exhibited proximal weakness due to a CRP injury, which was evaluated using diffusion tensor tractography (DTT). A 62-year-old male patient who had been injured in a traffic accident underwent conservative management for a contusional hemorrhage in the right frontotemporal lobes, and a subdural and epidural hematoma in the right temporoparietal lobes. The patient exhibited right proximal weakness (shoulder: 3+, hip: 3+) at two weeks after onset. Findings on brain MRI revealed encephalomalactic lesions in both frontal lobes. Findings on DTT of the left CRP showed discontinuation at the midbrain level; in contrast, the integrities of the corticospinal tract in both hemispheres were maintained from the cerebral cortex to the medulla along the known pathway of the corticospinal tract. The proximal weakness of the right shoulder and hip observed in this patient appeared to be attributed to injury of the left CRP.

Recovery of an injured corticospinal tract and an injured corticoreticular pathway in a patient with intracerebral hemorrhage

The main function of the corticospinal tract (CST) is control of the distal musculature used for fine movements, in contrast, the corticoreticular pathway (CRP) innervates the proximal and axial musculature. We report on a patient with an intracerebral hemorrhage (ICH) who showed recovery of an injured CST and an injured CRP by diffusion tensor tractography (DTT). The patient, a 38-year-old man, presented with severe paralysis of the right upper and lower extremities due to a spontaneous ICH in the left corona radiata and basal ganglia. When he started rehabilitation at 3 weeks after onset, he showed more severe weakness in the proximal joints (shoulder and hip joints) than distal joints (hand and ankle joints). This proximal weakness improved rapidly in parallel with distal weakness over 3 weeks of rehabilitation. DTT performed at 3 and 6 weeks post-ICH revealed that a thin left CST observed at 3 weeks thickened at 6 weeks, and that a discontinuation of the left CRP at the midbrain level at 3 weeks was restored at 6 weeks. In addition, the track volumes of the left CST and CRP increased from 221 and 244 at 3 weeks to 725 and 625 at 6 weeks. In conclusion, we demonstrated the recovery of an injured CST and an injured CRP in a patient with ICH.

Live image profiling of neural crest lineages in zebrafish transgenic lines.

Zebrafish transgenic lines are important experimental tools for lineage tracing and imaging studies. It is crucial to precisely characterize the cell lineages labeled in transgenic lines to understand their limitations and thus properly interpret the data obtained from their use; only then can we confidently select a line appropriate for our particular research objectives. Here we profiled the cell lineages labeled in the closely related neural crest transgenic lines Tg(foxd3:GFP), Tg(sox10:eGFP) and Tg(sox10:mRFP). These fish were crossed to generate embryos, in which foxd3 and sox10 transgenic neural crest labeling could be directly compared at the cellular level using live confocal imaging. We have identified key differences in the cell lineages labeled in each line during early neural crest development and demonstrated that the most anterior cranial neural crest cells initially migrating out of neural tube at the level of forebrain and anterior midbrain express sox10:eGFP and sox10:mRFP, but not foxd3:GFP. This differential profile was robustly maintained in the differentiating progeny of the neural crest lineages until 3.5dpf. Our data will enable researchers to make an informed choice in selecting transgenic lines for future neural crest research.

Catecholamine Contents of Different Region of Adult Rat Brain Are Altered Following Short and Long-term Exposures to Pb(+2.).

Catecholamine is a group of neurotransmitters that is believed to be responsible for the normal function of animal brain. Physiological and behavioral changes of human body have been reported due to the damage of the brain function following lead exposure. Due to the assumption of lead disposal in brain tissue with two year for its half-life, which results in alteration of brain function, we investigated the ability of lead to change the brain catecholamines during short and long-term studies. Rats were exposed daily with varying amounts of lead and catecholamine contents of cerebellum, mid-brain and brain cortex were determined. Acute peritoneal administration of single dose of lead as lead acetate (260 μmol/Kg) after 2 h reduced (p < 0.05) the catecholamine levels of cerebellum, mid-brain and cortex part by 34.9%, 35.44% and 23.8%, respectively. The extension of experiment time to 5 h, significant (p < 0.05) reductions in catecholamine levels of mentioned regions of brain by 32.35%, 12.35% and 19.3% were seen respectively. Daily intraperitoneal administration of 10 μmol/Kg lead for 30 and 60 days reduced catecholamines levels of cerebellum (22.22% and 30.44%), midbrain (12.48% and 26.27%) and brain cortex (11.58% and 26.7%) respectively. It might be concluded that brain dysfunction in lead intoxicated rat occurred through the reduction in the catecholamine levels of different parts of brain. Lead might be therefore considered as a probable factor in causing neurological disease in lead exposed man.

Type-2 diabetes mellitus and auditory brainstem response

Objective:Diabetes mellitus (DM) causes pathophysiological changes at multiple organ system. With evoked potential techniques, the brain stem auditory response represents a simple procedure to detect both acoustic nerve and central nervous system pathway damage. The objective was to find the evidence of central neuropathy in diabetes patients by analyzing brainstem audiometry electric response obtained by auditory evoked potentials, quantify the characteristic of auditory brain response in long standing diabetes and to study the utility of auditory evoked potential in detecting the type, site, and nature of lesions.Design:A total of 25 Type-2 DM [13 (52%) males and 12 (48%) females] with duration of diabetes over 5 years and aged over 30 years. The brainstem evoked response audiometry (BERA) was performed by universal smart box manual version 2.0 at 70, 80, and 90 dB. The wave latency pattern and interpeak latencies were estimated. This was compared with 25 healthy controls (17 [68%] males and 8 [32%] females).Result:In Type-2 DM, BERA study revealed that wave-III representing superior olivary complex at 80 dB had wave latency of (3.99 ± 0.24) ms P < 0.001, at 90 dB (3.92 ± 0.28) ms P < 0.001 compared with control. The latency of wave III was delayed by 0.39, 0.42, and 0.42 ms at 70, 80, and 90 dB, respectively. The absolute latency of wave V representing inferior colliculus at 70 dB (6.05 ± 0.27) ms P < 0.001, at 80 dB (5.98 ± 0.27) P < 0.001, and at 90 dB (6.02 ± 0.30) ms P < 0.002 compared with control. The latency of wave-V was delayed by 0.48, 0.47, and 0.50 ms at 70, 80, and 90 dB, respectively. Interlatencies I-III at 70 dB (2.33 ± 0.22) ms P < 0.001, at 80 dB (2.39 ± 0.26) ms P < 0.001, while at 90 dB (2.47 ± 0.25) ms P < 0.001 when compared with control. Interlatencies I-V at 70 dB (4.45 ± 0.29) ms P < 0.001 at 80 dB (4.39 ± 0.34) ms P < 0.001, and at 90 dB (4.57 ± 0.31) ms P < 0.001 compared with control. Out of 25 Type-2 DM, 13 (52%) had diabetic neuropathy, of which 12 (92%) showed abnormal BERA. In nonneuropathic [12 (48%)] only 6 (50%) showed abnormal BERA.Conclusion:Delay in absolute latencies and interpeak latencies by BERA demonstrates defect at level of brainstem and midbrain in long standing Type-2 diabetes subjects, which is more pronounced in those with neuropathy.

Diffusion tensor tractography in two cases of kernohan-woltman notch phenomenon.

Kernohan-Woltman notch phenomenon (KWP) is an ipsilateral motor weakness due to compression of the contralateral cerebral peduncle. We report two cases of KWP following traumatic brain injury. In case 1, ipsilateral hemiplegia was noted after right subdural hemorrhage. Although magnetic resonance imaging showed no abnormal signal changes on cerebral peduncle, diffusion tensor tractography (DTT) revealed interruption of corticospinal tract (CST) at lower level of the midbrain level. In case 2, there was abnormal signal change of the right cerebral peduncle contralateral to the primary lesion and we could not reconstruct right CST. Case 1 showed unsatisfactory motor recovery even after 15 months, and follow-up DTT showed no change. In case 2, follow-up DTT was not performed, but her ipsilateral hemiparesis had almost disappeared during the 15 months. DTT would be useful in detecting ipsilateral hemiparesis due to KWP and the clinical course may differ according to the lesion characteristics.

Meningioma with intense I123 FP‐CIT uptake

Iodine-123 FP-CIT SPECT images with sections atthe midbrain (A1) and basal ganglia (A2) levels showa roundish area of intense homogeneous uptake in theright middle cranial fossa. The basal ganglia are dis-placed over the midline, and binding looks mildlyreduced in the right putamen and normal in the bilat-eral caudate nucleus. Brain CT (B1) and MRI (C1–C3) demonstrated a 5-cm extraparenchymal mass with

Immunohistochemical study of the distribution of calcium binding proteins in the brain of a chondrostean (Acipenser baeri)

Chondrosteans represent an ancient lineage in ray-finned bony fishes and hence in jawed vertebrates. This immunohistochemical study in the brain of the Siberian sturgeon reports the neuronal distribution of three cytosolic calcium-binding proteins: calbindin-D28k (CB), calretinin (CR), and parvalbumin (PV). CB and CR are widely expressed in different neuron subsets distributed throughout the sturgeon brain. Studies using double immunofluorescence reveal a wide co-distribution of CB and CR in the brain nuclei but scarce co-localization at cellular level. In the forebrain, CR- and CB-immunoreactive (ir) populations were observed in the olfactory bulbs, in pallial and subpallial telencephalic areas, and in some diencephalic nuclei. CR-ir cells were also observed in the posterior tubercle and CB-ir cells in the preglomerular complex. At midbrain and hindbrain basal levels, CB-ir and CR-ir cell bodies were mainly distributed in periventricular areas. In the cerebellum, CB and CR cells were co-localized in some granular cell subsets in laterodorsal and dorsolateral regions, and in some Purkinje-like cells. CB-ir and CR-ir fibers were mainly observed in the olfactory bulbs, hypothalamus, and habenula, and in fiber tracts that coursed in the optic tectum and through the mesencephalic and rhombencephalic basal areas. With regard to PV, the sturgeon brain showed a rather limited distribution of PV-ir perikarya and fibers. Thus, CR, CB, and PV allowed the identification of subpopulations of neurons not distinguished on the basis of cytoarchitecture alone, which provided a better understanding of the anatomical organization of the sturgeon brain. These results reveal numerous shared features with teleosts, but also important differences.

Ectopic Wnt/Beta–Catenin Signaling Induces Neurogenesis in the Spinal Cord and Hindbrain Floor Plate

The most ventral structure of the developing neural tube, the floor plate (FP), differs in neurogenic capacity along the neuraxis. The FP is largely non-neurogenic at the hindbrain and spinal cord levels, but generates large numbers of dopamine (mDA) neurons at the midbrain levels. Wnt1, and other Wnts are expressed in the ventral midbrain, and Wnt/beta catenin signaling can at least in part account for the difference in neurogenic capacity of the FP between midbrain and hindbrain levels. To further develop the hypothesis that canonical Wnt signaling promotes mDA specification and FP neurogenesis, we have generated a model wherein beta–catenin is conditionally stabilized throughout the FP. Here, we unambiguously show by fate mapping FP cells in this mutant, that the hindbrain and spinal cord FP are rendered highly neurogenic, producing large numbers of neurons. We reveal that a neurogenic hindbrain FP results in the altered settling pattern of neighboring precerebellar neuronal clusters. Moreover, in this mutant, mDA progenitor markers are induced throughout the rostrocaudal axis of the hindbrain FP, although TH+ mDA neurons are produced only in the rostral aspect of rhombomere (r)1. This is, at least in part, due to depressed Lmx1b levels by Wnt/beta catenin signaling; indeed, when Lmx1b levels are restored in this mutant, mDA are observed not only in rostral r1, but also at more caudal axial levels in the hindbrain, but not in the spinal cord. Taken together, these data elucidate both patterning and neurogenic functions of Wnt/beta catenin signaling in the FP, and thereby add to our understanding of the molecular logic of mDA specification and neurogenesis.

Speech processing disorder in neural hearing loss.

Deficits in central auditory processing may occur in a variety of clinical conditions including traumatic brain injury, neurodegenerative disease, auditory neuropathy/dyssynchrony syndrome, neurological disorders associated with aging, and aphasia. Deficits in central auditory processing of a more subtle nature have also been studied extensively in neurodevelopmental disorders in children with learning disabilities, ADD, and developmental language disorders. Illustrative cases are reviewed demonstrating the use of an audiological test battery in patients with auditory neuropathy/dyssynchrony syndrome, bilateral lesions to the inferior colliculi, and bilateral lesions to the temporal lobes. Electrophysiological tests of auditory function were utilized to define the locus of dysfunction at neural levels ranging from the auditory nerve, midbrain, and cortical levels.

Significance of Virchow-Robin Spaces in Patients Newly Diagnosed with Multiple Sclerosis: A Case-Control Study in an Arab Population

Objective: To assess the frequency and extent of dilatation of Virchow-Robin (VR) spaces at three levels of the brain in patients of Arab ethnicity in Kuwait recently diagnosed with multiple sclerosis (MS) and compare the results with age- and gender-matched controls. Methods: The magnetic resonance imaging (MRI) scans performed within 3 months of the clinical diagnosis of 80 patients recently diagnosed with active MS were compared to those of 80 age- and gender-matched controls with headache but without any neurological deficits for the frequency and size of VR spaces. MRI was done with noncontrast axial and coronal T₁W FSE, axial T₂W FSE, axial T₂W FLAIR and sagittal FLAIR sequences followed by postcontrast axial and coronal T₁W sequences. The frequency of VR spaces in MS patients and controls at midbrain, lenticulostriate vessels and supraventricular levels was analyzed using a two-tailed McNemar test. Results: There was no difference in the frequency of VR spaces at the levels of the midbrain, lenticulostriate vessels and supraventricular white matter between MS patients and controls. In the supraventricular region, however, there were 91 dilated VR spaces in 26 (32%) of the MS patients while in the control group, there were 8 dilated VR spaces in 6 (7.5%) patients and the difference was statistically significant (p < 0.0001). Conclusion: The data showed that dilated VR spaces in the supraventricular region could potentially be used as a marker for MS and as a prognostic tool. However, further studies with a larger population are needed to further evaluate and confirm this observation.

Clinical significance of the pallidoreticular pathway in patients with carbon monoxide intoxication

Whereas globus pallidus lesions resulting from carbon monoxide intoxication have been extensively described in the literature, the clinical significance of pallidoreticular lesions has rarely been mentioned. This study incorporated information from functional and structural imaging to explore the correlations of pallidoreticular lesions with parkinsonian features and neurobehavioural performance. Twenty-five patients (11 males) with globus pallidus lesions after carbon monoxide intoxication and 25 age- and sex-matched controls were enrolled for detailed neurological examinations, cognitive testing, susceptibility weighted imaging, diffusion tensor imaging and 99mTc-TRODAT-1 single photon emission computed tomography. The post-processing analysis of the neuroimaging included voxel-based morphometry to assess the regional atrophy, tract-based spatial statistics related to white matter involvement, tractography to investigate the rostral and caudal projections from the midbrain level and specific uptake ratios of 99mTc-TRODAT-1 for presynaptic dopaminergic transporter activity. In susceptibility weighted imaging, low-intensity pallidoreticular lesions were detected from the minimal-intensity projections, which were visible in only 7.7% of the T(1)-weighted images and 15.4% of the T(2)-weighted images, whereas inhomogeneous intensities were detected in the globus pallidus. The patients were further divided into two subgroups based on the presence (n = 13) or absence (n = 12) of pallidoreticular lesions. The patients with pallidoreticular lesions showed increased parkinsonian features, poorer performances on the neuropsychiatric tests, lower 99mTc-TRODAT-1 availability in both the caudate and the putamen and greater atrophy of the thalamus, posterior corpus callosum, cerebral peduncle and white matter surrounding the globus pallidus compared to those without pallidoreticular lesions. The tractography results obtained with seed regions of interest in the substantia nigra showed rostral projections to the supplementary motor cortex and anterior cingulate cortex via the globus pallidus; the two pathways were distinct but ran in parallel, caudal to the level of the globus pallidus. In conclusion, the presence of pallidoreticular lesions after carbon monoxide intoxication indicates a poorer cognitive state, which is associated with extensive grey and white matter damage in addition to the damage to the nigra-striatal neuronal networks. The presence of parkinsonian features may be related to pallidal and presynaptic dopaminergic dysfunction. The sensitivity for detecting pallidoreticular lesions can be greatly improved by using susceptibility weighted imaging compared with conventional imaging.

Characteristics of the aberrant pyramidal tract in comparison with the pyramidal tract in the human brain

BackgroundThe aberrant pyramidal tract (APT) refers to the collateral pathway of the pyramidal tract (PT) through the medial lemniscus in the midbrain and pons. Using diffusion tensor tractography (DTT), we investigated the characteristics of the APT in comparison with the PT in the normal human brain.ResultsIn thirty-four (18.3%, right hemisphere: 20, left hemisphere: 14) of the 186 hemispheres, the APTs separated from the PT at the upper midbrain level, descended through the medial lemniscus from the midbrain to the pons, and then rejoined with the PT at the upper medulla. Nine (26.5%) of the 34 APTs were found to originate from the primary somatosensory cortex without a primary motor cortex origin. Values of fractional anisotropy (FA) and tract volume of the APT were lower than those of the PT (P < 0.05); however, no difference in mean diffusivity (MD) value was observed (P >0.05).ConclusionWe found that the APT has different characteristics, including less directionality, fewer neural fibers, and less origin from the primary motor cortex than the PT.

Anatomic Location and Somatotopic Arrangement of the Corticospinal Tract at the Cerebral Peduncle in the Human Brain

Little is known about the detailed anatomic location and somatotopic arrangement at the CP. Using DTT with FSL tools, we conducted an investigation of the anatomic location and somatotopic arrangement of the CST at the CP in the human brain. We recruited 43 healthy volunteers for this study. DTI was obtained by using 1.5T, and CSTs for the hand and leg were obtained by using the FSL tool. The somatotopic location of the CST was evaluated as the highest probabilistic location at the upper and lower midbrain. The posterior boundary was determined as the line between the interpeduncular fossa and the lateral sulcus; we then drew a rectangle on the basis of the boundary of the CP. In the mediolateral direction, the highest probabilistic locations for the hand and leg were an average of 60.46% and 69.98% from the medial boundary at the upper midbrain level and 53.44% and 62.76% at the lower midbrain level, respectively. As for the anteroposterior direction, the highest probabilistic locations for the hand and leg were an average of 28.26% and 32.03% from the anterior boundary at the upper midbrain level and 30.19% and 33.59% at the lower midbrain level, respectively. We found that the hand somatotopy for the CST is located at the middle portion of the CP and the leg somatotopy is located lateral to the hand somatotopy.

Individual differences in the motivation to communicate relate to levels of midbrain and striatal catecholamine markers in male European starlings

Individuals display dramatic differences in social communication even within similar social contexts. Across vertebrates dopaminergic projections from the ventral tegmental area (VTA) and midbrain central gray (GCt) strongly influence motivated, reward-directed behaviors. Norepinephrine is also rich in these areas and may alter dopamine neuronal activity. The present study was designed to provide insight into the roles of dopamine and norepinephrine in VTA and GCt and their efferent striatal target, song control region area X, in the regulation of individual differences in the motivation to sing. We used high pressure liquid chromatography with electrochemical detection to measure dopamine, norepinephrine and their metabolites in micropunched samples from VTA, GCt, and area X in male European starlings (Sturnus vulgaris). We categorized males as sexually motivated or non-sexually motivated based on individual differences in song produced in response to a female. Dopamine markers and norepinephrine in VTA and dopamine in area X correlated positively with sexually-motivated song. Norepinephrine in area X correlated negatively with non-sexually-motivated song. Dopamine in GCt correlated negatively with sexually-motivated song, and the metabolite DOPAC correlated positively with non-sexually-motivated song. Results highlight a role for evolutionarily conserved dopaminergic projections from VTA to striatum in the motivation to communicate and highlight novel patterns of catecholamine activity in area X, VTA, and GCt associated with individual differences in sexually-motivated and non-sexually-motivated communication. Correlations between dopamine and norepinephrine markers also suggest that norepinephrine may contribute to individual differences in communication by modifying dopamine neuronal activity in VTA and GCt.

Chronic exposure to toluene changes the sleep-wake pattern and brain monoamine content in rats.

Toluene, found in glues and cleaners, is among the inhalants most commonly abused by workers and young drug addicts. In this study, we examined the changes in sleep patterns and monoamine content induced by chronic toluene exposure. Rats were chronically exposed to toluene vapors beginning at 30 days of age for a duration of 30 days. Experiment I was performed in a control group (n=10) and a chronic toluene exposure group (n=10). Rats were implanted with bipolar stainless steel electrodes for electroencephalographic recording (EEG). In experiment II, conducted in two other groups (control and exposed to toluene, n=10 each), animals were sacrificed by decapitation prior to chromatographic analysis. We found that chronic toluene administration affected the organization of sleep patterns and monoamine content. Dopamine (DA) and noradrenaline (NA) increased in the midbrain and striatum. 3,4-dihydroxyphenylacetic acid (DOPAC) increased only in the striatum. Midbrain levels of serotonin (5-HT) increased in the pons and decreased in the hypothalamus and striatum. 5-hydroxyindoleacetic acid (5-HIAA) increased in the pons, midbrain and striatum and decreased in the hypothalamus. Chronic toluene exposure induced changes in the serotonergic and dopaminergic systems and increased SWS and PS deficits. We conclude that toluene exposure disrupts the sleep-wake cycle by affecting the monoaminergic response in cerebral areas related to sleep.

The effects of the perinatal treatment with 5-hydroxytryptophan or tranylcypromine on the peripheral and central serotonin homeostasis in adult rats

Serotonin (5HT) is a biologically active amine present in mammals in the brain and the peripheral tissues. Autism is a neurodevelopmental disorder in which 5HT homeostasis is disturbed both centrally and peripherally, but the relationship between the 5HT disturbances in the two compartments is not understood. In an attempt to explore the relationship between the disturbed peripheral 5HT homeostasis and central 5HT functioning, we exposed the developing rat brain to increased 5HT concentrations, by treatment of rats with subcutaneous injections of the immediate 5HT precursor 5-hydroxy-l-tryptophan (5HTP, 25mg/kg), or the non-selective MAO inhibitor tranylcypromine (TCP, 2mg/kg), during the period of the most intensive development of 5HT neurons – from gestational day 13 to post-natal day 21. The effects of the mentioned treatments on peripheral and central 5HT levels were then studied in adult rats. Platelet and plasma 5HT concentrations (measured by ELISA), as well as cortical and midbrain 5HT, tryptophan and 5-hydroxyindoleacetic acid levels (measured by HPLC) were determined in twelve 5HTP treated and eight TCP treated rats, and compared with the values measured in 10 control, saline treated rats. Treatment with 5HTP significantly raised peripheral but not central 5HT concentrations. At adult age, peripheral 5HT homeostasis was re-established, while modest decrease in 5HT concentration was observed in frontal cortex, presumably due to hyperserotonemia-induced loss of 5HT terminals during brain development. Treatment with TCP induced significant 5HT elevations in both compartments. At adult age, permanent changes in 5HT homeostasis were observed, both peripherally (as hyperserotonemia) and centrally (as altered 5HT metabolism with decreased 5HT concentrations). Further studies are planned in order to explore the nature of the different disturbances of 5HT homeostasis induced by the two compounds, and their results are expected to shed some light on the role of hyperserotonemia in autism.

Improved Assessment of Ex Vivo Brainstem Neuroanatomy With High‐Resolution MRI and DTI at 7 Tesla

The aim of the present work was to provide the topography of the main gray nuclei and white matter tracts of the human brainstem at 7 Tesla (7 T) high-field magnetic resonance imaging (MRI) using structural imaging (T1) and diffusion tensor imaging (DTI). Both imaging techniques represent a new field of increasing interest for its potential neuroanatomic and neuropathologic value. Brainstems were obtained postmortem from human donors, fixated by intracarotid perfusion of 10% neutral buffered formalin, and scanned in a Bruker BioSpec 7 T horizontal scanner. 3D-data sets were acquired using the modified driven equilibrium Fourier transform (MDEFT) sequence and Spin Echo-DTI (SE-DTI) sequence was used for DTI acquisition. High-resolution structural MRI and DTI of the human brainstem acquired postmortem reveals its basic cyto- and myeloar-chitectonic organization, only visualized to this moment by histological techniques and higher magnetic field strengths. Brainstem structures that are usually not observed with lower magnetic fields were now topographically identified at midbrain, pons, and medullar levels. The application of high-resolution structural MRI will contribute to precisely determine the extension and topography of brain lesions. Indeed, the current findings will be useful to interpret future high-resolution in vivo MRI studies in living humans.