All neuropsychological testing and CT exercises were performed at

All neuropsychological testing and CT exercises were performed at the University of Northern British Columbia (UNBC) Brain Research Unit. Informed consent was obtained from individual participants as well as their designated caregiver. All procedures and the collection of data were in accordance with UNBC Research Ethics Board’s policy. Inhibitors,research,lifescience,medical Neuropsychological testing The neuropsychological test battery (Table 2) took less than 90 min to complete. It was constructed to include all major cognitive domains, be a reasonable time period to administer, and ensure a sufficient range of difficulty (floor

and ceiling effects) for participants experiencing cognitive impairments. In addition, the Neuropsychiatric Inventory (Basak Inhibitors,research,lifescience,medical et al. 2008) and the disability assessment for dementia (Cherrier et al. 2001) were also included to provide indices for functions of ability. Table 2 Neuropsychological test administered. Cognitive stimulation training Selleck BMS-907351 Sessions occurred four times per week over a 14-week period, and consisted of approximately two weekly 2-h on-site sessions and two weekly 1-h in-home sessions. On-site testing Inhibitors,research,lifescience,medical at UNBC included: (1) navigation task: participants were provided a standard map of the University and asked to find and return from a marked location on the map. Locations were standardized

so each participant went to the same location during the specified training session. (2) Visuomotor training: (a) a commercially available “Plug and Play” “Pac-Man” game was used for VM training. The

rationale for using Pac-Man is that it requires substantial visually guided ability/control to navigate a virtual environment and it automatically Inhibitors,research,lifescience,medical increases in difficulty as the individual improves in ability. (3) Visuoconstruction procedures: this training required participants to complete three tasks. These tasks included variations Inhibitors,research,lifescience,medical in: block design (WAIS-IV), a correct fold task (Abner et al. 2012), and a mental rotation task (Shepard and Metzler 1988). In-home sessions consisted of workbook activities comprising VS, visuoconstructive, and VM tasks (e.g., “find the differences,” “correct fold tasks,” “mazes,” etc.). Participants were encouraged to engage in these of tasks for a minimum of two weekly sessions of 1 h each week for the duration of the study; 100% compliance was achieved, as measured through weekly tracking sheets. Data analysis Neuropsychological tests Neuropsychological analysis was used to characterize participant’s level of cognitive ability at both pre- and posttraining sessions. The role of this analysis is to track changes in cognitive performance in a population that we would expect to have a progressive decline in overall cognition (Zanetti et al. 1995). Thus, a reduction in cognitive performance would be expected to be observed particularly when the population is tracked over a course of 4–5 months.

Figure 2 Maximum intensity projections (MIPs) of the 3D vascular

Figure 2. Maximum intensity projections (MIPs) of the 3D vascular network in the cat, viewed in (a) coronal (left image) and (b) axial orientations. The axial projection (b) was performed over the full acquisition volume; the coronal projection (a) was produced … Such methods can be used for building models of the vascular network and may benefit a variety of research applications including fMRI, cerebrovascular disease, and cancer angiogenesis. Because of the lengthening T1 and increased SNR, significant gains

can be expected for such studies at even higher magnetic fields such as -~16 to 17T. Inhibitors,research,lifescience,medical At higher magnetic fields such as 14 to 17 T, other unique contrast mechanisms also come into play, leading to exquisite anatomical images obtained using approaches such as phase71 and T2* -weighted imaging, providing unprecedented visualization of anatomy in animal models.72 The mechanism responsible for this improved anatomical imaging appears to be tissue-specific differences induced largely by myelin content Inhibitors,research,lifescience,medical and/or presence of iron.73-77 Thus, the primary advantage of ultrahigh field for structural MRI is not just the SNR gain, which could be Inhibitors,research,lifescience,medical traded

for increased spatial resolution at constant imaging times or imaging time at constant spatial resolution, but also gains in contrast mechanisms. A recent and exciting example where the advantages of combined Inhibitors,research,lifescience,medical use of high magnetic fields and animal models were indispensable in morphological imaging has been the in vivo detection of amyloid plaques78,79 (Figure 3) exploiting the genetic capabilities available in animal models. Among the neurodegenerative disorders, Alzheimer’s disease has received much of the attention due to its frequency and hence high public health impact. Aβ plaques, a cardinal

pathologic feature of Alzheimer’s disease, were previously observed In T2* -weighted images of ex vivo tissue specimens taken from the Inhibitors,research,lifescience,medical brain of AD mice. These plaques were imaged for the first time in vivo in anesthetized AD mice in reasonable imaging times (~ 1 hour)78 using T2 weighting at very high magnetic fields (9.4 T), incorporating strategies that minimize perturbations originating from breathing and brain pulsation. The mechanism responsible for this accomplishment is thought to be alterations in effective T2 by diffusion-induced dynamic averaging of magnetic susceptibility Sitaxentan gradients around the plaques. This contrast is small but FK506 in vivo depends quadratically on magnetic field magnitude. As such, the ultrahigh field was indispensable. Imaging of labeled plaques has been accomplished with other non-MR modalities (see references in ref 78). Unlike other modalities, however, MRI provides the potential for visualizing individual plaques noninvasively. Figure 3. 9.4 T MRI and histology of 24 6-month 6-old AD mouse.

16,17 Among the large variety of chemical messengers acting in ne

16,17 Among the large variety of chemical messengers acting in nerve cell signaling, 5-HT is the focus of much interest due to its implication in almost every physiological function (eating, reward, thermoregulation, cardiovascular regulation, locomotion, pain, reproduction, sleepwake cycle, memory, cognition, aggressiveness, responses to stressors,

emotion, and mood) and in several human pathologies. Thus, dysfunction Inhibitors,research,lifescience,medical of the serotonergic AZD1480 molecular weight systems is thought to be associated with irritable bowel syndrome,18 restless legs syndrome,19 sudden infant death syndrome,20,21 autism,22 headache,23 insomnia,24 anxiety,25 depression,26 anorexia,27,28 schizophrenia,29 Parkinson’s disease,30 and Alzheimer’s disease.31,32 At the present time, most of the anxiolytic/antidepressant compounds such as tricyclic and tetracyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs),33,34 azapirones,35 setron antiemetics,36

and triptans used to relieve migraine,37 all target the serotonergic systems. Besides a well-known Inhibitors,research,lifescience,medical dopaminergic component, atypical neuroleptics (eg, olanzapine, clozapine, quetiapine, aripiprazole) interact with serotonergic receptors (ie, 5-HT1A, Inhibitors,research,lifescience,medical 5-HT2A-2C, 5-HT6 and 5-HT7).38-40 Finally, psychotropic drugs including LSD, mescaline, cocaine, and amphetamines powerfully alter 5-HT functions via 5-HT1A, 5-HT2A receptors41,42 and monoaminergic transporters.43-45 Inhibitors,research,lifescience,medical 5-HT is massively synthesized in the gastrointestinal

tract (mainly in enterochromafin cells), whereas only a small percentage is produced within the nervous system.46,47 There is some evidence that 5-HT synthesis, release by calcium-dependent exocytosis, selective reuptake by an energy-dependent membrane transporter, metabolism and reuptake in vesicles operate in all the neuronal elements of the 5-HT neurons (ie, soma, dendrites, axons, and terminals), together participating in 5-HT homeostasis.48,49 The widespread distribution of 5-HT axons and terminals Inhibitors,research,lifescience,medical throughout the neuraxis (Figure TCL 1), the frequent nonsynaptic neurotransmission (called diffuse or volume neurotransmission 48,50-52), as well as the abundance of 5-HT receptors (Table I) contribute to explaining the complex relationships between 5-HT and other neurotransmitter and neurohormonal systems. Figure 1. Schematic sagittal view of the human brain showing the distribution of the serotonergic systems. The raphe nuclei containing the majority of the serotonergic cell bodies appear in purple. It is readily seen that these nuclei are exclusively located in … Table I Table I. Serotonin (5-HT) receptors in the human brain: distribution, putative functions, and related pathologies. Pre-RNA *splicing and ° editing variants. For review see also refs 98 to100. X, dorsal motor n of the vagus nerve; ACN, accumbens …

We also investigated the association between noncontinuous use an

We also investigated the association between noncontinuous use and relapse or recurrence within 1 year of starting treatment and the factors associated with noncontinuous antidepressant use. Material and Methods Study design, source of data, and patient population This retrospective cohort study was conducted in the Prince of Wales Hospital (PWH) in Shatin, Hong Kong. The study was approved by the Joint Chinese University

of Hong Kong and New Territories East Cluster Inhibitors,research,lifescience,medical (CUHK-NTEC) Clinical Research Ethics Committee (CREC) in July 2008. Eligible patients were identified through data retrieval using the Clinical Data Analysis and Reporting System (CDARS). This centralized-computerized database stores longitudinal clinical information including patient demographics, prescription, and dispensing records, and diagnosis patients

received from all public hospitals in Hong Kong. Patients were included if Inhibitors,research,lifescience,medical (1) he or she was aged >18 years, (2) was attending Psychiatric Specialist Outpatient Clinic (SOPD) of PWH during the period between 1st January 2006 to 31st December 2007, (3) had an antidepressant dispensed during the study period, and Inhibitors,research,lifescience,medical (4) were diagnosed with major depressive disorders according to the International Classification of Disease-10 classification of mental and behavioral disorders. Subjects were excluded if they had (1) concurrent diagnosis Inhibitors,research,lifescience,medical of bipolar disorder, obsessive-compulsive disorder, psychosis, schizophrenia, substance abuse, post-traumatic stress disorder, acute stress disorder, and panic

disorders, or (2) a diagnosis of dementia or mental retardation, or (3) a prescription of antidepressants 6 months prior to the study period, or (4) documented concurrent psychiatric-related follow-ups in other health care settings (where they may also had been prescribed antidepressants), or 5) history of drug overdose or suicide. If there were more than one period of antidepressant use during the study period, Inhibitors,research,lifescience,medical only the first episode was counted. Electronic patient records were then reviewed to confirm the eligibility. Further information regarding the antidepressant use and relapse and recurrence after treatment initiation was supplemented by reviewing the written medical records. Data collection A standard form was designed for collecting ADAMTS5 patient-, illness- and treatment-related parameters. These included demographics such as age, gender, type of accommodation (as an indirect indictor for socioeconomic status) and marital status. Details of treatment regimen including drug name, dosage, frequency, duration, and prescription refill pattern were documented. Other treatment-related factors such as the frequency of follow-up were also recorded.

Epidemiological assessments indicates that in south Italy the lat

Epidemiological assessments indicates that in south Italy the late-onset forms of Pompe disease are largely under-diagnosed. In fact, with an estimated frequency of one

in 56000 in Caucasian populations late-onset cases should be about 100 in the 6×103 inhabitants of the Campania, but after a recognition at all the Centers Inhibitors,research,lifescience,medical specialized for neuromuscular diseases of this region, in June 2011, at the time of the present Meeting, less than 10 genetically proofed patients result to be followed up. With these premises the team of neuromuscular disorders specialists at the Department of Neurology directed by professor Giuseppe Di Iorio, together with the team of Cardiomyology and Medical Genetics, directed by professor

Giovanni Nigro and professor Luisa Inhibitors,research,lifescience,medical Politano of the Second University of Naples, have organized the meeting “A network for Pompe disease treatment. Genetic Myopathy of children and adults” held in Naples, Italy, on June the 13th, 2011. Specific aims of the meeting were: to perform a comprehensive review from a multidisciplinary point of view on basic knowledge and new developments on clinic, diagnosis and management of Pompe disease; to discuss personal experiences with the management of Pompe disease between clinical trial experts in clinical and laboratory diagnosis, treatment, and Inhibitors,research,lifescience,medical management, including, cardiac, respiratory, gastrointestinal/nutritional, muscoloskeletal, neurological, supportive Inhibitors,research,lifescience,medical and rehabilitative care, anaesthesiology, general medicine, psychosocial, issues. The meeting addressed to University and Hospital doctors, practitioners and doctors in training in all branches potentially involved in diagnosis, therapy and management of Pompe patients had more than 100 registered participants. The Meeting

will benefit of the contributions Inhibitors,research,lifescience,medical of speakers of international scientific level, such as Corrado Angelini, from the University of Padua, who first described along with Engel AG, variable levels of α-GA in muscle and leukocytes of patients with Pompe disease, Antonio Toscano, from the University of Messina, Coordinator of the Italian Group for the Study of Glycogenosis, who will report on the Italian guidelines Farnesyltransferase and the activities of the Italian centers for the treatment of Pompe disease, Generoso Andria, from the University of Naples, Coordinator of the Reference Center for Rare Diseases of the Campania region, who first treated with alglucosidase alpha an Italian patient with classic infantile Pompe disease and will speake about the role of the pediatrician in the infantile form of Pompe disease. Furthermore, all important topics in clinics, diagnosis and treatment of Pompe disease, such as the therapeutic strategies alternatives to ERT, will be discussed by several experts from the universities and some hospitals of Naples and the Campania region.

The strength of each node is defined as its average connectivity

The strength of each node is defined as its average connectivity with all

other nodes, and the graph’s size is defined by the number of nodes in the largest connected component; a larger graph size indicates fewer disconnected nodes.66,67 Accumulating evidence suggests that the small-world topological properties of brain functional networks are altered in patients with schizophrenia. In one study, in 31 patients with schizophrenia compared with 31 healthy controls, functional connectivity between 90 cortical and subcortical regions was AZD2014 research buy estimated by partial correlation Inhibitors,research,lifescience,medical analysis and thresholded to construct a set of unidirected graphs.68 The healthy subjects demonstrated efficient small-world properties, whereas topological parameters of brain networks — strength and degree of connectivity — were decreased in patients with schizophrenia, especially in the prefrontal, parietal, and temporal lobes, consistent with a hypothesis of dysfunctional integration. In another study, in a sample of 203 patients with schizophrenia, Inhibitors,research,lifescience,medical compared with 259 healthy controls, multimodal network organization was noted to be abnormal, as measured by topological and

distance metrics of anatomical network organization, abstracted from Inhibitors,research,lifescience,medical fMRI data.69 Patients with schizophrenia, compared with controls, demonstrated reduced hierarchy throughout the small-world regime, and increased connection distance in the multimodal cortical network. The loss of frontal hubs and the emergence of nonfrontal Inhibitors,research,lifescience,medical hubs was also noted,

supporting the hypothesis of schizophrenia as a dysconnectivity syndrome, impacting the efficiency of a frontally dominated hierarchical network of multimodal cortical connections. Inhibitors,research,lifescience,medical Though the impact of genetic variation on network topology based on graph analyses has not yet been reported, moderate levels of heritability have been found for brain graph topology measured in a twin study using EEG, suggesting that genetic variation may Impact small-world organization and brain graph metrics.70 The next wave of imaging genetics: polygenic risk Just as imaging genetics will continue to incorporate increasingly sophisticated analytic methodologies, so too will imaging genetics evolve to incorporate increasingly sophisticated models of genetic risk, 4��8C reflective of the increasingly apparent polygenic complexity of psychiatric syndromes. Genome-wide association studies (GWAS) have indicated a highly significant polygenic component of schizophrenia risk, possibly involving up to thousands of common alleles of very small effect, at the population level.71 While early imaging genetics used intermediate phenotypes to assess the impact of single gene variants, recent studies have increasingly tended towards epistatic models of gene interaction.

Yet another distinguishing feature described by Haller and Vissin

Yet another distinguishing feature described by Haller and Vissing is the opposite effect of glucose administration in the two diseases. Patients with McArdle disease benefit from glucose administration or from a sucrose load before exercise (9) because their metabolic block, which is far upstream in carbohydrate metabolism, impairs glycogen but not glucose utilization (Fig. ​(Fig.3).3). In contrast, meals rich in carbohydrate exacerbate the exercise intolerance of patients with phosphofructokinase (PFK)

deficiency for two reasons: (i) due to the metabolic block downstream in glycolysis, their muscle cannot utilize either glycogen or glucose; (ii) Inhibitors,research,lifescience,medical glucose decreases the blood concentration of the alternative fuels FFA and ketones, Inhibitors,research,lifescience,medical a situation dubbed the “out of wind” phenomenon (10). In 1980, while studying two patients with PFK deficiency, we noted, much to our surprise, that their muscle biopsies showed, in addition to deposits of normal-looking glycogen,

pockets of an abnormal polysaccharide with the histochemical and ultrastructural features of polyglucosan (11): the polysaccharide was intensely PAS-positive Inhibitors,research,lifescience,medical but only partially digested by diastase and, in the electron microscope, consisted of finely granular and 3-MA order fibrillar material, similar to the amylopectin-like storage material of GSD IV (branching enzyme deficiency). Based on experiments in E. coli (12), we reasoned that the high concentration of glucose 6 phosphate (G6P) resulting from the metabolic block would activate glycogen synthetase abnormally and alter the normal Inhibitors,research,lifescience,medical ratio of glycogen synthetase (GS) to branching enzyme (BE) to the advantage of GS, thus favoring the synthesis of polysaccharide with excessively long and poorly ramified chains (polyglucosan). In a serendipitous but spectacular

experiment, Raben et al. verified this mechanism when they overexpressed GS in the muscle of transgenic mice lacking acid maltase and observed massive accumulation of polyglucosan (13). The Inhibitors,research,lifescience,medical crucial role of the GS/BE ratio in the synthesis of normal glycogen has been confirmed in other conditions, such as cardiac glycogenoses due to defects in AMP-dependent protein kinase (AMPK) (14) and, possibly, in Lafora disease (this issue). The pathogenesis of rhabdomyolysis and myoglobinuria in McArdle CYTH4 disease, as in other glycogenoses, remains unclear. There is no doubt that the block of aerobic glycolysis or, sometimes, anaerobic glycolysis during intense exercise results in an “energy crisis”. However, neither old biochemical determinations in muscle biopsies taken during an exercise-induced contracture (15) nor more recent 31P magnetic resonance spectroscopic studies during controlled exercise (1, 16) have ever revealed a critical decrease of ATP.

The first systematic discussion of the relationship between physi

The first systematic discussion of the relationship between physical and psychological stress dates back to World War I. The history of that discussion provides an informative context for current controversies concerning PTSD and TBI.1 Combat techniques in World War I introduced new types of combat stress that had not existed during previous wars. Soldiers engaged in trench warfare were relatively immobile and therefore more vulnerable. They were also chronically exposed to new and perversely Inhibitors,research,lifescience,medical lethal threats, such as poison gas, machine gun fire, mortar attacks, land mines, and tanks.

Casualties were devastating, and fatality rates were frightening. Men watched their friends die beside them, and they confronted Inhibitors,research,lifescience,medical the possibility of their

own demise on a daily basis. Alternatively they might be maimed and consigned to a life of chronic disability. As the war progressed, the high casualty rate made it clear that. Britain and continental European countries were losing many of an entire generation of young men―a Tyrphostin AG-1478 social loss from which they would be slow to recover. This sense of futility and despair was eloquently expressed by British war poets such as Wilfred Owen and Siegfried Sassoon: Earth’s wheels run oiled with blood. Forget we that. Let us lie down and dig ourselves in thought. Beauty is yours and you have mastery. Inhibitors,research,lifescience,medical Wisdom is mine, and I have mystery. We two will stay behind and keep our troth. Let us forego men’s minds that are brute’s natures, Let us not sup the blood which some say nurtures, Be we not swift with swiftness of the tigress. Let us break ranks from those who trek from progress. Miss Inhibitors,research,lifescience,medical we the march of this retreating world Into

old citadels Inhibitors,research,lifescience,medical that are not walled. Let us lie out and hold the open truth. Then when their blood hath clogged the chariot wheels We will go up and wash them from deep wells. What though we sink from men as pitchers falling Many shall raise us up to be their filling Even from wells we sunk too deep for war Even as one who bled where no wounds were. Wilfred Owen Strange Meeting Project Gutenberg Etext of Poems by Wilfred Owen In this context of brutal bloodshed and omnipresent fear, a new and somewhat unfamiliar type of disability emerged that had not been described in previous wars: a syndrome characterized by confusion, memory impairment, 17-DMAG (Alvespimycin) HCl headache, difficulty concentrating, tremor, and sensitivity to loud noises. This was initially assumed to be due to exposure to explosions, leading to concussions of the brain (“commotion cerebri”) in the absence of visible signs of external head trauma, and the disorder began to be referred to as “shell shock.” Postmortem examination of two cases revealed a variety of abnormalities, particularly vascular damage and congestion.2 As the war progressed, the number of shell shock casualties grew alarmingly.

147,148 Stimuli that entail an increase in neuronal activity have

147,148 Stimuli that entail an increase in neuronal activity have been shown to stimulate neurogenesis and enhance survival of new neurons in the adult mammalian hippocampus.149 The incorporation of functional adult-generated neurons into existing neural networks provides higher capacity for plasticity, while they favor the encoding and storage of certain types of memories.150-152 Although neurogenesis continues throughout life, its rate declines with increasing age,153,154 and the proportion of Inhibitors,research,lifescience,medical neuronal stem cells that survive to become mature neuronal ceils is reduced.155 This

may be due to intrinsic decline in neuronal stem cell responsiveness to stimulating environmental cues, to a decrease in or disappearance of these environmental cues, or to accumulation of inhibitory factors.156 Intrinsic properties of neural progenitor cells such as gene transcription and telomere activity change with age, Inhibitors,research,lifescience,medical which may contribute to decline in neurogenesis. While most studies indicated a correlation between decreased Inhibitors,research,lifescience,medical hippocampal neurogenesis and impaired performance in hippocampus-dependent ATM Kinase Inhibitor cognitive tasks in age mice, few have demonstrated that young and aged mice are equivalent in their cognitive ability. The lack of neuronal ability to divide may be overcome by replacing damaged neurons or

by restoring their function. Thus, Kittappa et al157 revisited the molecular mechanisms responsible for neuronal renewal from stem cells, which are present in specific niches within the adult brain. The authors provided the novel notion that even non-terminaliy Inhibitors,research,lifescience,medical differentiated neural stem cells play roles in the regeneration of neurons and their synaptic Inhibitors,research,lifescience,medical function by mechanisms beyond mere cell replacement. These cells signal specific survival pathways that are worth investigating

in search for novel therapeutic strategies against neurodegeneration. According to this notion, noninvasive tools to follow up synaptic function in the living brain are therefore essential for our better understanding of neuronal regeneration. Although neuronal turnover is reduced in every neurogenic region of the aged brain, neuronal precursor cells clearly survive, remain responsive to growth factors and other physiological Nature Methods stimuli, and can increase their activity in response to damage.157 Exploration of the regulation of neuronal progenitor cells in the aging brain is critical not only for understanding age-related cognitive deficits, but also for progress toward the goal of using the brain’s regenerative potential to restore functional loss. Dysregulated or impaired neurogenesis may compromise plasticity and neuronal function in the hippocampus and other neuronal systems, and exacerbate neuronal vulnerability.

In vivo imaging allows regional analyses (from the whole brain to

In vivo imaging allows regional analyses (from the whole brain to groups of neurons), whereas electron microscopy provides images … Cellular mapping of 5-HT-producing neurons in the CNS Due to the postmortem instability of 5-HT118 and other possible methodological bias,119 quantitative biochemical estimation of 5-HT in the human brain subdivisions should be interpreted with caution, as illustrated by the numerous discrepant data reported since the 1950s. For the same reason, morphological approaches by formaldehyde-induced fluorescence or immunohistochemistry using antibodies

against 5-HT are limited to biopsies and fetal brain tissues. Most Inhibitors,research,lifescience,medical of the anatomical studies in human are based on regional autoradiography of SERT binding sites to selective radioligands and immunohistochemical Inhibitors,research,lifescience,medical studies using antibodies against TPOH, which represent more stable postmortem markers. Therefore, from these studies and those performed in much detail in other species including rodents,120 cat,121 and nonhuman primates,122 it appears that the anatomy of the serotonergic system has remained somewhat similar between different species of mammals. The 5-HT systems belong to the neuronal systems composed of a restricted number of neurons emitting extensively branched, non- or poorly myelinated axons that innervate almost all brain nuclei. As first described

in human fetuses123,124 and later Inhibitors,research,lifescience,medical in adults by several authors,125-129 the distribution of the 5-HT cell bodies (approximately 350 000 cells) in the human brain is restricted to the brain stem. As illustrated in Figure 1, a large majority of them is concentrated along the midline in the raphe nuclei, extending from the caudalmost level Inhibitors,research,lifescience,medical of the medulla oblongata to mid-level of mesencephalon, but Inhibitors,research,lifescience,medical a substantial number is located in the reticular formation

lateral to these nuclei. The 5-HT neurons form a continuum of cells with loosely defined boundaries along the raphe nuclei. On the basis of studies of cell body localization and their respective projections, the 5-HT neurons can be separated into two groups: a rostral group located in the mesencephalic and rostral pons, sending axons to the forebrain, and a caudal group lying in the rostral pons and medulla oblongata, sending axons in the brain stem and spinal cord (refs in ref 128) In humans, the rostral group contains approximately 85% of the 5-HT neurons. It is composed of neurons located in four DZNeP cell line nuclei and one area, namely the interpeduncular, Microbiology and Molecular Biology Reviews the caudal linear, the dorsal raphe (DRN with 165 000 neurons) and the median raphe (MRN with 64 000 neurons) nuclei. The additional area corresponds to the caudal mesencephalic and rostral pontine reticular formation. 5-HT neurons spread in this area were already observed in the rat and cat species and their large number estimated in human (60 000 neurons). The caudal group accounts for 15% of all the 5-HT neurons.