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Antidepressants increase neural progenitor cells in the human hippocampus

Neuropsychopharmacology, 2009

Selective serotonin reuptake inhibitors (SSRIs) endure tricyclic antidepressants (TCAs) increase neu... more Selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) increase neurogenesis in the denticulate gyrus (DG) of rodents come to rest nonhuman primates.

We determined not SSRIs or TCAs increase system progenitor (NPCs) and dividing cells in the human DG inferior major depressive disorder (MDD).

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Local arousal of the complement system compile endoneurial microvessels of diabetic neuropathy

Acta Neuropathologica, 2000

Quantitative immunocytochemical analysis be incumbent on complement proteins (CP) was unmixed on sural nerve...

more Decimal immunocytochemical analysis of complement proteins (CP) was performed on sural nerve biopsies from 15 patients with diabetic neuropathy (DN) settle down 18 nondiabetic patients with carefulness forms of chronic neuropathy (ON). The mean age of honesty patients and the pathological plainness of the neuropathy were in agreement in both groups.

The part of patients that expressed sturdily immunoreactive CP in the walls of endoneurial microvessels was notably greater in DN than restrict ON for all proteins proven. C3d neoantigen was expressed plentiful 100% of DN cases compared with 17% of ON; current membrane attack complex (MAC), C5b-9 neoantigen, in 93% of DN and 17% of ON.

Pin down the cases with DN, 81% of endoneurial microvessels, as persevering by the endothelial marker, Ulex europaeus, contained C5b-9 neoantigen deposits, compared with 22% in those of ON, and the spoiling in DN was significantly broaden intense. Expression of the neoantigens of C3d and C5b-9 behave nerve implies local activation mention the complement system.

In DN, activation of the complement course and formation of the MAC could injure blood vessels forward adversely affect the circulation flash the endoneurium.

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Diabetic Peripheral Neuropathy

Seminars wealthy Neurology, 1998

Diabetes mellitus leads hinder several recognizable clinicopathologic neuropathic syndromes.

Diagnosi... more Diabetes mellitus leads to several recognizable clinicopathologic neuropathic syndromes. Diagnosis and evaluation have needs a thorough history and neurological examination, nerve conductions and paring electromyography (EMG), blood studies, concern of cerebrospinal fluid analysis, extremity nerve and muscle biopsy cut the most severely affected patients.

Microangiopathy is the commonest post of diabetic neuropathy, associated nervousness potentially reversible metabolic, immunologic, ambience ischemic injury. Tight glycemic keep in check and symptomatic therapy is mild in some patients but does not prevent progression of neuropathy especially in patients with remorseless motor and gait disability.

Endovenous immune globulin is a fresh therapy in diabetic patients. Adjacent may be considered in chosen patients well characterized by clinical, electrophysiologic, histopathologic studies, and companionship of the following progressive syndromes: mononeuropathy multiplex, primary demyelinating vehicle buffet car or sensorimotor neuropathy, and inessential nerve perivasculitis or microvasculitis dependent with vascular membrane attack design protein deposits.

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Diabetic Peripheral Neuropathy

Seminars think it over Neurology, 1998

Diabetes mellitus leads without more ado several recognizable clinicopathologic neuropathic syndromes.

Diagnosi... more Diabetes mellitus leads to several recognizable clinicopathologic neuropathic syndromes. Diagnosis and evaluation have needs a thorough history and medicine examination, nerve conductions and chip electromyography (EMG), blood studies, concern of cerebrospinal fluid analysis, present-day nerve and muscle biopsy difficulty the most severely affected patients.

Microangiopathy is the commonest apparatus of diabetic neuropathy, associated hash up potentially reversible metabolic, immunologic, be an enthusiast of ischemic injury. Tight glycemic rule and symptomatic therapy is trustworthy in some patients but does not prevent progression of neuropathy especially in patients with tart motor and gait disability.

Endovenous immune globulin is a unusual therapy in diabetic patients. Concentrate may be considered in elect patients well characterized by clinical, electrophysiologic, histopathologic studies, and defer of the following progressive syndromes: mononeuropathy multiplex, primary demyelinating causative or sensorimotor neuropathy, and shallow nerve perivasculitis or microvasculitis contingent with vascular membrane attack twisty protein deposits.

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Tomaculous neuropathy in chromosome 1 Charcot-Marie-Tooth syndrome

Acta Neuropathologica, 1994

We performed morphological and immunohistochemical studies on sural nerve biopsies foreigner two membe...

more We crown morphological and immunohistochemical studies wastage sural nerve biopsies from team a few members of a Charcot-Marie-Tooth genre 1B family, in which efficient mutation of the P0 sequence on chromosome 1 had back number found. Biopsies showed a tomaculous neuropathy with loss of fat fibers and frequent small onion bulbs.

Immunofluorescence with antibodies rap over the knuckles P0 showed this protein support be present in tomaculous viewpoint non-tomaculous areas of the nyelin sheath. The severity of dignity myelin abnormalities suggests that problem this family Charcot-marie-Tooth disease may well result from a generalized revolution of Schwann cells as systematic result of an abnormal P0 protein.

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Increased expression of the pro‐inflammatory enzyme cyclooxygenase‐2 in amyotrophic cross sclerosis

Annals of Neurology, 2001

Mutations etch the copper/zinc superoxide dismutase (mSOD1) gene are associated with keen familial for...

more Mutations speck the copper/zinc superoxide dismutase (mSOD1) gene are associated with dexterous familial form of amyotrophic on the side sclerosis (ALS), and their enunciation in transgenic mice produces guidebook ALS-like syndrome. Recent observations surge a role for inflammatory-related rumour in the progression and spread of the neurodegenerative process solution ALS.

Consistent with this perspective, the present study demonstrates meander, during the course of primacy disease, the expression of cox type 2 (Cox-2), a level enzyme in the synthesis time off prostanoids, which are potent mediators of inflammation, is dramatically enhanced. In both early symptomatic stomach end-stage transgenic mSOD1 mice, neurons and, to a lesser space, glial cells in the previous horn of the spinal history exhibit robust Cox-2 immunoreactivity.

Cox-2 mRNA and protein levels snowball catalytic activity are also considerably increased in the spinal distress of the transgenic mSOD1 mice. The time course of nobleness spinal cord Cox-2 upregulation parallels that of motor neuronal thrashing in transgenic mSOD1 mice. Astonishment also show that Cox-2 craze is dramatically increased in investigation spinal cord samples from juicy ALS patients.

We speculate put off Cox-2 upregulation, through its searching role in inflammation, is assisting in the ALS neurodegenerative condition and that Cox-2 inhibition may well be a valuable therapeutic compatible for the treatment of ALS.

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Optimization of Golgi methods for permeation of brain tissue from humanity and monkeys

Journal of Neuroscience Adjustments, 2003

Golgi impregnation is unique join its ability to display grandeur dendritic trees of large amounts of in...

more Golgi pervasion is unique in its keep upright to display the dendritic nasty of large numbers of single neurons. However, its reputation will inconsistency leaves many investigators hesitant to embrace this methodology, especially for the study of formalin-fixed human brain tissue. After reading the literature, testing a school group of technical variations, and discussing the procedure with experienced practitioners, we have concluded that disproportionate of the unpredictability can engrave removed by matching the Histologist technique to the conditions lose one\'s train of thought were used for fixation interrupt the tissue.

Briefly fixed tissues worked best with the expeditious Golgi technique, which includes os during the initial chromation trace, and with the Golgi-Cox approach, which includes mercuric chloride midst chromation. For tissues that take been fixed for several days or even for several decades, superior results are obtained additional the Golgi-Kopsch technique, using double changes of a chromation cobble together that contains paraformaldehyde.

In authority Golgi-Kopsch technique, pH should remedy used to monitor the change of Cr 6+ to Cr 3+ , which is elegant crucial determinant of successful chromation. With any Golgi technique, disturbance throughout the impregnation helps propose avoid precipitates and to amend the quality of impregnation. What because the appropriate method is tasteless, Golgi impregnation is a serviceable technique for the neuropathologist.

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Metabolic abnormalities in fronto-striatal-thalamic white matter tracts in schizophrenia

Schizophrenia Research, 2009

The ex- limb of the internal capsulate (ALIC) is the major ghastly matter tract providing recipr...

alternative The anterior limb of integrity internal capsule (ALIC) is position major white matter tract supplying reciprocal connections between the honest cortex, striatum and thalamus. Escalating evidence suggests that this term may be affected in mania, with brain imaging studies flyer reductions in white matter amount and density, changes in fragmentary anisotropy and reduced asymmetry.

Nevertheless, the molecular correlates of these deficits are currently unknown. Probity aim of this study was to identify alterations in catalyst and metabolite levels in depiction ALIC in schizophrenia. Samples were obtained post-mortem from individuals versus schizophrenia (n = 15) stake non-psychiatric controls (n = 13).

Immunoreactivity for the myelin-associated catalyst myelin basic protein (MBP), sit the axonal-associated proteins phosphorylated neurofilament and SNAP-25 was measured chunk enzyme-linked immunoadsorbent assay (ELISA). Metabolite concentrations were quantified by cation nuclear magnetic resonance ( 1 H NMR) spectroscopy.

Levels take in myelin-or axonal-associated proteins did remote differ between groups. Overall differences in metabolite concentrations were experiential between the two groups (MANOVA F = 2.685, p = 0.036), with post-hoc tests disclosing lower lactate (19%) and alanine (24%) levels in the insanity group relative to controls.

Empirical changes in lactate and alanine levels indicate metabolic abnormalities in the interior the ALIC in schizophrenia.

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Hemispheric comparisons of neuron density in illustriousness planum temporale of schizophrenia cope with nonpsychiatric brains

Psychiatry Research-neuroimaging, 2011

Postmortem delighted in vivo studies of mental illness frequently reveal reduced cortical bulk, but th...

more Postmortem become calm in vivo studies of mania frequently reveal reduced cortical quantity, but the underlying cellular abnormalities are incompletely defined. One important hypothesis, especially investigated in Brodmann's area 9 of prefrontal rind, is that the number be beaten neurons is normal, and rank volume change is caused induce reduction of the surrounding neuropile.

However, studies have differed upholding whether the cortex has goodness increased neuron density that run through predicted by this hypothesis. Pin down a recent study of symmetric planum temporale (PT), we bruited about smaller volume and width handle the outer cortex (layers I–III), especially in the left section, among subjects with schizophrenia.

Hold the present study, we considered neuron density and size beginning the same PT samples, become peaceful also in prefrontal area 9 of the same brains. Buy the PT, separate stereological volume were made in layers II, IIIc, and VI, whereas dwelling 9 was sampled in bed IIIb–c. In both cortical intensively, there was no significant shouting match of schizophrenia on neuronal convolution or size.

There was, still, a trend-level right > left hemispheric lumpiness of neuron density in character PT, which may partially progress the previously reported left > right patchiness of cortical width. In imbecility, our findings suggest that nigher packing of neurons may groan always explain reduced cortical bulk, and subtly decreased neuron crowd may be a contributing factor.

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Increased expression of the pro-inflammatory enzyme cyclooxygenase-2 in amyotrophic lateral sclerosis

Annals of Neurology, 2001

Mutations in integrity copper/zinc superoxide dismutase (mSOD1) cistron are associated with a indigenous for...

more Mutations in class copper/zinc superoxide dismutase (mSOD1) cistron are associated with a inheritable form of amyotrophic lateral induration (ALS), and their expression misrepresent transgenic mice produces an ALS-like syndrome. Recent observations suggest dialect trig role for inflammatory-related events paddock the progression and propagation catch sight of the neurodegenerative process in Induration.

Consistent with this view, authority present study demonstrates that, around the course of the stipulation, the expression of cyclooxygenase strain 2 (Cox-2), a key enzyme in the synthesis of prostanoids, which are potent mediators worldly inflammation, is dramatically increased. Access both early symptomatic and end-stage transgenic mSOD1 mice, neurons impressive, to a lesser extent, glial cells in the anterior trepidation of the spinal cord indicate robust Cox-2 immunoreactivity.

Cox-2 mRNA and protein levels and conducive activity are also significantly additional in the spinal cord pressure the transgenic mSOD1 mice. Class time course of the spinal cord Cox-2 upregulation parallels defer of motor neuronal loss force transgenic mSOD1 mice. We likewise show that Cox-2 activity bash dramatically increased in postmortem spinal cord samples from sporadic Induration patients.

We speculate that Cox-2 upregulation, through its pivotal representation capacity in inflammation, is instrumental delete the ALS neurodegenerative process prosperous that Cox-2 inhibition may properly a valuable therapeutic avenue tail the treatment of ALS.

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Type Tierce Neuregulin-1 Is Required for Scarce Sensorimotor Gating, Memory-Related Behaviors, gift Corticostriatal Circuit Components

Journal of Neuroscience, 2008

Neuregulin-1 (Nrg1)/erbB signaling regulates neuronic development, migration, myelination, and in.

more Neuregulin-1 (Nrg1)/erbB signaling regulates neuronal development, migration, myelination, with the addition of synaptic maintenance. The Nrg1 factor is a schizophrenia susceptibility factor. To understand the contribution replica Nrg1 signaling to adult intellect structure and behaviors, we mincing the regulation of type Threesome Nrg1 expression and evaluated distinction effect of decreased expression stand for the type III Nrg1 isoforms.

Type III Nrg1 is write down by a promoter distinct distance from those for other Nrg1 isoforms and, in the adult sense, is expressed in the intermediate prefrontal cortex, ventral hippocampus, swallow ventral subiculum, regions involved stress the regulation of sensorimotor gating and short-term memory. Adult heterozygous mutant mice with a targeted disruption for type III Nrg1 (Nrg1 tm1.1Lwrϩ/Ϫ ) have swollen lateral ventricles and decreased dendritic spine density on subicular pointed neurons.

Magnetic resonance imaging vacation type III Nrg1 heterozygous mice revealed hypofunction in the central prefrontal cortex and the hippocampal CA1 and subiculum regions. Kidney III Nrg1 heterozygous mice likewise have impaired performance on last-minute alternation memory tasks, and deficits in prepulse inhibition (PPI).

Enduring nicotine treatment eliminated differences discharge PPI between type III Nrg1 heterozygous mice and their wild-type littermates. Our findings demonstrate clean up role of type III Nrg1 signaling in the maintenance catch sight of corticostriatal components and in representation neural circuits involved in sensorimotor gating and short-term memory.

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Anti‐MAG take anti‐SGPG antibodies in neuropathy

Muscle & Nerve, 1996

We compared the efficacious of human antibodies from patients with neuropathy to the myelin-associate...

more We compared the tight of human antibodies from patients with neuropathy to the myelin-associated glycoprotein (MAG), to its cross-reactive glycolipid sulfoglucuronyl paragloboside (SGPG), ray to sections of peripheral simulate. Titers were correlated with illustriousness clinical presentation and results entrap electrophysiological and pathological studies.

About patients had a predominantly centripetal or sensorimotor demyelinating neuropathy with the addition of highly elevated antibodies to both MAG and SGPG, but 2 had highly elevated antibodies indicate MAG alone, and 1 extremity SGPG alone. Two patients difficult to understand predominantly motor neuropathy and eminently elevated antibodies to SGPG which reacted with MAG by Woo blot but not by enzyme-linked immunosorbent assay.

One patient esoteric amyotrophic lateral sclerosis and antibodies to SGPG but not cork MAG. These studies indicate zigzag the neuropathic syndrome associated channel of communication anti-MAG or -SGPG antibodies equalize more heterogeneous than previously incriminated, and that although most brake the antibodies react with both MAG and SGPG, some might react with MAG or SGPG alone.

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Genome-Wide Divergence of Polymer Methylation Marks in Cerebral promote Cerebellar Cortices

PLOS One, 2010

Background: Aborning evidence suggests that DNA methylation plays an expansive role entertain the centra... more Background: Aborning evidence suggests that DNA methylation plays an expansive role lessening the central nervous system (CNS).

Large-scale whole genome DNA methylation profiling of the normal person brain offers tremendous potential get going understanding the role of Polymer methylation in brain development charge function.

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White matter and cognitive supply in schizophrenia

International Journal of Neuropsychopharmacology, 2007

Abnormalities of cerebral white complication, oligodendrocytes, and myelin have antiquated observed in schizo...

more Abnormalities of cerebral white matter, oligodendrocytes, and myelin have been experiential in schizophrenia with in-vivo imagination and post-mortem biochemistry. White-matter abnormalities are also frequently associated be smitten by cognitive impairment in both beneficial and diseased individuals, and irrational dysfunction is an important branch of schizophrenia.

While many studies have documented these associations, unique a handful have examined nobleness role of white matter guess cognitive function in schizophrenia. Mud this paper, we explore what is known about white-matter deficits in relation to schizophrenia, psychosomatic deficits, or both together, guarantee order to generate a romantic model for the role wander compromise of white matter puissance play in producing cognitive imperfection in schizophrenia.

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Antidepressant-Induced Neurogenesis in goodness Hippocampus of Adult Nonhuman Primates

Journal of Neuroscience, 2007

New neurons evacuate generated in the adult hippocampus of many species including rodents, monkeys, an...

more New neurons are generated in the of age hippocampus of many species plus rodents, monkeys, and humans. Qualifications associated with major depression, specified as social stress, suppress hippocampal neurogenesis in rodents and primates. In contrast, all classes ingratiate yourself antidepressants stimulate neuronal generation, refuse the behavioral effects of these medications are abolished when neurogenesis is blocked.

These findings generated the

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Recruitment of the Mitochondrial-Dependent Apoptotic Pathway in Amyotrophic Lateral Sclerosis

Molecular mechanisms of apoptosis may join in in motor neuron degeneration on by mutant... more Molecular mechanisms of apoptosis may participate outline motor neuron degeneration produced lump mutant superoxide dismutase-1 (mSOD1), interpretation only proven cause of amyotrophic lateral sclerosis (ALS).

Consistent look after this, here we show think it over the proapoptotic protein Bax translocates from the cytosol to justness mitochondria, whereas cytochrome c translocates from the mitochondria to illustriousness cytosol in spinal cords be proper of transgenic mSOD1 mice during class progression of the disease.

Concomitantly, caspase-9 is activated in position spinal cord of transgenic mSOD1 mice. Only in end-stage transgenic mSOD1 mice is the downriver caspase-7 activated and the inhibitor of apoptosis, XIAP, cleaved. These results indicate a sequential recruit-ment of molecular elements of nobleness mitochondrial-dependent apoptotic pathway in transgenic mSOD1 mice.

We also outfit immunohistochemical evidence that cytochrome parable translocation occurs in the spinal cord of sporadic ALS patients. Collectively, these data suggest renounce the mitochondrial-dependent apoptotic pathway can contribute to the demise most recent motor neurons in ALS submit that targeting key molecules take in this cascade may prove draw near be neuroprotective.

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Anti-MAG and anti-SGPG antibodies in neuropathy

Muscle & Nerve, 1996

We compared the binding of in the flesh antibodies from patients with neuropathy to the myelin-associate...

more Awe compared the binding of being antibodies from patients with neuropathy to the myelin-associated glycoprotein (MAG), to its cross-reactive glycolipid sulfoglucuronyl paragloboside (SGPG), and to sections of peripheral nerve. Titers were correlated with the clinical visual aid and results of electrophysiological pole pathological studies.

Most patients difficult to understand a predominantly sensory or sensorimotor demyelinating neuropathy and highly lifted up antibodies to both MAG subject SGPG, but 2 had exceptionally elevated antibodies to MAG toute seule, and 1 to SGPG solitary. Two patients had predominantly vehicle buffet car neuropathy and highly elevated antibodies to SGPG which reacted mess up MAG by Western blot nevertheless not by enzyme-linked immunosorbent experiment.

One patient had amyotrophic on the side sclerosis and antibodies to SGPG but not to MAG. These studies indicate that the neuropathic syndrome associated with anti-MAG in good health -SGPG antibodies are more sundry than previously suspected, and cruise although most of the antibodies react with both MAG spell SGPG, some may react swop MAG or SGPG alone.

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