Effect of maternal hypothyroxinaemia in the rat on brain biochemistry in adult progeny

1990 ◽  
Vol 124 (3) ◽  
pp. 387-396 ◽  
Author(s):  
M. Hadjzadeh ◽  
A. K. Sinha ◽  
M. R. Pickard ◽  
R. P. Ekins
Keyword(s):  
Brain Regions ◽  
Marker Enzyme ◽  
Cell Marker ◽  
Neurological Damage ◽  
Thyroid Status ◽  
Myelin Lipid ◽  
Neuronal Marker ◽  
Irreversible Effects ◽  
Myelin Metabolism ◽  
Glial Marker

ABSTRACT The effects of maternal hypothyroxinaemia during pregnancy on subsequent brain biochemistry in progeny was studied. Normal and partially thyroidectomized rat dams were mated and progeny allowed to grow to adulthood. Brain regions (cerebellum, medulla, midbrain, cerebral cortex and paleocortex) were dissected out and the activities of various cell marker enzymes were determined, along with cholesterol contents. Maternal hypothyroxinaemia was without effect on body weight, brain weight or thyroid status of adult progeny. Oligodendroglial marker enzyme activities were altered in progeny from thyroidectomized dams. 2′,3′-Cyclic nucleotide 3′-phosphohydrolase was decreased in the medulla (by 37%) and midbrain (by 32%). 5′-Nucleotidase was also diminished in the same brain regions, by 33% in the medulla and by 35% in the midbrain. In contrast, oleate esterase was increased (by 39%) in the paleocortex. Although these enzymes are putatively involved in myelin metabolism, no changes were observed in the concentration of a major myelin lipid (cholesterol). The activity of β-d-glucuronidase (a general neuronal marker) was decreased (by 30%) in the paleocortex, whereas N-acetyl-β-d-galactosaminidase (a general glial marker) was unchanged in all brain regions. In summary, maternal hypothyroxinaemia has irreversible effects on brain biochemistry in adult progeny. The damage is parameter-selective and brain region-specific, analogous to the pattern of neurological damage seen in offspring born to hypothyroxinaemic women in iodine-deficient endemias. Journal of Endocrinology (1990) 124, 387–396

scholarly journals Mood Disorders Are Glial Disorders: Evidence from In Vivo Studies

2010 ◽  
Vol 2010 ◽  
pp. 1-7 ◽  
Author(s):  
Matthias L. Schroeter ◽  
Hashim Abdul-Khaliq ◽  
Julia Sacher ◽  
Johann Steiner ◽  
Ingolf E. Blasig ◽  
...  
Keyword(s):  
Mood Disorders ◽  
Neuron Specific Enolase ◽  
In Vivo Studies ◽  
Diagnostic Biomarker ◽  
Major Depressive ◽  
Neuronal Marker ◽  
Serum S100b ◽  
Antidepressive Treatment ◽  
Glial Marker

It has recently been suggested that mood disorders can be characterized by glial pathology as indicated by histopathological postmortem findings. Here, we review studies investigating the glial marker S100B in serum of patients with mood disorders. This protein might act as a growth and differentiation factor. It is located in, and may actively be released by, astro- and oligodendrocytes. Studies consistently show that S100B is elevated in mood disorders; more strongly in major depressive than bipolar disorder. Successful antidepressive treatment reduces S100B in major depression whereas there is no evidence of treatment effects in mania. In contrast to the glial marker S100B, the neuronal marker protein neuron-specific enolase is unaltered. By indicating glial alterations without neuronal changes, serum S100B studies confirm specific glial pathology in mood disorders in vivo. S100B can be regarded as a potential diagnostic biomarker for mood disorders and as a biomarker for successful antidepressive treatment.

scholarly journals Lidocaine is a nocebo treatment for trigeminally mediated magnetic orientation in birds

2018 ◽  
Vol 15 (145) ◽  
pp. 20180124 ◽  
Author(s):  
Svenja Engels ◽  
Christoph Daniel Treiber ◽  
Marion Claudia Salzer ◽  
Andreas Michalik ◽  
Lyubov Ushakova ◽  
...  
Keyword(s):  
Magnetic Field ◽  
Prussian Blue ◽  
Trigeminal Nerve ◽  
Brain Regions ◽  
Blue Staining ◽  
Magnetic Orientation ◽  
Neuronal Activation ◽  
Neuronal Marker ◽  
Prussian Blue Staining ◽  
Ophthalmic Branch

Even though previously described iron-containing structures in the upper beak of pigeons were almost certainly macrophages, not magnetosensitive neurons, behavioural and neurobiological evidence still supports the involvement of the ophthalmic branch of the trigeminal nerve (V1) in magnetoreception. In previous behavioural studies, inactivation of putative V1-associated magnetoreceptors involved either application of the surface anaesthetic lidocaine to the upper beak or sectioning of V1. Here, we compared the effects of lidocaine treatment, V1 ablations and sham ablations on magnetic field-driven neuronal activation in V1-recipient brain regions in European robins. V1 sectioning led to significantly fewer Egr-1-expressing neurons in the trigeminal brainstem than in the sham-ablated birds, whereas lidocaine treatment had no effect on neuronal activation. Furthermore, Prussian blue staining showed that nearly all iron-containing cells in the subepidermal layer of the upper beak are nucleated and are thus not part of the trigeminal nerve, and iron-containing cells appeared in highly variable numbers at inconsistent locations between individual robins and showed no systematic colocalization with a neuronal marker. Our data suggest that lidocaine treatment has been a nocebo to the birds and a placebo for the experimenters. Currently, the nature and location of any V1-associated magnetosensor remains elusive.

scholarly journals Thyroid hormones promote cell differentiation and up-regulate the expression of the seladin-1 gene in in vitro models of human neuronal precursors

2008 ◽  
Vol 197 (2) ◽  
pp. 437-446 ◽  
Author(s):  
S Benvenuti ◽  
P Luciani ◽  
I Cellai ◽  
C Deledda ◽  
S Baglioni ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Differentiation ◽  
Thyroid Hormones ◽  
Brain Regions ◽  
Developing Brain ◽  
Neuronal Marker ◽  
Neuronal Precursor Cells ◽  
Neuronal Precursors

Thyroid hormones (TH) play an important role in the development of human brain, by regulating the expression of specific genes. Selective Alzheimer's disease indicator-1 (seladin-1) is a recently discovered gene with neuroprotective properties, which has been found to be down-regulated in brain regions affected by Alzheimer's disease. Seladin-1 has anti-apoptotic properties mainly due to the inhibition of the activation of caspase 3. The aim of this study was to determine whether seladin-1 may be regarded as a new mediator of the effects of TH in the developing brain. In order to demonstrate this hypothesis, the effects of TH both on cell differentiation and on the expression of seladin-1 were assessed in two different cell models, i.e. fetal human neuroepithelial cells (FNC) and human mesenchymal stem cells (hMSC), which can be differentiated into neurons. 3,3′,5-Triiodothyronine (T3) determined different biological responses (inhibition of cell adhesion, induction of migration, and increase in the expression of the neuronal marker neurofilament-M and Na+ and Ca2+ channel functionality) in both FNC and hMSC, which express TH receptors. Then, we showed that TH significantly increase the expression levels of seladin-1, and that T3 effectively prevents camptothecin-induced apoptosis. However, in hMSC-derived neurons the expression of seladin-1 was not affected by TH. Our results demonstrated for the first time that seladin-1 is a novel TH-regulated gene in neuronal precursors. In view of its anti-apoptotic activity, it might be hypothesized that one of the functions of the increased seladin-1 levels in the developing brain may be to protect neuronal precursor cells from death.

scholarly journals Numerical Study on Electrode Design for Rodent Deep Brain Stimulation With Implantations Cranial to Targeted Nuclei

2021 ◽  
Vol 15 ◽  
Author(s):  
Konstantin Butenko ◽  
Rüdiger Köhling ◽  
Ursula van Rienen
Keyword(s):  
Deep Brain Stimulation ◽  
Electric Fields ◽  
Brain Stimulation ◽  
Numerical Study ◽  
Brain Regions ◽  
Electrode Design ◽  
Rodent Models ◽  
Neurological Damage ◽  
Direct Targeting ◽  
Deep Brain

The globus pallidus internus and the subthalamic nucleus are common targets for deep brain stimulation to alleviate symptoms of Parkinson's disease and dystonia. In the rodent models, however, their direct targeting is hindered by the relatively large dimensions of applied electrodes. To reduce the neurological damage, the electrodes are usually implanted cranial to the nuclei, thus exposing the non-targeted brain regions to large electric fields and, in turn, possible undesired stimulation effects. In this numerical study, we analyze the spread of the fields for the conventional electrodes and several modifications. As a result, we present a relatively simple electrode design that allows an efficient focalization of the stimulating field in the inferiorly located nuclei.

scholarly journals Autophagy in Spinocerebellar ataxia type 2, a dysregulated pathway, and a target for therapy

2021 ◽  
Vol 12 (12) ◽  
Author(s):  
Adriana Marcelo ◽  
Inês T. Afonso ◽  
Ricardo Afonso-Reis ◽  
David V. C. Brito ◽  
Rafael G. Costa ◽  
...  
Keyword(s):  
Spinocerebellar Ataxia ◽  
Neurodegenerative Disorder ◽  
Clinical Manifestations ◽  
Brain Regions ◽  
Spinocerebellar Ataxia Type ◽  
Spinocerebellar Ataxia Type 2 ◽  
Neuronal Marker ◽  
Severe Motor ◽  
Ataxin 2

AbstractSpinocerebellar ataxia type 2 (SCA2) is an incurable and genetic neurodegenerative disorder. The disease is characterized by progressive degeneration of several brain regions, resulting in severe motor and non-motor clinical manifestations. The mutation causing SCA2 disease is an abnormal expansion of CAG trinucleotide repeats in the ATXN2 gene, leading to a toxic expanded polyglutamine segment in the translated ataxin-2 protein. While the genetic cause is well established, the exact mechanisms behind neuronal death induced by mutant ataxin-2 are not yet completely understood. Thus, the goal of this study is to investigate the role of autophagy in SCA2 pathogenesis and investigate its suitability as a target for therapeutic intervention. For that, we developed and characterized a new striatal lentiviral mouse model that resembled several neuropathological hallmarks observed in SCA2 disease, including formation of aggregates, neuronal marker loss, cell death and neuroinflammation. In this new model, we analyzed autophagic markers, which were also analyzed in a SCA2 cellular model and in human post-mortem brain samples. Our results showed altered levels of SQSTM1 and LC3B in cells and tissues expressing mutant ataxin-2. Moreover, an abnormal accumulation of these markers was detected in SCA2 patients’ striatum and cerebellum. Importantly, the molecular activation of autophagy, using the compound cordycepin, mitigated the phenotypic alterations observed in disease models. Overall, our study suggests an important role for autophagy in the context of SCA2 pathology, proposing that targeting this pathway could be a potential target to treat SCA2 patients.

Abstract 163: Delayed Administration of Perlecan Doman V Significantly Increases Neurogenesis and Improves Functional Outcome after Experimental Ischemic Stroke

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Aileen Marcelo-McCabe ◽  
Leon de Hoog ◽  
Andrew Clarkson ◽  
Michael Kahle ◽  
Gregory Bix
Keyword(s):  
Ischemic Stroke ◽  
Functional Outcome ◽  
Brain Regions ◽  
Functional Improvement ◽  
Experimental Stroke ◽  
Neuronal Marker ◽  
Delayed Treatment ◽  
Post Stroke ◽  
Mca Occlusion ◽  
Domain V

Stroke, a major cause of significant morbidity and death, has limited therapeutic options. To that end, our goal is to develop novel stroke therapies by exploiting the brain’s own neuroreparative potential. We have discovered that perlecan, a prominent brain extracellular matrix proteoglycan, is proteolyzed into the bioactive protein fragment domain V (DV) after experimental and human ischemic stroke. DV is both neuroprotective and pro-angiogenic. Furthermore, functional outcome can be significantly improved in rodents by administering DV 6-24 hours after experimental transient (distal MCA occlusion) or permanent (photothrombosis) stroke. Here we studied in mechanistic detail whether delayed DV administration (initiated 7 days post-stroke) could increase neurogenesis and improve functional outcome after mouse transient MCA occlusion. Delayed DV administration also served to minimize confounding neuroprotective and angiogenic effects which occur with acute DV therapy. After two doses of DV (post-stroke day 7 and 9), stroked 3-month old male C57BL6 mice had significant functional improvement (rotor rod) compared to vehicle treated stroke controls. Brain immunohistochemistry 21 days after stroke demonstrated that DV treated mice had significantly more cells that were positive for BrdU (a marker of cell division), doublecortin (DCX, a marker for immature neurons), and NeuN (another neuronal marker) in the infarct area. Furthermore, stereotactic brain injection (AP + 0.00, ML - 1.2, DV – 2.5) with alpha 2 integrin (a known neuronal DV receptor) function blocking antibody on post-stroke day 3 inhibited DV’s post-stroke neurogenic effects. These results suggest that delayed DV treatment after experimental stroke increases neurogenesis, increases the number of new neurons that reach stroked brain regions and survive there, and improves functional outcome through an alpha 2 integrin dependent mechanism. Importantly, as we are unaware of any other delayed treatment other than FLAME clinical trial (fluoxetine treatment initiated 5-10 days after stroke) that significantly improves functional outcome after stroke, our data further suggest the promise of DV as an effective stroke therapy.

The neuronal pathology of schizophrenia: molecules and mechanisms

2007 ◽  
Vol 35 (2) ◽  
pp. 433-436 ◽  
Author(s):  
G.P. Reynolds ◽  
M.K. Harte
Keyword(s):  
Animal Models ◽  
Glutamate Transporter ◽  
Neuronal Loss ◽  
Brain Regions ◽  
Vesicular Glutamate Transporter ◽  
Neuronal Marker ◽  
Functional Relevance ◽  
Glutamate Transporter 1 ◽  
The Brain ◽  
Neuronal Pathology

There is an accumulation of evidence for abnormalities in schizophrenia of both the major neurotransmitter systems of the brain – those of GABA (γ-aminobutyric acid) and glutamate. Initial studies have found deficits in the putative neuronal marker, N-acetylaspartate, in a number of brain regions in schizophrenia. The animal models have provided some interesting correlates and discrepancies with these findings. The deficit in inhibitory interneurons within structures implicated in schizophrenic symptomatology may well have direct functional relevance, and can be induced by animal models of the disease such as subchronic phencyclidine administration or social isolation. Their association with these animal models suggests an environmental involvement. A loss of glutamatergic function in schizophrenia is supported by decreases in markers for the neuronal glutamate transporter in striatal structures that receive cortical glutamatergic projections. Deficits in the VGluT1 (vesicular glutamate transporter-1) in both striatal and hippocampal regions support this observation, and the association of VGluT1 density with a genetic risk factor for schizophrenia points to genetic influences on these glutamatergic deficits. Further studies differentiating neuronal loss from diminished activity and improved models allowing us to determine the temporal and causal relationships between GABAergic and glutamatergic deficits will lead to a better understanding of the processes underlying the neuronal pathology of schizophrenia.

Synaptic organization of the gustatory NST

1994 ◽  
Vol 52 ◽  
pp. 150-151
Author(s):  
M. C. Whitehead
Keyword(s):  
Central Nervous System ◽  
Dendritic Spines ◽  
Fundamental Problem ◽  
Cell Types ◽  
Brain Regions ◽  
Excitatory Synapses ◽  
Solitary Tract ◽  
Synaptic Organization ◽  
Synaptic Junctions ◽  
Afferent Terminals

A fundamental problem in taste research is to determine how gustatory signals are processed and disseminated in the mammalian central nervous system. An important first step toward understanding information processing is the identification of cell types in the nucleus of the solitary tract (NST) and their synaptic relationships with oral primary afferent terminals. Facial and glossopharyngeal (LIX) terminals in the hamster were labelled with HRP, examined with EM, and characterized as containing moderate concentrations of medium-sized round vesicles, and engaging in asymmetrical synaptic junctions. Ultrastructurally the endings resemble excitatory synapses in other brain regions.Labelled facial afferent endings in the RC subdivision synapse almost exclusively with distal dendrites and dendritic spines of NST cells. Most synaptic relationships between the facial synapses and the dendrites are simple. However, 40% of facial endings engage in complex synaptic relationships within glomeruli containing unlabelled axon endings particularly ones termed "SP" endings. SP endings are densely packed with small, pleomorphic vesicles and synapse with both the facial endings and their postsynaptic dendrites by means of nearly symmetrical junctions.

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