Neurochemical differences in two rat strains exposed to social isolation rearing

2012 ◽  
Vol 24 (5) ◽  
pp. 286-295 ◽  
Author(s):  
Luigia Trabace ◽  
Margherita Zotti ◽  
Marilena Colaianna ◽  
Maria G. Morgese ◽  
Stefania Schiavone ◽  
...  
Keyword(s):  
High Performance ◽  
Tissue Concentration ◽  
Brain Area ◽  
Brain Regions ◽  
Post Mortem ◽  
Isolation Rearing ◽  
Post Mortem Brain ◽  
Rat Strain ◽  
Neurochemical Changes

Objective: Isolation rearing of rats provides a non-pharmacological method of inducing behavioural changes in rodents that resemble schizophrenia or depression. Nevertheless, results are variable within different strains. We focused on neurochemical changes in several in vivo and post-mortem brain regions of Wistar (W) and Lister Hooded (LH) rats following post-weaning social separation.Methods: Experiments were conducted after 6–8 weeks of isolation. For post-mortem studies, prefrontal cortex (PFC), nucleus accumbens (NAC), hippocampus (Hipp) and striatum (St) were collected by tissue dissection. In vivo experiments were conducted by microdialysis in the PFC. Analyses of dopamine (DA), serotonin (5-HT) levels and relative turnover were performed by using high-performance liquid chromatography.Results: We found significant strain-related differences in biogenic amine content. LH rats were characterised by markedly raised DA, along with its turnover reduction, in all the post-mortem brain regions examined as well as in microdialysis samples, while in W rats 5-HT tissue concentration was lower in PFC and St and higher in NAC and Hipp. Cortical extracellular 5-HT concentrations were increased in group housed and decreased in isolated W animals. Moreover, isolation increased DA concentrations in the PFC of LH rats, and decreased 5-HT in W rats in NAC and Hipp. Lately, 5-HT turnover was also affected by both strain and isolation conditions.Conclusions: This study suggests that W and LH rats have markedly different neurochemical profiles in response to isolation, resulting in altered monoamine levels that vary according to brain area and rat strain. These findings highlight the importance of selecting an appropriate rat strain when considering isolation rearing to model symptoms of schizophrenia and/or depression.

scholarly journals Platelet phosphorylated TDP-43: An exploratory study for a peripheral surrogate biomarker development for Alzheimer’s disease

2017 ◽  
Author(s):  
Rodger Wilhite ◽  
Jessica Sage ◽  
Abdurrahman Bouzid ◽  
Tyler Primavera ◽  
Abdulbaki Agbas
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Stage ◽  
Clinical Signs ◽  
Brain Regions ◽  
Post Mortem ◽  
Disease Prognosis ◽  
Post Mortem Brain ◽  
And Control ◽  
Lateral Sclerosis

AbstractAim: Alzheimer’s disease (AD) and other forms of dementia create a non-curable disease population in World’s societies. To develop a blood-based biomarker is important so that the remedial or disease-altering therapeutic intervention for AD patients would be available at the early stage. Materials & Methods: TDP-43 levels were analyzed in post-mortem brain tissue and platelets of AD and control subjects. Results: We observed an increased TDP-43 (<60%) in post-mortem AD brain regions and similar trends were also observed in patient’s platelets. Conclusion: Platelet TDP-43 could be used as a surrogate biomarker that is measurable, reproducible, and sensitive for screening the patients with some early clinical signs of AD and can be used to monitor disease prognosis.Lay abstractIn this study, we explore to identify an Alzheimer’s disease-selective phospho-specific antibody that recognizes the diseased form of TDP-43 protein in patient’s blood-derived platelets. Our results suggest that selective anti-phosphorylated TDP-43 antibody discriminates Alzheimer’s disease from non-demented controls and patients with amyotrophic lateral sclerosis. Therefore, platelet screening with a selective antibody could potentially be a useful tool for diagnostic purposes for Alzheimer’s disease.

Induction of Parkinsonian-Like Changes via Targeted Downregulation of Astrocytic Glutamate Transporter GLT-1 in the Striatum

2021 ◽  
pp. 1-20
Author(s):  
Chao Ren ◽  
Kai-Jie He ◽  
Hua Hu ◽  
Jin-Bao Zhang ◽  
Li-Guo Dong ◽  
...  
Keyword(s):  
Western Blotting ◽  
High Performance ◽  
Brain Area ◽  
Glutamate Transporter ◽  
Glutamate Excitotoxicity ◽  
Calcium Signal ◽  
Abnormal Gait ◽  
Pet Ct

Background: Previous investigations have suggested that decreased expression of glutamate transporter-1 (GLT-1) is involved in glutamate excitotoxicity and contribute to the development of Parkinson’s disease (PD), GLT-1 is decreased in animal models of PD. GLT-1 is mainly expressed in astrocytes, and the striatum is a GLT-1-rich brain area. Objective: The aim was to explore the function and mechanism of astrocytic GLT-1 in PD-like changes. Methods: In the study, PD-like changes and their molecular mechanism in rodents were tested by a behavioral assessment, micro-positron emission tomography/computed tomography (PET/CT), western blotting, immunohistochemical and immunofluorescence staining, and high performance liquid chromatography pre-column derivatization with O-pthaldialdehida after downregulating astrocytic GLT-1 in vivo and in vitro. Results: In vivo, after 6 weeks of brain stereotactic injection of adeno-associated virus into the striatum, rats in the astrocytic GLT-1 knockdown group showed poorer motor performance, abnormal gait, and depression-like feature; but no olfactory disorders. The results of micro-PET/CT and western blotting indicated that the dopaminergic system was impaired in astrocytic GLT-1 knockdown rats. Similarly, tyrosine hydroxylase (TH) positive immune-staining in neurons of astrocytic GLT-1 knockdown rats showed deficit in cell count. In vitro, knockdown of astrocytic GLT-1 via RNA interference led to morphological injury of TH-positive neurons, which may be related to the abnormal calcium signal induced by glutamate accumulation after GLT-1 knockdown. Furthermore, the GLT-1 agonist ceftriaxone showed a protective effect on TH-positive neuron impairment. Conclusion: The present findings may shed new light on the future prevention and treatment of PD based on blocking glutamate excitotoxicity.

Magnetic Resonance Spectroscopy and its Applications in Psychiatry

2002 ◽  
Vol 36 (1) ◽  
pp. 31-43 ◽  
Author(s):  
Gin S. Malhi ◽  
Michael Valenzuela ◽  
Wei Wen ◽  
Perminder Sachdev
Keyword(s):  
Magnetic Resonance ◽  
Magnetic Resonance Spectroscopy ◽  
Brain Regions ◽  
Response To Treatment ◽  
Resonance Spectroscopy ◽  
Biochemical Basis ◽  
Non Invasive ◽  
Investigative Technique ◽  
Neurochemical Changes

Objective: This paper briefly describes neuroimaging using magnetic resonance spectroscopy (MRS) and provides a systematic review of its application to psychiatric disorders. Method: A literature review ( Index Medicus/ Medline) was carried out, as well as a review of other relevant papers and data known to the authors. Results: Magnetic resonance spectroscopy is a complex and sophisticated neuroimaging technique that allows reliable and reproducible quantification of brain neurochemistry provided its limitations are respected. In some branches of medicine it is already used clinically, for instance, to diagnose tumours and in psychiatry its applications are gradually extending beyond research. Neurochemical changes have been found in a variety of brain regions in dementia, schizophrenia and affective disorders and promising discoveries have also been made in anxiety disorders. Conclusions: Magnetic resonance spectroscopy is a non-invasive investigative technique that has provided useful insights into the biochemical basis of many neuropsychiatric disorders. It allows direct measurement, in vivo, of medication levels within the brain and has made it possible to track the neurochemical changes that occur as a consequence of disease and ageing or in response to treatment. It is an extremely useful advance in neuroimaging technology and one that will undoubtedly have many clinical uses in the near future.

scholarly journals The transcriptional landscape of cortical interneurons underlies in-vivo brain function and schizophrenia risk

2018 ◽  
Author(s):  
Kevin M Anderson ◽  
Meghan A Collins ◽  
Rowena Chin ◽  
Tian Ge ◽  
Monica D Rosenberg ◽  
...  
Keyword(s):  
General Population ◽  
Brain Tissue ◽  
Functional Mri ◽  
Resting State ◽  
Brain Function ◽  
Signal Amplitude ◽  
Spatial Distributions ◽  
Post Mortem ◽  
Post Mortem Brain

AbstractInhibitory interneurons orchestrate information flow across cortex and are implicated in psychiatric illness. Although classes of interneurons have unique functional properties and spatial distributions throughout the brain, the relative influence of interneuron subtypes on brain function, cortical specialization, and illness risk remains elusive. Here, we demonstrate stereotyped organizational properties of somatostatin and parvalbumin related transcripts within human and non-human primates. Interneuron spatial distributions recapitulate cortico-striato-thalamic functional networks and track regional differences in functional MRI signal amplitude. In the general population (n=9,627), parvalbumin-linked genes account for an enriched proportion of genome-wide heritable variance in in-vivo functional MRI signal amplitude. This relationship is spatially dependent, following the topographic organization of parvalbumin expression in independent post-mortem brain tissue. Finally, genetic risk for schizophrenia is enriched among interneuron-linked genes and predictive of cortical signal amplitude in parvalbumin-biased regions. These data indicate that the molecular genetic basis of resting-state brain function across cortex is shaped by the spatial distribution of interneuron-related transcripts and underlies individual differences in risk for schizophrenia.Key FindingsSpatial distributions of somatostatin (SST) and parvalbumin (PVALB) are negatively correlated in mature human and non-human primate cortex, paralleling patterns observed in utero.SST and PVALB are differentially expressed within distinct limbic and somato/motor cortico-striato-thalamic networks, respectively.In-vivo resting-state signal amplitude is heritable in the general population and tracks relative SST/PVALB expression across cortex.Single-nucleotide polymorphisms tied to PVALB-related genes account for an enriched proportion of the heritable variance in resting-state signal amplitude.PVALB-mediated heritability of resting-state signal amplitude in the general population is spatially heterogeneous, mirroring the cortical expression of PVALB in independent post-mortem brain tissue.Polygenic risk for schizophrenia is enriched among interneuron-linked genes and predicts resting-state signal amplitude in a manner that also follows the cortical expression of PVALB.

scholarly journals Widespread Decrease of Cerebral Vimentin-Immunoreactive Astrocytes in Depressed Suicides

2021 ◽  
Vol 12 ◽  
Author(s):  
Liam Anuj O'Leary ◽  
Claudia Belliveau ◽  
Maria Antonietta Davoli ◽  
Jie Christopher Ma ◽  
Arnaud Tanti ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Blood Vessels ◽  
Close Association ◽  
Brain Regions ◽  
Quantitative Comparison ◽  
Post Mortem ◽  
Dorsomedial Prefrontal Cortex ◽  
Post Mortem Brain ◽  
Morphometric Features ◽  
Fine Morphology

Post-mortem investigations have implicated cerebral astrocytes immunoreactive (-IR) for glial fibrillary acidic protein (GFAP) in the etiopathology of depression and suicide. However, it remains unclear whether astrocytic subpopulations IR for other astrocytic markers are similarly affected. Astrocytes IR to vimentin (VIM) display different regional densities than GFAP-IR astrocytes in the healthy brain, and so may be differently altered in depression and suicide. To investigate this, we compared the densities of GFAP-IR astrocytes and VIM-IR astrocytes in post-mortem brain samples from depressed suicides and matched non-psychiatric controls in three brain regions (dorsomedial prefrontal cortex, dorsal caudate nucleus and mediodorsal thalamus). A quantitative comparison of the fine morphology of VIM-IR astrocytes was also performed in the same regions and subjects. Finally, given the close association between astrocytes and blood vessels, we also assessed densities of CD31-IR blood vessels. Like for GFAP-IR astrocytes, VIM-IR astrocyte densities were found to be globally reduced in depressed suicides relative to controls. By contrast, CD31-IR blood vessel density and VIM-IR astrocyte morphometric features in these regions were similar between groups, except in prefrontal white matter, in which vascularization was increased and astrocytes displayed fewer primary processes. By revealing a widespread reduction of cerebral VIM-IR astrocytes in cases vs. controls, these findings further implicate astrocytic dysfunctions in depression and suicide.

scholarly journals Single-cell deconvolution of 3,000 post-mortem brain samples for eQTL and GWAS dissection in mental disorders

2021 ◽  
Author(s):  
Yongjin Park ◽  
Liang He ◽  
Jose Davila-Velderrain ◽  
Lei Hou ◽  
Shahin Mohammadi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Single Cell ◽  
Genetic Variants ◽  
Cell Types ◽  
Brain Regions ◽  
Post Mortem ◽  
Rna Seq ◽  
Cell Type ◽  
Post Mortem Brain ◽  
Cell Type Specific

AbstractThousands of genetic variants acting in multiple cell types underlie complex disorders, yet most gene expression studies profile only bulk tissues, making it hard to resolve where genetic and non-genetic contributors act. This is particularly important for psychiatric and neurodegenerative disorders that impact multiple brain cell types with highly-distinct gene expression patterns and proportions. To address this challenge, we develop a new framework, SPLITR, that integrates single-nucleus and bulk RNA-seq data, enabling phenotype-aware deconvolution and correcting for systematic discrepancies between bulk and single-cell data. We deconvolved 3,387 post-mortem brain samples across 1,127 individuals and in multiple brain regions. We find that cell proportion varies across brain regions, individuals, disease status, and genotype, including genetic variants in TMEM106B that impact inhibitory neuron fraction and 4,757 cell-type-specific eQTLs. Our results demonstrate the power of jointly analyzing bulk and single-cell RNA-seq to provide insights into cell-type-specific mechanisms for complex brain disorders.

Hyperlocomotion during Recovery from Isoflurane Anesthesia Is Associated with Increased Dopamine Turnover in the Nucleus Accumbens and Striatum in Mice

1997 ◽  
Vol 86 (2) ◽  
pp. 464-475 ◽  
Author(s):  
Masahiro Irifune ◽  
Tomoaki Sato ◽  
Takashige Nishikawa ◽  
Takashi Masuyama ◽  
Masahiro Nomoto ◽  
...  
Keyword(s):  
Locomotor Activity ◽  
Nucleus Accumbens ◽  
High Performance ◽  
Gas Flow ◽  
Brain Regions ◽  
Dopamine Neurons ◽  
Dopamine Turnover

Background It was recently reported that isoflurane increases dopamine release in the striatum in rats both in vivo and in vitro, and that isoflurane inhibits uptake of dopamine in the rat brain synaptosomes. However, the functional role of these effects of isoflurane on dopamine neurons is uncertain. Dopaminergic mechanisms within the nucleus accumbens and striatum play an important role in the control of locomotor activity, and a change in dopamine turnover depends essentially on a change in impulse flow in the dopamine neurons. In this study, the effects of isoflurane on locomotor activity and on dopamine turnover were investigated in discrete brain regions in mice. Methods Mice were placed in individual airtight clear plastic chambers and spontaneously breathed isoflurane in 25% oxygen and 75% nitrogen (fresh gas flow, 4 l/min). Locomotor activity was measured with an Animex activity meter. Animals were decapitated after treatments with or without isoflurane, and the concentrations of monoamines and their metabolites in different brain areas were measured by high-performance liquid chromatography. Results During the 10 min after the cessation of the 20-min exposure to isoflurane, there was a significant increase in locomotor activity in animals breathing 1.5% isoflurane but not 0.7% isoflurane. This increase in locomotor activity produced by 1.5% isoflurane was abolished by a low dose of haloperidol (0.1 mg/kg), a dopamine receptor antagonist. Regional brain monoamine assays revealed that 1.5% isoflurane significantly increased the 3,4-dihydroxyphenylacetic acid:dopamine ratio (one indicator of transmitter turnover) in the nucleus accumbens and striatum, but a concentration of 0.7% did not. This significant increase in dopamine turnover in these regions continued during 20 min after the cessation of the administration of 1.5% isoflurane. Conclusions These results suggest that isoflurane-induced hyperlocomotion during emergence may be associated with increased dopamine turnover in the nucleus accumbens and striatum.

scholarly journals Angle-Tuned Coils: Enabling Building Blocks for High Performance and Multisite TMS Systems

2021 ◽  
Author(s):  
Hedyeh Bagherzadeh ◽  
QINGLEI MENG ◽  
Zhi-De Deng ◽  
Hanbing Lu ◽  
Elliott Hong ◽  
...  
Keyword(s):  
Electric Field ◽  
Composite Structures ◽  
High Performance ◽  
Near Field ◽  
Building Blocks ◽  
Brain Regions ◽  
Brain Functions ◽  
Surface Areas ◽  
Head Surface

Objective: A novel angle-tuned ring coil is proposed for improving the depth-spread performance of Transcranial Magnetic Stimulation (TMS) coils and serve as the building blocks for high-performance composite coils and multisite TMS systems. Approach: Improving depth-spread performance by reducing field divergence through creating a more elliptical emitted field distribution from the coil. To accomplish that, instead of enriching the Fourier components along the planarized (x-y) directions, which requires different arrays to occupy large brain surface areas, we worked along the radial (z) direction by using tilted coil angles and stacking coil numbers to reduce the divergence of the emitted near field without occupying large head surface areas. The emitted electric field distributions were theoretically simulated in spherical and real human head models to analyze the depth-spread performance of proposed coils and compare with existing figure-8 coils. The results were then experimentally validated with field probes and in-vivo animal tests. Main Results: The proposed "angle-tuning" concept improves the depth-spread performance of individual coils with a significantly smaller footprint than existing and proposed coils. For composite structures, using the proposed coils as basic building blocks simplifies the design and manufacturing process and helps accomplish a leading depth-spread performance. In addition, the footprint of the proposed system is intrinsically small, making them suitable for multisite stimulations of inter and intra-hemispheric brain regions with an improved spread and less electric field divergence. Significance: Few brain functions are operated by isolated single brain regions but rather by coordinated networks involving multiple brain regions. Simultaneous or sequential multisite stimulations may provide tools for mechanistic studies of brain functions and the treatment of neuropsychiatric disorders. The proposed AT coil goes beyond the traditional depth-spread tradeoff rule of TMS coils, which provides the possibility of building new composite structures and new multisite TMS tools.

scholarly journals Post mortem brain temperature and its influence on quantitative MRI of the brain

2021 ◽  
Author(s):  
Celine Berger ◽  
Melanie Bauer ◽  
Holger Wittig ◽  
Eva Scheurer ◽  
Claudia Lenz
Keyword(s):  
Linear Models ◽  
Brain Temperature ◽  
Brain Mri ◽  
Mean Diffusivity ◽  
Quantitative Mri ◽  
Positive Temperature ◽  
Post Mortem ◽  
Post Mortem Brain

Abstract Objective MRI temperature sensitivity presents a major issue in in situ post mortem MRI (PMMRI), as the tissue temperatures differ from living persons due to passive cooling of the deceased. This study aims at computing brain temperature effects on the MRI parameters to correct for temperature in PMMRI, laying the foundation for future projects on post mortem validation of in vivo MRI techniques. Materials and methods Brain MRI parameters were assessed in vivo and in situ post mortem using a 3 T MRI scanner. Post mortem brain temperature was measured in situ transethmoidally. The temperature effect was computed by fitting a linear model to the MRI parameters and the corresponding brain temperature. Results Linear positive temperature correlations were observed for T1, T2* and mean diffusivity in all tissue types. A significant negative correlation was observed for T2 in white matter. Fractional anisotropy revealed significant correlations in all gray matter regions except for the thalamus. Discussion The linear models will allow to correct for temperature in post mortem MRI. Comparing in vivo to post mortem conditions, the mean diffusivity, in contrast to T1 and T2, revealed additional effects besides temperature, such as cessation of perfusion and active diffusion.

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