scholarly journals Early postnatal irradiation‐induced age‐dependent changes in adult mouse brain: MRI based characterization

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Bo Xu Ren ◽  
Isaac Huen ◽  
Zi Jun Wu ◽  
Hong Wang ◽  
Meng Yun Duan ◽  
...  
Keyword(s):  
Cell Division ◽  
Radiation Exposure ◽  
Developmental Stages ◽  
Granule Cells ◽  
Brain Mri ◽  
Brain Regions ◽  
Hippocampal Neurogenesis ◽  
Cerebellar Hemisphere ◽  
Parietal Region ◽  
Olfactory Bulbs

Abstract Background Brain radiation exposure, in particular, radiotherapy, can induce cognitive impairment in patients, with significant effects persisting for the rest of their life. However, the main mechanisms leading to this adverse event remain largely unknown. A study of radiation-induced injury to multiple brain regions, focused on the hippocampus, may shed light on neuroanatomic bases of neurocognitive impairments in patients. Hence, we irradiated BALB/c mice (male and female) at postnatal day 3 (P3), day 10 (P10), and day 21 (P21) and investigated the long-term radiation effect on brain MRI changes and hippocampal neurogenesis. Results We found characteristic brain volume reductions in the hippocampus, olfactory bulbs, the cerebellar hemisphere, cerebellar white matter (WM) and cerebellar vermis WM, cingulate, occipital and frontal cortices, cerebellar flocculonodular WM, parietal region, endopiriform claustrum, and entorhinal cortex after irradiation with 5 Gy at P3. Irradiation at P10 induced significant volume reduction in the cerebellum, parietal region, cingulate region, and olfactory bulbs, whereas the reduction of the volume in the entorhinal, parietal, insular, and frontal cortices was demonstrated after irradiation at P21. Immunohistochemical study with cell division marker Ki67 and immature marker doublecortin (DCX) indicated the reduced cell division and genesis of new neurons in the subgranular zone of the dentate gyrus in the hippocampus after irradiation at all three postnatal days, but the reduction of total granule cells in the stratum granulosun was found after irradiation at P3 and P10. Conclusions The early life radiation exposure during different developmental stages induces varied brain pathophysiological changes which may be related to the development of neurological and neuropsychological disorders later in life.

scholarly journals Coexistence of neuronal intranuclear inclusion disease and amyotrophic lateral sclerosis: an autopsy case

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Atsuhiko Sugiyama ◽  
Takahiro Takeda ◽  
Mizuho Koide ◽  
Hajime Yokota ◽  
Hiroki Mukai ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Neurons ◽  
Brain Mri ◽  
Brain Magnetic Resonance Imaging ◽  
Repeat Expansion ◽  
Cerebellar Hemisphere ◽  
Intranuclear Inclusions ◽  
Intranuclear Inclusion ◽  
Neuronal Intranuclear Inclusion ◽  
Lateral Sclerosis

Abstract Background Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disease. Pathologically, it is characterized by eosinophilic hyaline intranuclear inclusions in the cells of the visceral organs as well as central, peripheral, and autonomic nervous system cells. Recently, a GGC repeat expansion in the NOTCH2NLC gene has been identified as the etiopathological agent of NIID. Interestingly, this GGC repeat expansion was also reported in some patients with a clinical diagnosis of amyotrophic lateral sclerosis (ALS). However, there are no autopsy-confirmed cases of concurrent NIID and ALS. Case presentation A 60-year-old Taiwanese woman reported a four-month history of progressive weakness beginning in the right foot that spread to all four extremities. She was diagnosed with ALS because she met the revised El Escorial diagnostic criteria for definite ALS with upper and lower motor neuron involvement in the cervical, thoracic, and lumbosacral regions. She died of respiratory failure at 22 months from ALS onset, at the age of 62 years. Brain magnetic resonance imaging (MRI) revealed lesions in the medial part of the cerebellar hemisphere, right beside the vermis (paravermal lesions). The subclinical neuropathy, indicated by a nerve conduction study (NCS), prompted a potential diagnosis of NIID. Antemortem skin biopsy and autopsy confirmed the coexistence of pathology consistent with both ALS and NIID. We observed neither eccentric distribution of p62-positive intranuclear inclusions in the areas with abundant large motor neurons nor cytopathological coexistence of ALS and NIID pathology in motor neurons. This finding suggested that ALS and NIID developed independently in this patient. Conclusions We describe a case of concurrent NIID and ALS discovered during an autopsy. Abnormal brain MRI findings, including paravermal lesions, could indicate the coexistence of NIID even in patients with ALS showing characteristic clinical phenotypes.

Craniofacial, vestibular and bone defects in mice lacking the Distal-less-related gene Dlx5

Development ◽  
1999 ◽  
Vol 126 (17) ◽  
pp. 3795-3809 ◽  
Author(s):  
D. Acampora ◽  
G.R. Merlo ◽  
L. Paleari ◽  
B. Zerega ◽  
M.P. Postiglione ◽  
...  
Keyword(s):  
Developmental Stages ◽  
Brain Regions ◽  
Lacz Gene ◽  
Vestibular Organ ◽  
E Coli ◽  
Branchial Arches ◽  
Homeobox Protein ◽  
Derivatives Of ◽  
Delayed Ossification ◽  
Newborn Animals

The Dlx5 gene encodes a Distal-less-related DNA-binding homeobox protein first expressed during early embryonic development in anterior regions of the mouse embryo. In later developmental stages, it appears in the branchial arches, the otic and olfactory placodes and their derivatives, in restricted brain regions, in all extending appendages and in all developing bones. We have created a null allele of the mouse Dlx5 gene by replacing exons I and II with the E. coli lacZ gene. Heterozygous mice appear normal. Beta-galactosidase activity in Dlx5+/− embryos and newborn animals reproduces the known pattern of expression of the gene. Homozygous mutants die shortly after birth with a swollen abdomen. They present a complex phenotype characterised by craniofacial abnormalities affecting derivatives of the first four branchial arches, severe malformations of the vestibular organ, a delayed ossification of the roof of the skull and abnormal osteogenesis. No obvious defect was observed in the patterning of limbs and other appendages. The defects observed in Dlx5−/− mutant animals suggest multiple and independent roles of this gene in the patterning of the branchial arches, in the morphogenesis of the vestibular organ and in osteoblast differentiation.

Properties of transmission at a giant glutamatergic synapse in cerebellum: the mossy fiber-unipolar brush cell synapse

1995 ◽  
Vol 74 (1) ◽  
pp. 24-42 ◽  
Author(s):  
D. J. Rossi ◽  
S. Alford ◽  
E. Mugnaini ◽  
N. T. Slater
Keyword(s):  
Nmda Receptors ◽  
Rise Time ◽  
Extracellular Space ◽  
Granule Cells ◽  
Mossy Fiber ◽  
Lucifer Yellow ◽  
Synaptic Cleft ◽  
Brain Regions ◽  
Patch Clamp Recording ◽  
Brush Cells

1. The synaptic activation by mossy fibers (MFs) of unipolar brush cells (UBCs) in the vestibular cerebellum (nodulus and uvula) was examined using patch-clamp recording methods in thin, rat cerebellar slices with Lucifer yellow-filled pipettes for subsequent fluorescence microscopic verification of the cell morphology. 2. UBCs were distinguished from adjacent granule cells in thin cerebellar slices in the uvula and nodulus regions by their larger soma diameters and short dendritic brush, greater whole-cell capacitance, and a prolonged, biphasic excitatory postsynaptic current (EPSC) to stimulation of MFs. 3. Thin-section transmission electron micrographs of the MF-UBC synapse displayed an unusually extensive area of synaptic apposition estimated to measure 12-40 microns2. The majority of UBCs was innervated by a single MF. At high magnification, individual clusters of presynaptic vesicles could be discerned, separated by regions of presynaptic membrane lacking vesicles, but apposed to continuous regions of postsynaptic density. Thus, after release, transmitter diffusion from the synaptic cleft must traverse considerable stretches of postsynaptic membrane before escape into extracellular space. In contrast, MF-granule cell synapses in these cerebellar regions resembled glutamate synapses in other brain regions in that the total synaptic area measured < or = 4 microns2. These synaptic junctions were flanked by short stretches of unspecialized plasma membrane, providing a short (0.5 micron) diffusional path from the site of neurotransmitter release to a branch point of the extracellular space. 4. The MF-evoked EPSC in UBCs was composed of a fast (10-90% rise time: 0.70 ms) and slow (10-90% rise time: 395 ms; 10-90% decay time: 3.1 s) component. The fast component was blocked by the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate (AMPA/KA) antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (10 microM) and displayed linear current-voltage (I-V) relations in the presence or absence of external magnesium. 5. The slow EPSC was also mediated by glutamate receptors, but in most neurons both AMPA/KA and N-methyl-D-aspartate (NMDA) receptors contributed to the slow EPSC, with the contribution of NMDA receptors predominating in the majority of cells. Consequently, although all cells displayed linear I-V relations in Mg(2+)-free saline, cells in which the slow EPSC was predominently mediated by NMDA receptors exhibited voltage-dependent rectification in the presence of external Mg2+ (1 mM). 6. With increasing postnatal age (10-30 d), the contribution made to the slow EPSC by NMDA receptors declined, with a reciprocal increase in the contribution being made by AMPA/KA receptors.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Transient Activity Induces a Long-Lasting Increase in the Excitability of Olfactory Bulb Interneurons

2008 ◽  
Vol 99 (1) ◽  
pp. 187-199 ◽  
Author(s):  
Tsuyoshi Inoue ◽  
Ben W. Strowbridge
Keyword(s):  
Olfactory Bulb ◽  
Granule Cells ◽  
Receptor Activation ◽  
Brain Regions ◽  
Persistent Activity ◽  
Cellular Mechanisms ◽  
Calcium Dependent ◽  
Transient Activity ◽  
Olfactory Bulb Slices ◽  
Processing And Storage

Little is known about the cellular mechanisms that underlie the processing and storage of sensory in the mammalian olfactory system. Here we show that persistent spiking, an activity pattern associated with working memory in other brain regions, can be evoked in the olfactory bulb by stimuli that mimic physiological patterns of synaptic input. We find that brief discharges trigger persistent activity in individual interneurons that receive slow, subthreshold oscillatory input in acute rat olfactory bulb slices. A 2- to 5-Hz oscillatory input, which resembles the synaptic drive that the olfactory bulb receives during sniffing, is required to maintain persistent firing. Persistent activity depends on muscarinic receptor activation and results from interactions between calcium-dependent afterdepolarizations and low-threshold Ca spikes in granule cells. Computer simulations suggest that intrinsically generated persistent activity in granule cells can evoke correlated spiking in reciprocally connected mitral cells. The interaction between the intrinsic currents present in reciprocally connected olfactory bulb neurons constitutes a novel mechanism for synchronized firing in subpopulations of neurons during olfactory processing.

scholarly journals Acute stress enhances adult rat hippocampal neurogenesis and activation of newborn neurons via secreted astrocytic FGF2

eLife ◽  
2013 ◽  
Vol 2 ◽  
Author(s):  
Elizabeth D Kirby ◽  
Sandra E Muroy ◽  
Wayne G Sun ◽  
David Covarrubias ◽  
Megan J Leong ◽  
...  
Keyword(s):  
Basolateral Amygdala ◽  
Acute Stress ◽  
Memory Function ◽  
Brain Regions ◽  
Hippocampal Neurogenesis ◽  
Mammalian Brain ◽  
Stress Hormone ◽  
Adult Rat ◽  
Neural Stem Progenitor Cells ◽  
Newborn Neurons

Stress is a potent modulator of the mammalian brain. The highly conserved stress hormone response influences many brain regions, particularly the hippocampus, a region important for memory function. The effect of acute stress on the unique population of adult neural stem/progenitor cells (NPCs) that resides in the adult hippocampus is unclear. We found that acute stress increased hippocampal cell proliferation and astrocytic fibroblast growth factor 2 (FGF2) expression. The effect of acute stress occurred independent of basolateral amygdala neural input and was mimicked by treating isolated NPCs with conditioned media from corticosterone-treated primary astrocytes. Neutralization of FGF2 revealed that astrocyte-secreted FGF2 mediated stress-hormone-induced NPC proliferation. 2 weeks, but not 2 days, after acute stress, rats also showed enhanced fear extinction memory coincident with enhanced activation of newborn neurons. Our findings suggest a beneficial role for brief stress on the hippocampus and improve understanding of the adaptive capacity of the brain.

scholarly journals Cortical thickness and surface area correlates with cognitive dysfunction among first-episode psychosis patients

2016 ◽  
Vol 46 (10) ◽  
pp. 2145-2155 ◽  
Author(s):  
L. Haring ◽  
A. Müürsepp ◽  
R. Mõttus ◽  
P. Ilves ◽  
K. Koch ◽  
...  
Keyword(s):  
Structure Function ◽  
Surface Area ◽  
Cortical Thickness ◽  
Brain Structure ◽  
Brain Mri ◽  
Brain Regions ◽  
First Episode Psychosis ◽  
First Episode ◽  
Neurocognitive Performance ◽  
Episode Psychosis

BackgroundIn studies using magnetic resonance imaging (MRI), some have reported specific brain structure–function relationships among first-episode psychosis (FEP) patients, but findings are inconsistent. We aimed to localize the brain regions where cortical thickness (CTh) and surface area (cortical area; CA) relate to neurocognition, by performing an MRI on participants and measuring their neurocognitive performance using the Cambridge Neuropsychological Test Automated Battery (CANTAB), in order to investigate any significant differences between FEP patients and control subjects (CS).MethodExploration of potential correlations between specific cognitive functions and brain structure was performed using CANTAB computer-based neurocognitive testing and a vertex-by-vertex whole-brain MRI analysis of 63 FEP patients and 30 CS.ResultsSignificant correlations were found between cortical parameters in the frontal, temporal, cingular and occipital brain regions and performance in set-shifting, working memory manipulation, strategy usage and sustained attention tests. These correlations were significantly dissimilar between FEP patients and CS.ConclusionsSignificant correlations between CTh and CA with neurocognitive performance were localized in brain areas known to be involved in cognition. The results also suggested a disrupted structure–function relationship in FEP patients compared with CS.

scholarly journals Neuronal Substrates Underlying Performance Variability in Well-Trained Skillful Motor Task in Humans

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Nobuaki Mizuguchi ◽  
Shintaro Uehara ◽  
Satoshi Hirose ◽  
Shinji Yamamoto ◽  
Eiichi Naito
Keyword(s):  
Task Performance ◽  
Motor Skill ◽  
Brain Activity ◽  
Motor Task ◽  
Brain Regions ◽  
Anterior Cingulate ◽  
Cerebellar Hemisphere ◽  
Intensive Training ◽  
Performance Variability ◽  
The Right

Motor performance fluctuates trial by trial even in a well-trained motor skill. Here we show neural substrates underlying such behavioral fluctuation in humans. We first scanned brain activity with functional magnetic resonance imaging while healthy participants repeatedly performed a 10 s skillful sequential finger-tapping task. Before starting the experiment, the participants had completed intensive training. We evaluated task performance per trial (number of correct sequences in 10 s) and depicted brain regions where the activity changes in association with the fluctuation of the task performance across trials. We found that the activity in a broader range of frontoparietocerebellar network, including the bilateral dorsolateral prefrontal cortex (DLPFC), anterior cingulate and anterior insular cortices, and left cerebellar hemisphere, was negatively correlated with the task performance. We further showed in another transcranial direct current stimulation (tDCS) experiment that task performance deteriorated, when we applied anodal tDCS to the right DLPFC. These results indicate that fluctuation of brain activity in the nonmotor frontoparietocerebellar network may underlie trial-by-trial performance variability even in a well-trained motor skill, and its neuromodulation with tDCS may affect the task performance.

Changes in synaptic density in the subacute phase after ischemic stroke: A 11C-UCB-J PET/MR study

2021 ◽  
pp. 0271678X2110477
Author(s):  
Laura Michiels ◽  
Nathalie Mertens ◽  
Liselot Thijs ◽  
Ahmed Radwan ◽  
Stefan Sunaert ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Standardized Uptake Value ◽  
Brain Regions ◽  
Asymmetry Index ◽  
Cerebellar Hemisphere ◽  
Future Research ◽  
Stroke Patients ◽  
Synaptic Density ◽  
Positron Emission

Functional alterations after ischemic stroke have been described with Magnetic Resonance Imaging (MRI) and perfusion Positron Emission Tomography (PET), but no data on in vivo synaptic changes exist. Recently, imaging of synaptic density became available by targeting synaptic vesicle protein 2 A, a protein ubiquitously expressed in all presynaptic nerve terminals. We hypothesized that in subacute ischemic stroke loss of synaptic density can be evaluated with 11C-UCB-J PET in the ischemic tissue and that alterations in synaptic density can be present in brain regions beyond the ischemic core. We recruited ischemic stroke patients to undergo 11C-UCB-J PET/MR imaging 21 ± 8 days after stroke onset to investigate regional 11C-UCB-J SUVR (standardized uptake value ratio). There was a decrease (but residual signal) of 11C-UCB-J SUVR within the lesion of 16 stroke patients compared to 40 healthy controls (ratiolesion/controls = 0.67 ± 0.28, p = 0.00023). Moreover, 11C-UCB-J SUVR was lower in the non-lesioned tissue of the affected hemisphere compared to the unaffected hemisphere (ΔSUVR = −0.17, p = 0.0035). The contralesional cerebellar hemisphere showed a lower 11C-UCB-J SUVR compared to the ipsilesional cerebellar hemisphere (ΔSUVR = −0.14, p = 0.0048). In 8 out of 16 patients, the asymmetry index suggested crossed cerebellar diaschisis. Future research is required to longitudinally study these changes in synaptic density and their association with outcome.

Abstract WP64: Perfusion Imaging Can Identify Basilar Occlusion Patients With a Favorable Response to Thrombectomy

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Carlo W Cereda ◽  
Jeremy Heit ◽  
Giovanni Bianco ◽  
Marco Pileggi ◽  
Abid Qureshi ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Basilar Artery ◽  
Perfusion Imaging ◽  
Univariate Analysis ◽  
Brain Regions ◽  
Artery Occlusion ◽  
Posterior Circulation ◽  
Favorable Outcome ◽  
Cerebellar Hemisphere ◽  
Basilar Artery Occlusion

Introduction: Perfusion imaging can identify patients who respond favorably to endovascular therapy (EVT) in the anterior circulation; no data are available for the posterior circulation. We evaluated perfusion patterns, assessed with RAPID software, in a consecutive cohort of patients with basilar artery occlusion treated with EVT and assessed the association between reperfusion and favorable clinical outcome based on the perfusion profile. Hypothesis: We hypothesized that patients with limited regions of severe hypoperfusion (Tmax > 10s) would have a favorable response (mRS 0-2) to reperfusion (mTICI 2b-3) while patients with multiple critical brain regions severely hypoperfused would have poor outcome (mRS 4-6) despite reperfusion. Methods: From a multicenter cohort of perfusion imaging in posterior circulation stroke, we included patients with basilar artery occlusion and EVT. We pre-specified a Critical Area Perfusion Score (CAPS, 0 - 8 points) to identify severe hypoperfusion (Tmax >10s) in the following regions: inferior and/or superior cerebellar hemisphere (1-4 points), pons (2 points), midbrain/thalamus (2 points). We compared the outcome between reperfusers and non reperfusers based on the CAP score with univariate and multivariate analysis. Results: 38 patients met the inclusion criteria. Mean age was 63±17, 34% female, NIHSS 17±11. In patients who reperfused (n=30, 79%) 63% had favorable outcome, while no patient without reperfusion survived, p=0.003 OR=29 (95%CI 1.5-547). Ninety percent (19/21) of reperfused patients with CAPS ≤2 had a favorable outcome, while none of the 9 with reperfusion and a score >2 survived, p<0.001, OR=148 (95%CI 6.5-3,333). In univariate analysis, favorable outcome was associated with NIHSS OR=0.87 (95% CI 0.80-0.96), p=0.003, and mismatch volume OR=0.98 (95% CI 0.97-0.997) p=0.013. In the multivariate analysis, only CAPS was an independent predictor of favorable outcome. Conclusions: Patients with limited regions of severe hypoperfusion (Tmax > 10s) had a robust response to basilar artery EVT, however, all patients with multiple critical brain regions severely hypoperfused died despite successful reperfusion. Perfusion imaging profiles may help identify optimal patients for basilar EVT.

scholarly journals Identification of a β-Arrestin 2 Mutation Related to Autism by Whole-Exome Sequencing

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Yunfei Tang ◽  
Yamei Liu ◽  
Lei Tong ◽  
Shini Feng ◽  
Dongshu Du ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Developmental Stages ◽  
De Novo ◽  
Repetitive Behavior ◽  
Brain Regions ◽  
Autism Spectrum ◽  
Potential Contribution ◽  
De Novo Mutations ◽  
Whole Exome

Autism spectrum disorder (ASD) is a complex neurological disease characterized by impaired social communication and interaction skills, rigid behavior, decreased interest, and repetitive activities. The disease has a high degree of genetic heterogeneity, and the genetic cause of ASD in many autistic individuals is currently unclear. In this study, we report a patient with ASD whose clinical features included social interaction disorder, communication disorder, and repetitive behavior. We examined the patient’s genetic variation using whole-exome sequencing technology and found new de novo mutations. After analysis and evaluation, ARRB2 was identified as a candidate gene. To study the potential contribution of the ARRB2 gene to the human brain development and function, we first evaluated the expression profile of this gene in different brain regions and developmental stages. Then, we used weighted gene coexpression network analysis to analyze the associations between ARRB2 and ASD risk genes. Additionally, the spatial conformation and stability of the ARRB2 wild type and mutant proteins were examined by simulations. Then, we further established a mouse model of ASD. The results showed abnormal ARRB2 expression in the mouse ASD model. Our study showed that ARRB2 may be a risk gene for ASD, but the contribution of de novo ARRB2 mutations to ASD is unclear. This information will provide references for the etiology of ASD and aid in the mechanism-based drug development and treatment.

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