Physiological Processes In Brain Research Articles

88. The effect of EMF treatment at the low frequencies of 10 and 30 Hz on spatial memory of mice in the Morris water maze

Objective: Studies show that low-frequency electromagnetic fields (EMFs) can have effects on brain physiological processes. Thus the aim of this study was to determine the effect of a very low frequency EMF (10 Hz, 2 μT) on the spatial memory of mice using the Morris water maze (MWM).

A nonsynaptic mechanism underlying interictal discharges in human epileptic neocortex

Very fast oscillations (VFOs, >80 Hz) are important for physiological brain processes and, in excess, with certain epilepsies. Putative mechanisms for VFO include interneuron spiking and network activity in coupled pyramidal cell axons. It is not known whether either, or both, of these apply in pathophysiological conditions. Spontaneously occurring interictal discharges occur in human tissue in vitro, resected from neocortical epileptic foci. VFO associated with these discharges was manifest in both field potential and, with phase delay, in excitatory synaptic inputs to fast spiking interneurons. Recruitment of somatic pyramidal cell and interneuron spiking was low, with no correlation between VFO power and synaptic inputs to principal cells. Reducing synaptic inhibition failed to affect VFO occurrence, but they were abolished by reduced gap junction conductance. These data suggest a lack of a causal role for interneurons, and favor a nonsynaptic pyramidal cell network origin for VFO in epileptic human neocortex.

Targeting murine heart and brain: visualisation conditions for multi-pinhole SPECT with (99m)Tc- and (123)I-labelled probes.

PurposeThe study serves to optimise conditions for multi-pinhole SPECT small animal imaging of 123I- and 99mTc-labelled radiopharmaceuticals with different distributions in murine heart and brain and to investigate detection and dose range thresholds for verification of differences in tracer uptake.MethodsA Triad 88/Trionix system with three 6-pinhole collimators was used for investigation of dose requirements for imaging of the dopamine D2 receptor ligand [123I]IBZM and the cerebral perfusion tracer [99mTc]HMPAO (1.2–0.4 MBq/g body weight) in healthy mice. The fatty acid [123I]IPPA (0.94 ± 0.05 MBq/g body weight) and the perfusion tracer [99mTc]sestamibi (3.8 ± 0.45 MBq/g body weight) were applied to cardiomyopathic mice overexpressing the prostaglandin EP3 receptor.ResultsIn vivo imaging and in vitro data revealed 45 kBq total cerebral uptake and 201 kBq cardiac uptake as thresholds for visualisation of striatal [123I]IBZM and of cardiac [99mTc]sestamibi using 100 and 150 s acquisition time, respectively. Alterations of maximal cerebral uptake of [123I]IBZM by >20% (116 kBq) were verified with the prerequisite of 50% striatal of total uptake. The labelling with [99mTc]sestamibi revealed a 30% lower uptake in cardiomyopathic hearts compared to wild types. [123I]IPPA uptake could be visualised at activity doses of 0.8 MBq/g body weight.ConclusionMulti-pinhole SPECT enables detection of alterations of the cerebral uptake of 123I- and 99mTc-labelled tracers in an appropriate dose range in murine models targeting physiological processes in brain and heart. The thresholds of detection for differences in the tracer uptake determined under the conditions of our experiments well reflect distinctions in molar activity and uptake characteristics of the tracers.Electronic supplementary materialThe online version of this article (doi:10.1007/s00259-009-1142-9) contains supplementary material, which is available to authorized users.

Engineered lentiviral vector targeting astrocytes In vivo

Astrocytes are involved in key physiological brain processes, such as glutamatergic transmission and energy metabolism, often altered in neurodegenerative diseases. Targeted gene expression in astrocytes is needed to assess the contribution of these cells to physiological processes and for the development of new therapeutic strategies. However, most of the viral vectors currently used for gene transfer in the central nervous system (CNS) are highly neurotropic. We used mokola pseudotyping to shift the tropism of lentiviral vectors toward astrocytes and a detargeting strategy with miRNA to eliminate residual expression in neuronal cells. In primary cultures, we showed that incorporating target sequences for the neuron-specific miR124 effectively abolished transgene expression in neurons post-transcriptionally. Targeted expression of the LacZ reporter gene in astrocytes was achieved in the hippocampus, striatum, and cerebellum of the adult mouse in vivo. As a proof-of-principle, this new lentiviral vector was used to either overexpress or downregulate (RNA interference) the glial glutamate transporter GLAST into striatal astrocytes in vivo. These vectors provide new opportunities for cell type-specific gene transfer in the CNS.

Artifactual time‐course correlations in echo‐planar fMRI with implications for studies of brain function

AbstractBrain function is widely investigated with functional magnetic resonance imaging (fMRI) in humans and animals. In fMRI, the time courses of voxels typically reflect the local blood‐oxygen level, which is taken as an indicator of neuronal activity. Voxel time‐course correlations are often explicitly modeled and interpreted in terms of neuronal interactions. They also affect standard analyses that do not explicitly target neuronal interactions. As a consequence, time‐course correlations between voxels influence conclusions about cognitive and physiological brain processes in many studies. However, voxel correlations are known to arise not only from cognitive and physiological processes, but also as artifacts of fMRI techniques such as the commonly used echoplanar imaging. We empirically demonstrate this phenomenon by plotting time‐course correlation as a function of voxel separation for a human brain in resting state and for a water‐filled sphere (called a “phantom”). The phantom served as a test object known not to contain any interacting neuronal systems. The plots for brain and phantom are surprisingly similar. The correlational structure found in the phantom must be artifactual. Artifactual correlations spanning many centimeters occur within and between different imaging slices. Correlations between voxel time courses do not necessarily reflect brain processes. Instead, fMRI is affected by artifactual correlations, which are very strong for neighboring voxels and clearly present even at large distances. This needs to be taken into account in the neuroscientific interpretation of voxel correlations. © 2008 Wiley Periodicals, Inc. Int J Imaging Syst Technol, 18, 345–349, 2008

Pig brain stereotaxic standard space: Mapping of cerebral blood flow normative values and effect of MPTP-lesioning

The analysis of physiological processes in brain by position emission tomography (PET) is facilitated when images are spatially normalized to a standard coordinate system. Thus, PET activation studies of human brain frequently employ the common stereotaxic coordinates of Talairach. We have developed an analogous stereotaxic coordinate system for the brain of the Göttingen miniature pig, based on automatic co-registration of magnetic resonance (MR) images obtained in 22 male pigs. The origin of the pig brain stereotaxic space (0, 0, 0) was arbitrarily placed in the centroid of the pineal gland as identified on the average MRI template. The orthogonal planes were imposed using the line between stereotaxic zero and the optic chiasm. A series of mean MR images in the coronal, sagittal and horizontal planes were generated. To test the utility of the common coordinate system for functional imaging studies of minipig brain, we calculated cerebral blood flow (CBF) maps from normal minipigs and from minipigs with a syndrome of parkisonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-poisoning. These maps were transformed from the native space into the common stereotaxic space. After global normalization of these maps, an undirected search for differences between the groups was then performed using statistical parametric mapping. Using this method, we detected a statistically significant focal increase in CBF in the left cerebellum of the MPTP-lesioned group. We expect the present approach to be of general use in the statistical parametric mapping of CBF and other physiological parameters in living pig brain.

Peroxisomes and PPARs in cultured neural cells.

The importance of peroxisomes in central nervous system (CNS) comes from the observation that in several peroxisomal disorders, such as Zellweger syndrome, Adrenoleukodystrophy, Rhizomelyc chondrodysplasia punctata etc, severe neurological impairments were observed. They have been involved in several physiological processes in brain, such as protection against reactive oxygen species (ROS), myelinogenesis and very long chain fatty acid metabolism.KeywordsRetinoic Acid ReceptorZellweger SyndromePeroxisomal EnzymePeroxisomal DisorderSevere Neurological ImpairmentThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

C-fos expression in brains of patients with Down syndrome.

c-fos is a protooncogene serving in multiple physiological processes in brain from signalling to proliferation and synaptic plasticity. We therefore decided to determine this transcription factor in control and Down Syndrome (DS) brain with the Rationale that c-fos may be linked to brain damage in DS. We determined mRNA steady state levels in frontal, parietal, occipital, temporal cortex and cerebellum of 9 patients with DS and 9 controls using RT-PCT. Significantly increased levels of mRNA c-fos normalized versus the housekeeping gene beta-actin mRNA were found in frontal, parietal and temporal cortex of DS brain. c-fox mRNA levels comparable to controls were found in occipital cortex and cerebellum. Deteriorated c-fos expression in the individual brain regions may be linked to increased apoptosis and neurodegeneration, overexcitation by excitatory amino acids of reactive oxygen species.