Developmental Time Courses in the Brain and Kidney of Two Enzymes that Oxidize γ-Hydroxybutyrate

AbstractFundamental differences between perception and cognition argue that the distinction can be maintained independently of cognitive penetrability. The core processes of cognition can be integrated under the theory of relational knowledge. The distinguishing properties include symbols and an operating system, structure-consistent mapping between representations, construction of representations in working memory that enable generation of inferences, and different developmental time courses.

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Use of [3H]methylglucose and [14C]iodoantipyrine to determine kinetic parameters of glucose transport in rat brain

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1997.272.1.r163 ◽

1997 ◽

Vol 272 (1) ◽

pp. R163-R171

Author(s):

K. Mori ◽

M. Maeda

Keyword(s):

Blood Flow ◽

Surface Area ◽

Glucose Transport ◽

Tissue Samples ◽

Arterial Blood ◽

Permeability Surface ◽

Time Courses ◽

Area Product ◽

Menten Kinetic ◽

The Brain

Local maximal velocities of transport (Tmax) and the half-maximum transport constants (KT) for glucose transport across the blood-brain barrier have been determined in local regions of the brain in normal conscious rats. [14C]iodoantipyrine and [3H]methylglucose were infused together intravenously for 2 min in rats with plasma glucose concentrations maintained at different levels, and the time courses of the tracer levels in arterial blood were measured. Local 14C and 3H concentrations were then measured in tissue samples dissected from the frozen brains. By comparing the transport-limited uptake of [3H]methylglucose with the blood flow-limited uptake of [14C]iodoantipyrine, the value of m, a factor between 0 and 10 that accounts for diffusion and/or transport limitations, was derived, and from the equation, m = 1 - PS/F (where PS is capillary permeability-surface area product and F is cerebral blood flow), the permeability-capillary surface area for methylglucose was calculated (S. S. Kety. Pharmacol. Rev. 3: 1-41, 1951). Values for Tmax and KT for glucose were calculated by application of Michaelis-Menten kinetic relationships adapted for the competition for transport between glucose and methylglucose. Tmax was determined in three representative gray structures and one white structure of the brain: Tmax was 5.3 +/- 0.3 (SD) mumol.g-1.min-1 in the gray structures and 4.3 mumol.g-1.min-1 in the white structure. KT was 3.6 +/- 0.4 (SD) mM in the gray structures and 5.9 mM in the white structure. This approach allows the simultaneous determination of local values of Tmax and KT for glucose and the rates of blood flow in various regions of the brain in conscious animals.

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Prediction of motor recovery using indirect connectivity in a lesion network after ischemic stroke

Therapeutic Advances in Neurological Disorders ◽

10.1177/1756286420925679 ◽

2020 ◽

Vol 13 ◽

pp. 175628642092567

Author(s):

Jungsoo Lee ◽

Eunhee Park ◽

Ahee Lee ◽

Won Hyuk Chang ◽

Dae-Shik Kim ◽

...

Keyword(s):

Prediction Model ◽

Motor Function ◽

Brain Network ◽

Reference Network ◽

Lesion Volume ◽

Motor Impairments ◽

Rehabilitation Programs ◽

Time Courses ◽

The Impact ◽

The Brain

Background: Recovery prediction can assist in the planning for impairment-focused rehabilitation after a stroke. This study investigated a new prediction model based on a lesion network analysis. To predict the potential for recovery, we focused on the next link-step connectivity of the direct neighbors of a lesion. Methods: We hypothesized that this connectivity would contribute to recovery after stroke onset. Each lesion in a patient who had suffered a stroke was transferred to a healthy subject. First link-step connectivity was identified by observing voxels functionally connected to each lesion. Next (second) link-step connectivity of the first link-step connectivity was extracted by calculating statistical dependencies between time courses of regions not directly connected to a lesion and regions identified as first link-step connectivity. Lesion impact on second link-step connectivity was quantified by comparing the lesion network and reference network. Results: The lower the impact of a lesion was on second link-step connectivity in the brain network, the better the improvement in motor function during recovery. A prediction model containing a proposed predictor, initial motor function, age, and lesion volume was established. A multivariate analysis revealed that this model accurately predicted recovery at 3 months poststroke ( R 2 = 0.788; cross-validation, R 2 = 0.746, RMSE = 13.15). Conclusion: This model can potentially be used in clinical practice to develop individually tailored rehabilitation programs for patients suffering from motor impairments after stroke.

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Predicting Brain Occupancy from Plasma Levels using PET: Superiority of Combining Pharmacokinetics with Pharmacodynamics while Modeling the Relationship

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2011.180 ◽

2011 ◽

Vol 32 (4) ◽

pp. 759-768 ◽

Cited By ~ 15

Author(s):

Euitae Kim ◽

Oliver D Howes ◽

Bo-Hyung Kim ◽

Jae Min Jeong ◽

Jae Sung Lee ◽

...

Keyword(s):

Dopamine Receptor ◽

Receptor Occupancy ◽

Analysis Approach ◽

Reliable Prediction ◽

Positron Emission ◽

Time Courses ◽

The Relationship ◽

The Brain ◽

Serial Measurements ◽

Hysteresis Characteristics

Positron emission tomography (PET) studies of dopamine receptor occupancy can be used to assess dosing of antipsychotics. Typically, studies of antipsychotics have applied pharmacodynamic (PD) modeling alone to characterize the relationship between antipsychotic dose and its effect on the brain. However, a limitation of this approach is that it does not account for the discrepancy between the time courses of plasma concentration and receptor occupancy by antipsychotics. Combined pharmacokinetic—PD (PK—PD) modeling, by incorporating the time dependence of occupancy, is better suited for the reliable analysis of the concentration—occupancy relationship. To determine the effect of time on the concentration—occupancy relationship as a function of analysis approach, we measured dopamine receptor occupancy after the administration of aripiprazole using [11C]raclopride PET and obtained serial measurements of the plasma aripiprazole concentration in 18 volunteers. We then developed a PK—PD model for the relationship, and compared it with conventional approach (PD modeling alone). The hysteresis characteristics were observed in the competitor concentration—occupancy relationship and the value of EC50 was different according to the analysis approach ( EC50 derived from PD modeling alone = 11.1 ng/mL (95% confidence interval (CI) = 10.1 to 12.1); while that derived from combined PK—PD modeling = 8.63 ng/mL (95% CI = 7.75 to 9.51)). This finding suggests that PK—PD modeling is required to obtain reliable prediction of brain occupancy by antipsychotics.

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Late maturation of backward masking in auditory cortex

Journal of Neurophysiology ◽

10.1152/jn.00114.2018 ◽

2018 ◽

Vol 120 (4) ◽

pp. 1558-1571

Author(s):

Michelle M. Mattingly ◽

Brittany M. Donell ◽

Merri J. Rosen

Keyword(s):

Language Processing ◽

Speech Processing ◽

Dynamic Range ◽

Developmental Time ◽

Mongolian Gerbils ◽

Backward Masking ◽

Selective Listening ◽

Age Related ◽

Time Courses ◽

Short Signal

Speech perception relies on the accurate resolution of brief, successive sounds that change rapidly over time. Deficits in the perception of such sounds, indicated by a reduced ability to detect signals during auditory backward masking, strongly relate to language processing difficulties in children. Backward masking during normal development has a longer maturational trajectory than many other auditory percepts, implicating the involvement of central auditory neural mechanisms with protracted developmental time courses. Despite the importance of this percept, its neural correlates are not well described at any developmental stage. We therefore measured auditory cortical responses to masked signals in juvenile and adult Mongolian gerbils and quantified the detection ability of individual neurons and neural populations in a manner comparable with psychoacoustic measurements. Perceptually, auditory backward masking manifests as higher thresholds for detection of a short signal followed by a masker than for the same signal in silence. Cortical masking was driven by a combination of suppressed responses to the signal and a reduced dynamic range available for signal detection in the presence of the masker. Both coding elements contributed to greater masked threshold shifts in juveniles compared with adults, but signal-evoked firing suppression was more pronounced in juveniles. Neural threshold shifts were a better match to human psychophysical threshold shifts when quantified with a longer temporal window that included the response to the delayed masker, suggesting that temporally selective listening may contribute to age-related differences in backward masking. NEW & NOTEWORTHY In children, auditory detection of backward masked signals is immature well into adolescence, and detection deficits correlate with problems in speech processing. Our auditory cortical recordings reveal immature backward masking in adolescent animals that mirrors the prolonged development seen in children. This is driven by both signal-evoked suppression and dynamic range reduction. An extended window of analysis suggests that differences in temporally focused listening may contribute to late maturing thresholds for backward masked signals.

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Ambient temperature modulates hypoxic-induced changes in rat body temperature and activity differentially

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.2001.280.4.r1190 ◽

2001 ◽

Vol 280 (4) ◽

pp. R1190-R1196 ◽

Cited By ~ 16

Author(s):

B. Bishop ◽

G. Silva ◽

J. Krasney ◽

H. Nakano ◽

A. Roberts ◽

...

Keyword(s):

Body Temperature ◽

Ambient Temperature ◽

Induced Responses ◽

Brain Pathology ◽

Level Of Activity ◽

Time Courses ◽

Induced Changes ◽

Subsequent Rise ◽

The Brain

When rats, acclimated to an ambient temperature (Ta) of 29°C, are exposed to 10% O2 for 63 h, the circadian rhythms of body temperature (Tb) and level of activity (La) are abolished, Tb falls to a hypothermic nadir followed by a climb to a hyperthermic peak, Laremains depressed (Bishop B, Silva G, Krasney J, Salloum A, Roberts A, Nakano H, Shucard D, Rifkin D, and Farkas G. Am J Physiol Regulatory Integrative Comp Physiol 279: R1378–R1389, 2000), and overt brain pathology is detected (Krasney JA, Farkas G, Shucard DW, Salloum AC, Silva G, Roberts A, Rifkin D, Bishop B, and Rubio A. Soc Neurosci Abstr 25: 581, 1999). To determine the role of Ta in these hypoxic-induced responses, Tb and La data were detected by telemetry every 15 min for 48 h on air, followed by 63 h on 10% O2 from rats acclimated to 25 or 21°C. Magnitudes and rates of decline in Tb after onset of hypoxia were inversely proportional to Ta, whereas magnitudes and rates of Tb climb after the hypothermic nadir were directly proportional to Ta. No hyperthermia, so prominent at 29°C, occurred at 25 or 21°C. The hypoxic depression of La was least at 21°C and persisted throughout the hypoxia. In contrast, Ta was a strong determinant of the magnitudes and time courses of the initial fall and subsequent rise in Tb. We propose that the absence of hyperthermia at 21 and 25°C as well as a persisting hypothermia may protect the brain from overt pathology.

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Manganese Dynamics in Mouse Brain After Systemic MnCl2 Administration for Activation-Induced Manganese-Enhanced MRI

Frontiers in Neural Circuits ◽

10.3389/fncir.2021.787692 ◽

2021 ◽

Vol 15 ◽

Author(s):

Hiroki Tanihira ◽

Tomonori Fujiwara ◽

Satomi Kikuta ◽

Noriyasu Homma ◽

Makoto Osanai

Keyword(s):

Control Level ◽

Brain Parenchyma ◽

Systemic Administration ◽

High Concentration ◽

Neural Activities ◽

Enhanced Mri ◽

Longitudinal Relaxation ◽

Time Courses ◽

Manganese Enhanced Mri ◽

The Brain

Activation-induced manganese-enhanced MRI (AIM-MRI) is an attractive tool for non-invasively mapping whole brain activities. Manganese ions (Mn2+) enter and accumulate in active neurons via calcium channels. Mn2+ shortens the longitudinal relaxation time (T1) of H+, and the longitudinal relaxation rate R1 (1/T1) is proportional to Mn2+ concentration. Thus, AIM-MRI can map neural activities throughout the brain by assessing the R1 map. However, AIM-MRI is still not widely used, partially due to insufficient information regarding Mn2+ dynamics in the brain. To resolve this issue, we conducted a longitudinal study looking at manganese dynamics after systemic administration of MnCl2 by AIM-MRI with quantitative analysis. In the ventricle, Mn2+ increased rapidly within 1 h, remained high for 3 h, and returned to near control levels by 24 h after administration. Microdialysis showed that extracellular Mn returned to control levels by 4 h after administration, indicating a high concentration of extracellular Mn2+ lasts at least about 3 h after administration. In the brain parenchyma, Mn2+ increased slowly, peaked 24–48 h after administration, and returned to control level by 5 days after a single administration and by 2 weeks after a double administration with a 24-h interval. These time courses suggest that AIM-MRI records neural activity 1–3 h after MnCl2 administration, an appropriate timing of the MRI scan is in the range of 24–48 h following systemic administration, and at least an interval of 5 days or a couple of weeks for single or double administrations, respectively, is needed for a repeat AIM-MRI experiment.

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The Development of Multisensory Integration in the Brain

Perception ◽

10.1068/v970014 ◽

1997 ◽

Vol 26 (1_suppl) ◽

pp. 35-35 ◽

Cited By ~ 1

Author(s):

M T Wallace

Keyword(s):

Multisensory Integration ◽

Time Course ◽

Receptive Fields ◽

Developmental Time ◽

Response Latencies ◽

Sensory Stimuli ◽

Sensory Inputs ◽

Response Enhancement ◽

Sensory Responses ◽

The Brain

Multisensory integration in the superior colliculus (SC) of the cat requires a protracted postnatal developmental time course. Kittens 3 – 135 days postnatal (dpn) were examined and the first neuron capable of responding to two different sensory inputs (auditory and somatosensory) was not seen until 12 dpn. Visually responsive multisensory neurons were not encountered until 20 dpn. These early multisensory neurons responded weakly to sensory stimuli, had long response latencies, large receptive fields, and poorly developed response selectivities. Most striking, however, was their inability to integrate cross-modality cues in order to produce the significant response enhancement or depression characteristic of these neurons in adults. The incidence of multisensory neurons increased gradually over the next 10 – 12 weeks. During this period, sensory responses became more robust, latencies shortened, receptive fields decreased in size, and unimodal selectivities matured. The first neurons capable of cross-modality integration were seen at 28 dpn. For the following two months, the incidence of such integrative neurons rose gradually until adult-like values were achieved. Surprisingly, however, as soon as a multisensory neuron exhibited this capacity, most of its integrative features were indistinguishable from those in adults. Given what is known about the requirements for multisensory integration in adult animals, this observation suggests that the appearance of multisensory integration reflects the onset of functional corticotectal inputs.

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G-protein-linked signal transduction systems control development in Dictyostelium

Development ◽

10.1242/dev.107.supplement.75 ◽

1989 ◽

Vol 107 (Supplement) ◽

pp. 75-80

Author(s):

R. L. Johnson ◽

R. Gundersen ◽

P. Lilly ◽

G. S. Pitt ◽

M. Pupillo ◽

...

Keyword(s):

G Protein ◽

Fold Increase ◽

Developmental Time ◽

Developmental Program ◽

C Terminus ◽

Specific Antisera ◽

Functional Defect ◽

Time Courses ◽

Kinetics Of ◽

Signal Transduction Systems

G-protein-linked cAMP receptors play an essential role in Dictyostelium development. The cAMP receptors are proposed to have seven transmembrane domains and a cytoplasmic C-terminal region. Overexpression of the receptor in cells, when the endogenous receptor is not present, results in a 10- to 50-fold increase in cAMPbinding sites. Antisense cell lines, which lack cAMP receptors, do not enter the developmental program. Ligand-induced phosphorylation is proposed to occur on serine and threonine residues in the receptor C-terminus. The kinetics of receptor phosphorylation and dephosphorylation correlate closely with the shift of receptor mobility and the adaptation of several cAMPinduced responses. Two a-subunits, G-α-1 and G-α-2, have been cloned and specific antisera developed against each. Both subunits are expressed as multiple RNAs with different developmental time courses. The mutant Frigid A has a functional defect in G-α-2 which prevents it from entering development. We propose that Gprotein-linked receptor systems will be a major component in the development of many organisms.

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