Metabolic Maturation of the Brain: A Study of Local Cerebral Glucose Utilization in the Developing Cat

Previously, using positron emission tomography (PET), we showed that local cerebral metabolic rates for glucose (lCMRglc) in children undergo dynamic maturational trends before reaching adult values. In order to develop an animal model that can be used to explore the biological significance of the different segments of the lCMRglc maturational curve, we measured lCMRglc in kittens at various stages of postnatal development and in adult cats using quantitative [14C]2-deoxyglucose autoradiography. In the kitten, very low lCMRglc levels (0.14 to 0.53 μmol min−1 g−1) were seen during the first 15 days of life, with phylogenetically older brain regions being generally more metabolically mature than newer structures. After 15 days of age, many brain regions (particularly telencephalic structures) underwent sharp increases of lCMRglc to reach, or exceed, adult rates by 60 days. This developmental period (15 to 60 days) corresponds to the time of rapid synaptic proliferation known to occur in the cat. At 90 and 120 days, a slight decline in lCMRglc was observed, but this was followed by a second, larger peak occurring at about 180 days, when sexual maturation occurs in the cat. Only after 180 days did lCMRglc decrease to reach final adult values (0.21 to 2.04 μmol min−1 g−1). In general, there was good correlation between the metabolic maturation of various neuroanatomical regions and the emergence of behaviors mediated by the specific region. At least in the kitten visual cortex, which has been extensively studied with respect to developmental plasticity, the “critical period” corresponded to that portion of the lCMRglc maturational curve surrounding the 60-day metabolic peak. These normal maturational lCMRglc data will serve as baseline values with which to compare anatomical and metabolic plasticity changes induced by age-related lesions in the cat.

Download Full-text

Pain Detection and the Privacy of Subjective Experience

American Journal of Law & Medicine ◽

10.1177/009885880703300212 ◽

2007 ◽

Vol 33 (2-3) ◽

pp. 433-456 ◽

Cited By ~ 22

Author(s):

Adam J. Kolber

Keyword(s):

Subjective Experience ◽

Brain Regions ◽

Physical Pain ◽

Medical Evidence ◽

Functional Magnetic Resonance ◽

Positron Emission ◽

Pain Symptoms ◽

The Brain ◽

Insight Into ◽

Neuroimaging Techniques

A neurologist with abdominal pain goes to see a gastroenterologist for treatment. The gastroenterologist asks the neurologist where it hurts. The neurologist replies, “In my head, of course.” Indeed, while we can feel pain throughout much of our bodies, pain signals undergo most of their processing in the brain. Using neuroimaging techniques like functional magnetic resonance imaging (“fMRI”) and positron emission tomography (“PET”), researchers have more precisely identified brain regions that enable us to experience physical pain. Certain regions of the brain's cortex, for example, increase in activation when subjects are exposed to painful stimuli. Furthermore, the amount of activation increases with the intensity of the painful stimulus. These findings suggest that we may be able to gain insight into the amount of pain a particular person is experiencing by non-invasively imaging his brain.Such insight could be particularly valuable in the courtroom where we often have no definitive medical evidence to prove or disprove claims about the existence and extent of pain symptoms.

Download Full-text

Metabolic Plasticity of Astrocytes and Aging of the Brain

International Journal of Molecular Sciences ◽

10.3390/ijms20040941 ◽

2019 ◽

Vol 20 (4) ◽

pp. 941 ◽

Cited By ~ 11

Author(s):

Mitsuhiro Morita ◽

Hiroko Ikeshima-Kataoka ◽

Marko Kreft ◽

Nina Vardjan ◽

Robert Zorec ◽

...

Keyword(s):

Systemic Circulation ◽

Brain Parenchyma ◽

Acid Oxidation ◽

Normal Brain ◽

Atp Production ◽

Metabolic Plasticity ◽

Neuronal Synapses ◽

Age Related ◽

Pathologic Processes ◽

The Brain

As part of the blood-brain-barrier, astrocytes are ideally positioned between cerebral vasculature and neuronal synapses to mediate nutrient uptake from the systemic circulation. In addition, astrocytes have a robust enzymatic capacity of glycolysis, glycogenesis and lipid metabolism, managing nutrient support in the brain parenchyma for neuronal consumption. Here, we review the plasticity of astrocyte energy metabolism under physiologic and pathologic conditions, highlighting age-dependent brain dysfunctions. In astrocytes, glycolysis and glycogenesis are regulated by noradrenaline and insulin, respectively, while mitochondrial ATP production and fatty acid oxidation are influenced by the thyroid hormone. These regulations are essential for maintaining normal brain activities, and impairments of these processes may lead to neurodegeneration and cognitive decline. Metabolic plasticity is also associated with (re)activation of astrocytes, a process associated with pathologic events. It is likely that the recently described neurodegenerative and neuroprotective subpopulations of reactive astrocytes metabolize distinct energy substrates, and that this preference is supposed to explain some of their impacts on pathologic processes. Importantly, physiologic and pathologic properties of astrocytic metabolic plasticity bear translational potential in defining new potential diagnostic biomarkers and novel therapeutic targets to mitigate neurodegeneration and age-related brain dysfunctions.

Download Full-text

29 POSITRON EMISSION TOMOGRAPHY IMAGING OF BRAIN METABOLISM AND DOPAMINERGIC NEURON DESTRUCTION IN PARKINSON'S DISEASE MODEL PIG

Reproduction Fertility and Development ◽

10.1071/rdv29n1ab29 ◽

2017 ◽

Vol 29 (1) ◽

pp. 122

Author(s):

H. J. Oh ◽

J. Moon ◽

G. A. Kim ◽

S. Lee ◽

S. H. Paek ◽

...

Keyword(s):

Positron Emission Tomography ◽

Dopaminergic Neuron ◽

Brain Metabolism ◽

Brain Research ◽

Brain Regions ◽

Emission Tomography ◽

Positron Emission ◽

Significant Difference ◽

And Control ◽

The Brain

Due to similarities between human and porcine, pigs have been proposed as an excellent experimental animal for human medical research. Especially in paediatric brain research, piglets share similarities with human infants in the extent of peak brain growth at the time of birth and the growth pattern of brain. Thus, these findings have supported the wider use of pigs rather than rodents in neuroscience research. Previously, we reported the production of porcine model of Parkinson's disease (PD) by nuclear transfer using donor cell that had been stably infected with lentivirus containing the human α-synuclein gene. The purpose of this study was to determine the alternation of brain metabolism and dopaminergic neuron destruction using noninvasive method in a 2-yr-old PD model and a control pig. The positron emission tomography (PET) scan was done using Biograph TruePoint40 with a TrueV (Siemens, Munich, Germany). The [18F]N-(3-fluoropropyl)-2β-carbomethoxy-3β-(4-iodophenyl) nortropane (FP-CIT) was administrated via the ear vein. Static images of the brain for 15 min were acquired from 2 h after injection. The 18F-fluorodeoxy-D-glucose PET (18F-FDG PET) images of the brain were obtained for 15 min at 45 min post-injection. Computed tomography (CT) scan and magnetic resonance imaging (MRI) were performed at the same location of the brain. In both MRI and CT images, there was no difference in brain regions between PD model and control pigs. However, administration of [18F]FP-CIT was markedly decreased in the bilateral putamen of the PD model pig compared with the control pigs. Moreover, [18F]FP-CIT administration was asymmetrical in the PD model pig but it was symmetrical in control pigs. Regional brain metabolism was also assessed and there was no significant difference in cortical metabolism of PD model and control pigs. We demonstrated that PET imaging could provide a foundation for translational Parkinson neuroimaging in transgenic pigs. In the present study, a 2-yr-old PD model pig showed dopaminergic neuron destruction in brain regions. Therefore, PD model pig expressing human α-synuclein gene would be an efficient model for human PD patients. This study was supported by Korea IPET (#311011–05–5-SB010), Research Institute for Veterinary Science, TS Corporation and the BK21 plus program.

Download Full-text

Medial Orbitofrontal Cortex Is Associated with Fatigue Sensation

Neurology Research International ◽

10.1155/2010/671421 ◽

2010 ◽

Vol 2010 ◽

pp. 1-5 ◽

Cited By ~ 21

Author(s):

Seiki Tajima ◽

Shigeyuki Yamamoto ◽

Masaaki Tanaka ◽

Yosky Kataoka ◽

Masao Iwase ◽

...

Keyword(s):

Positron Emission Tomography ◽

Orbitofrontal Cortex ◽

Brain Region ◽

Statistical Parametric Mapping ◽

Brain Regions ◽

Mapping Method ◽

Emission Tomography ◽

Neural Basis ◽

Positron Emission ◽

The Brain

Fatigue is an indispensable bioalarm to avoid exhaustive state caused by overwork or stresses. It is necessary to elucidate the neural mechanism of fatigue sensation for managing fatigue properly. We performedH2O 15positron emission tomography scans to indicate neural activations while subjects were performing 35-min fatigue-inducing task trials twice. During the positron emission tomography experiment, subjects performed advanced trail-making tests, touching the target circles in sequence located on the display of a touch-panel screen. In order to identify the brain regions associated with fatigue sensation, correlation analysis was performed using statistical parametric mapping method. The brain region exhibiting a positive correlation in activity with subjective sensation of fatigue, measured immediately after each positron emission tomography scan, was located in medial orbitofrontal cortex (Brodmann's area 10/11). Hence, the medial orbitofrontal cortex is a brain region associated with mental fatigue sensation. Our findings provide a new perspective on the neural basis of fatigue.

Download Full-text

Local Cerebral Glucose Utilization in Normal Female Rats: Variations during the Estrous Cycle and Comparison with Males

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.1985.54 ◽

1985 ◽

Vol 5 (3) ◽

pp. 393-400 ◽

Cited By ~ 44

Author(s):

Astrid Nehlig ◽

Linda J. Porrino ◽

Alison M. Crane ◽

Louis Sokoloff

Keyword(s):

Estrous Cycle ◽

Glucose Utilization ◽

Brain Regions ◽

Female Rats ◽

Male Rats ◽

Normal Male ◽

Normal Female ◽

Female Rat ◽

Males And Females ◽

The Brain

The quantitative 2-[14C]deoxyglucose autoradiographic method was used to study the fluctuations of energy metabolism in discrete brain regions of female rats during the estrous cycle. A consistent though statistically nonsignificant cyclic variation in average glucose utilization of the brain as a whole was observed. Highest levels of glucose utilization occurred during proestrus and metestrus, whereas lower rates were found during estrus and diestrus. Statistically significant fluctuations were found specifically in the hypothalamus and in some limbic structures. Rates of glucose utilization in the female rat brain were compared with rates in normal male rats. Statistically significant differences between males and females at any stage of the estrous cycle were confined mainly to hypothalamic areas known to be involved in the control of sexual behavior. Glucose utilization in males and females was not significantly different in most other cerebral structures.

Download Full-text

The Occurrence of Pain-Induced Depression Is Different between Rat Models of Inflammatory and Neuropathic Pain

Journal of Clinical Medicine ◽

10.3390/jcm10174016 ◽

2021 ◽

Vol 10 (17) ◽

pp. 4016

Author(s):

Yung-Chi Hsu ◽

Kuo-Hsing Ma ◽

Shu-Lin Guo ◽

Bo-Feng Lin ◽

Chien-Sung Tsai ◽

...

Keyword(s):

Neuropathic Pain ◽

Early Stage ◽

Preference Test ◽

Time Frame ◽

Brain Regions ◽

Rat Models ◽

Positron Emission ◽

Initial Injury ◽

Sucrose Preference Test ◽

The Brain

Various pain conditions may be associated with depressed mood. However, the effect of inflammatory or neuropathic pain on depression-like behavior and its associated time frame has not been well established in rat models. This frontward study investigated the differences in pain behavior, depression-like behavior, and serotonin transporter (SERT) distribution in the brain between rats subjected to spared nerve injury (SNI)-induced neuropathic pain or complete Freund’s adjuvant (CFA)-induced inflammatory pain. A dynamic plantar aesthesiometer and an acetone spray test were used to evaluate mechanical and cold allodynia responses, and depression-like behavior was examined using a forced swimming test and sucrose preference test. We also investigated SERT expression by using positron emission tomography. We found that the inflammation-induced pain was less severe than neuropathic pain from days 3 to 28 after induced pain; however, the CFA-injected rats exhibited more noticeable depression-like behavior and had significantly reduced SERT expression in the brain regions (thalamus and striatum) at an early stage (on days 14, 21, and 28 in two groups of CFA-injected rats versus day 28 in SNI rats). We speculated that not only the pain response after initial injury but also the subsequent neuroinflammation may have been the crucial factors influencing depression-like behavior in rats.

Download Full-text

Aging triggers an upregulation of a multitude of cytokines in the male and especially the female rodent hippocampus but more discrete changes in other brain regions

Journal of Neuroinflammation ◽

10.1186/s12974-021-02252-6 ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Latarsha Porcher ◽

Sophie Bruckmeier ◽

Steven D. Burbano ◽

Julie E. Finnell ◽

Nicole Gorny ◽

...

Keyword(s):

Statistical Tests ◽

Ventral Hippocampus ◽

Brain Regions ◽

Cytokine Expression ◽

Brown Norway ◽

Mouse Strains ◽

Gm Csf ◽

Age Related ◽

The Brain ◽

Related Increase

Abstract Background Despite widespread acceptance that neuroinflammation contributes to age-related cognitive decline, studies comparing protein expression of cytokines in the young versus old brains are surprisingly limited in terms of the number of cytokines and brain regions studied. Complicating matters, discrepancies abound—particularly for interleukin 6 (IL-6)—possibly due to differences in sex, species/strain, and/or the brain regions studied. Methods As such, we clarified how cytokine expression changes with age by using a Bioplex and Western blot to measure multiple cytokines across several brain regions of both sexes, using 2 mouse strains bred in-house as well as rats obtained from NIA. Parametric and nonparametric statistical tests were used as appropriate. Results In the ventral hippocampus of C57BL/6J mice, we found age-related increases in IL-1α, IL-1β, IL-2, IL-3, IL-4, IL-6, IL-9, IL-10, IL-12p40, IL-12p70, IL-13, IL-17, eotaxin, G-CSF, interfeuron δ, KC, MIP-1a, MIP-1b, rantes, and TNFα that are generally more pronounced in females, but no age-related change in IL-5, MCP-1, or GM-CSF. We also find aging is uniquely associated with the emergence of a module (a.k.a. network) of 11 strongly intercorrelated cytokines, as well as an age-related shift from glycosylated to unglycosylated isoforms of IL-10 and IL-1β in the ventral hippocampus. Interestingly, age-related increases in extra-hippocampal cytokine expression are more discreet, with the prefrontal cortex, striatum, and cerebellum of male and female C57BL/6J mice demonstrating robust age-related increase in IL-6 expression but not IL-1β. Importantly, we found this widespread age-related increase in IL-6 also occurs in BALB/cJ mice and Brown Norway rats, demonstrating conservation across species and rearing environments. Conclusions Thus, age-related increases in cytokines are more pronounced in the hippocampus compared to other brain regions and can be more pronounced in females versus males depending on the brain region, genetic background, and cytokine examined.

Download Full-text

Space-Dependent Glia–Neuron Interplay in the Hippocampus of Transgenic Models of β-Amyloid Deposition

International Journal of Molecular Sciences ◽

10.3390/ijms21249441 ◽

2020 ◽

Vol 21 (24) ◽

pp. 9441

Author(s):

Daniele Lana ◽

Filippo Ugolini ◽

Maria Grazia Giovannini

Keyword(s):

Brain Regions ◽

Therapeutic Strategies ◽

Differential Sensitivity ◽

Transgenic Models ◽

Age Related ◽

Neurodegenerative Pathology ◽

Spatial Differences ◽

Key Factor ◽

Β Amyloid ◽

The Brain

This review is focused on the description and discussion of the alterations of astrocytes and microglia interplay in models of Alzheimer’s disease (AD). AD is an age-related neurodegenerative pathology with a slowly progressive and irreversible decline of cognitive functions. One of AD’s histopathological hallmarks is the deposition of amyloid beta (Aβ) plaques in the brain. Long regarded as a non-specific, mere consequence of AD pathology, activation of microglia and astrocytes is now considered a key factor in both initiation and progression of the disease, and suppression of astrogliosis exacerbates neuropathology. Reactive astrocytes and microglia overexpress many cytokines, chemokines, and signaling molecules that activate or damage neighboring cells and their mutual interplay can result in virtuous/vicious cycles which differ in different brain regions. Heterogeneity of glia, either between or within a particular brain region, is likely to be relevant in healthy conditions and disease processes. Differential crosstalk between astrocytes and microglia in CA1 and CA3 areas of the hippocampus can be responsible for the differential sensitivity of the two areas to insults. Understanding the spatial differences and roles of glia will allow us to assess how these interactions can influence the state and progression of the disease, and will be critical for identifying therapeutic strategies.

Download Full-text

Astrocytes Couple Synaptic Activity to Glucose Utilization in the Brain

Physiology ◽

10.1152/physiologyonline.1999.14.5.177 ◽

1999 ◽

Vol 14 (5) ◽

pp. 177-182 ◽

Cited By ~ 15

Author(s):

Pierre J. Magistretti ◽

Luc Pellerin

Keyword(s):

Positron Emission Tomography ◽

Glucose Metabolism ◽

Glucose Utilization ◽

Glutamate Uptake ◽

Synaptic Cleft ◽

Synaptic Activity ◽

Emission Tomography ◽

Functional Characteristics ◽

Positron Emission ◽

The Brain

Astrocytes have functional characteristics that make them particularly well suited to couple glutamate uptake from the synaptic cleft to Na+-K+-ATPase activation and glucose utilization. The changes in glucose metabolism associated with these processes may provide signals detected by positron emission tomography.

Download Full-text

Regional Cerebral l-[14C-Methyl]Methionine Incorporation into Proteins: Evidence for Methionine Recycling in the Rat Brain

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.1992.84 ◽

1992 ◽

Vol 12 (4) ◽

pp. 603-612 ◽

Cited By ~ 20

Author(s):

Anna M. Planas ◽

Christian Prenant ◽

Bernard M. Mazoyer ◽

Dominique Comar ◽

Luigi Di Giamberardino

Keyword(s):

Rat Brain ◽

Specific Activity ◽

Plasma Source ◽

Brain Regions ◽

Emission Tomography ◽

Protein Breakdown ◽

Isotopic Equilibrium ◽

Positron Emission ◽

Time Periods ◽

The Brain

The specific activity (SA) of free methionine was measured in plasma and in different regions of the rat brain at 15, 30, or 60 min after intravenous infusion of l-[14C- methyl]methionine. Within these time periods, an apparent steady state of labeled free methionine in plasma and in brain was reached. However, the brain-to-plasma free methionine SA ratio was found to be ∼0.5, showing that an isotopic equilibrium between brain and plasma was not attained. This suggests the presence of an endogenous source of brain free methionine (likely originating from protein breakdown), in addition to the plasma source. The contribution of this endogenous source to the content of free methionine varies significantly among the different brain regions. Our results indicate that the regional rates of protein synthesis measured with l-[11C- methyl]methionine using positron emission tomography would be underestimated, since the local fraction of brain methionine derived from protein degradation would not be considered.

Download Full-text