Postmortem Stability of Monoamines, Their Metabolites, and Receptor Binding in Rat Brain Regibns

Kontur, Paul J.; Al-Tikriti, Mohammed S.; Innis, Robert B.; Roth, Robert H.

doi:10.1046/j.1471-4159.1994.62010282.x

Cited by 41 publications

(20 citation statements)

References 38 publications

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“…In rat brain, postmortem delay also leads to concentration changes of dopamine, norepinephrine, and serotonin in the occipital cortex. This effect, however, was not shared by all brain regions, as serotonin levels remained stable over an 18-h postmortem interval in the cingulate cortex (25). Furthermore, concentrations of many metabolites, such as myo-inositol, creatine, glutamine, glutamate, N-acetylaspartate, and taurine were shown to remain stable in the postmortem brain tissue over long time intervals (22,23,26,27).…”

Section: Freely Available Online Through the Pnas Open Access Optionmentioning

confidence: 92%

Rapid metabolic evolution in human prefrontal cortex

Giavalisco

Liu

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Human evolution is characterized by the rapid expansion of brain size and drastic increase in cognitive capabilities. It has long been suggested that these changes were accompanied by modifications of brain metabolism. Indeed, human-specific changes on gene expression or amino acid sequence were reported for a number of metabolic genes, but actual metabolite measurements in humans and apes have remained scarce. Here, we investigate concentrations of more than 100 metabolites in the prefrontal and cerebellar cortex in 49 humans, 11 chimpanzees, and 45 rhesus macaques of different ages using gas chromatography-mass spectrometry (GC-MS). We show that the brain metabolome undergoes substantial changes, both ontogenetically and evolutionarily: 88% of detected metabolites show significant concentration changes with age, whereas 77% of these metabolic changes differ significantly among species. Although overall metabolic divergence reflects phylogenetic relationships among species, we found a fourfold acceleration of metabolic changes in prefrontal cortex compared with cerebellum in the human lineage. These human-specific metabolic changes are paralleled by changes in expression patterns of the corresponding enzymes, and affect pathways involved in synaptic transmission, memory, and learning.H uman evolution is characterized by rapid expansion of brain size and increase in cognitive capabilities, leading to the emergence of unique and complex cognitive skills. These changes have long been associated with changes in brain metabolism, in particular with respect to increased energy demand (1). Large brains are metabolically costly. Thus, humans allocate approximately 20% of their total energy to the brain, compared with 11-13% for apes and 2-8% for other mammalian species (2). This increased metabolic demand has been associated with elevated expression of genes involved in neuronal functions and energy metabolism (3, 4). These changes may have been evolutionary advantageous, as indicated by signatures of positive selection reported for the amino acid changes, which occur in the mitochondrial electron-transport chain proteins, in anthropoid primates and humans, as well as elevated expression of the energy metabolism pathways in the human brain (5, 6). On the histological level, human brains show the largest density of glia cells relative to neurons in the prefrontal cortex, which provides an indirect indication of increased neuronal metabolic demand (7).Changes in brain metabolism are also implicated in neuropsychiatric disorders, such as schizophrenia, which affect some of the human-specific cognitive abilities (8, 9). Furthermore, direct measurements of 21 metabolites in the prefrontal cortex of adult human controls compared with human schizophrenia patients, chimpanzees, and rhesus macaques, carried out using proton NMR spectroscopy have shown significant overlap between human-specific evolutionary changes and metabolic differences between controls and schizophrenia patients (10). Notably, this study has identified not ...

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Section: Freely Available Online Through the Pnas Open Access Optionmentioning

confidence: 92%

Rapid metabolic evolution in human prefrontal cortex

Giavalisco

Liu

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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“…The available studies suggest that the function of the dopamine transporter, however, is not compromised (Naumann et al, 1998;Augood et al, 2002;Augood et al, 2004). It is worth bearing in mind that such biochemical studies are very difficult to conduct in humans because of the limited availability of suitable autopsy material, and because factors such as postmortem delay and differences in processing methods greatly influence biochemical and other measurements of dopamine metabolism (Spokes, 1979;Kontur et al, 1994;Hornykiewicz, 2001;Augood et al, 2004). Dopaminergic dysfunction has also been examined in several of the genetic animal models of DYT1 dystonia, using measurements of tissue levels of dopamine, and of its metabolites, 3,4-dihydroxy-phenylacetic acid (DOPAC) and homovanillic acid (HVA).…”

Section: Dopaminergic Dysfunction In Dyt1 Dystoniamentioning

confidence: 99%

Commentary: Dopaminergic dysfunction in DYT1 dystonia

Wichmann

2008

Experimental Neurology

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A three-base-pair deletion in the torsinA gene leads to generalized torsion dystonia (DYT1) in humans, an often devastating movement disorder in which voluntary movements are disrupted by sustained muscle spasms and abnormal limb posturing. In a recent issue of Experimental Neurology, Zhao et al. (2008) have provided a thorough behavioral, anatomic, and biochemical characterization of a mouse line that over-expresses human mutant torsinA, with particular emphasis on the possible role of dopaminergic dysfunction in these animals. This commentary provides an overview of the clinical and genetic features of the human disease and of the available transgenic mouse models for DYT1 dystonia, and discusses the evidence favoring the role of dopamine in the clinical manifestations of the disease.

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“…Indeed, the appearance of panic-like symptoms in Parkinsonian patients coincides with the time course of mesolimbic DA denervation (e.g., VTA and prefrontal cortex) [143][144][145]. In addition to alterations in mesolimbic DA activity, post-mortem analyses of Parkinsonian brain tissue have also provided evidence for altered nigrostriatal CCK activity [107][108][109][110]146]. Such changes in nigrostriatal CCK concentrations parallel indices of l-dopa treatment resistance (e.g., l-dopa resistant patients and animal model of Parkinson's disease [147][148][149][150][151] and symptom severity [107][108][109][110]).…”

Section: Central Dopamine Turnover: Prelude To Anxiety and Emergence mentioning

confidence: 98%

“…It is interesting that divergent alterations in DA associated with Parkinson's disease and schizophrenia are associated with the elicitation of panic-like symptoms. While mesocorticolimbic contribution to behavioral sensitization following stressor encounter [105,106] has received extensive Parkinson's disease is characterized by insidious nigrostriatal DA and CCK depletion [107][108][109][110][111][112]. In addition to tremor, inertia, rigidity, bradykinesia, akinesia, flexed posture and gait disturbance, Parkinsonian patients experience mild depression and irritability as well as memory and attentional perturbations [111,[113][114][115][116][117].…”

Section: Central Dopamine Turnover: Prelude To Anxiety and Emergence mentioning

confidence: 99%

“…In addition to alterations in mesolimbic DA activity, post-mortem analyses of Parkinsonian brain tissue have also provided evidence for altered nigrostriatal CCK activity [107][108][109][110]146]. Such changes in nigrostriatal CCK concentrations parallel indices of l-dopa treatment resistance (e.g., l-dopa resistant patients and animal model of Parkinson's disease [147][148][149][150][151] and symptom severity [107][108][109][110]). As such, it is conceivable that nigrostriatal DA/CCK and mesolimbic DA alterations contribute to the eventual expression of panic among Parkinsonian patients owing to the gradual denervation of mesocorticolimbic sites from the substantia nigra.…”

Section: Central Dopamine Turnover: Prelude To Anxiety and Emergence mentioning

confidence: 99%

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The Myth of Panic Spontaneity: Consideration of Behavioral and Neurochemical Sensitization

Hebb¹,

Anger²,

Mendella³

et al. 2007

TOPJ

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Panic disorder is characterized by a progression of panic symptom severity with repeated attacks. Repeated panic episodes evoke heightened anticipatory anxiety, phobic avoidance and are typically associated with comorbid symptoms of depression. Due to the heterogeneity of the disorder, reliable neurochemical correlates attending panic have not been identified. However, variable neuropeptide interfacing with major and minor transmitter systems may modulate individual vulnerability to panic and account for variable panic profiles. The extensive colocalization of cholecystokinin (CCK) with other neurotransmitters, including dopamine (DA), enkephalin (ENK) and GABA, in specific central sites may influence various aspects of anxiety and panic. The behavioral correlates attending panic likely follow from variable neurochemical release and conditioning/sensitization. Clinicians maintain that recurrent panic attacks are spontaneous (unexpected, uncued) and fail to acknowledge the wealth of information implicating a prominent role for stressful life events in panic. Conditioning and sensitization of both behavior (e.g., fear-motivated) and neurochemical events (e.g., DA and CCK) in response to uncontrollable stressors parallel the diverse heterogeneity of panic amongst clinical samples. Cholecystokinin-4, pentagastrin, lactate acid, and CO 2 induce panic attacks that are dependent on subjective history, expectancy measures and panic profiles. Panic disorder is associated with chronic illness and familial sick-role modeling exacerbates the course of the illness. The current review outlines the evidence in support of a conditioning/sensitization model for panic, a model that may explain the variable efficacies of pharmacological interventions.

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Postmortem Stability of Monoamines, Their Metabolites, and Receptor Binding in Rat Brain Regibns

Cited by 41 publications

References 38 publications

Rapid metabolic evolution in human prefrontal cortex

Rapid metabolic evolution in human prefrontal cortex

Commentary: Dopaminergic dysfunction in DYT1 dystonia

The Myth of Panic Spontaneity: Consideration of Behavioral and Neurochemical Sensitization

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