An fMRI study of personality influences on brain reactivity to emotional stimuli.

Functional imaging studies have examined which brain regions respond to emotional stimuli, but they have not determined how stable personality traits moderate such brain activation. Two personality traits, extraversion and neuroticism, are strongly associated with emotional experience and may thus moderate brain reactivity to emotional stimuli. The present study used functional magnetic resonance imaging to directly test whether individual differences in brain reactivity to emotional stimuli are correlated with extraversion and neuroticism in healthy women. Extraversion was correlated with brain reactivity to positive stimuli in localized brain regions, and neuroticism was correlated with brain reactivity to negative stimuli in localized brain regions. This study provides direct evidence that personality is associated with brain reactivity to emotional stimuli and identifies both common and distinct brain regions where such modulation takes place. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

5' Deiodinase activity in brain regions of adult rats: modifications in different situations of experimental hypothyroidism

In the central nervous system, type II 5' deiodinase (5'D-II) is highly regulated, as judged by the dramatic changes in enzyme levels observed after abrupt alterations in thyroid status. In this work, the 5'-DII activity has been studied in different situations of experimental hypothyroidism (propylthiouracil, methimazole, thyroidectomy, and low iodine diet), in various brain regions (pituitary, cerebellum, brain stem, hypothalamus, cortex, and whole brain) in adult rats. Propylthiouracil and methimazole significantly increase the activity in all brain regions. These increases are higher in rats treated with methimazole. Thyroidectomy significantly increases the activity in cortex and pituitary. A low iodine diet significantly increases in all brain regions except in the hypothalamus. The concentration of triiodothyronine (T3) studied in the major brain regions remained unchanged. The results obtained show a compensatory mechanism in pituitary and other brain regions in order to maintain the T3 levels in brain tissue.     

Neural Substrates of Coping Behavior in the Rat: Possible Importance of Mesocorticolimbic Dopamine System.

This study measured expression of Fos protein, an indicator of neural activation, in 116 brain regions of rats that were able to control a stressor (i.e., avoid and/or escape an electric shock), and compared the changes with those observed in yoked rats that received the same shocks but without having control over them. The authors' interest was to find brain regions where elevated activity occurs in conjunction with control. Activity in these brain regions might be responsible for the consequences of having control, such as reduction of stress responses. Eleven brain regions were found in which rats with control showed significantly more Fos expression than was seen in yoked rats that did not have control. Six of these brain regions were part of the mesocorticolimbic dopamine system. These results point to the mesocorticolimbic dopamine system as being importantly involved in the mediation and/or the consequences of coping behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of manganese on the levels of DNA, RNA, DNase and RNase in cerebrum, cerebellum and rest of brain regions of rat

Levles of DNA, RNA, DNase, RNase and manganese in different regions of rat brain were studied after daily administration of manganese chloride (8 mg MnCl2-4H2O/kg intraperitoneally) for a period of 120 days. DNA and RNA contents decreased significantly in cerebrum, cerebellum and rest of the brain regions after manganese treatment. A decrease in the DNase and an increase in the RNase activity was observed in the cerebellum and rest of brain region of the manganese treated animals. The manganese content increased significantly in all the regions of the brain, the maximum concentration being in the rest of brain portion. The presence of excess manganese in brain presumably leads to alterations in the functional activity of lysosomal enzymes. The decrease in the levels of nucleic acids is perhaps a consequence of the degenerating and dead neurones.     

The neurochemical set of the brain--an extra-immune mechanism of psychoneuroimmunomodulation

The present study provides evidence for involvement of brain neurotransmitters in the control of an immune response. The extra-immune mechanism of immunomodulation is considered by analyzing drug-induced changes in the brain neurotransmitter systems, brain destruction, altered activity of brain regions due to psychoemotional stress, including mental disease. It is suggested that the pattern of neurotransmitter activity with its prevalence in certain brain regions determines the neurochemical set-up of the brain for psychoneuroimmunomodulation, i.e. its extra-immune mechanism.     

Influence of ethanol on cadmium accumulation and its impact on lipid peroxidation and membrane bound functional enzymes (Na+, K(+)-ATPase and acetylcholinesterase) in various regions of adult rat brain

Influence of ethanol on cadmium accumulation and its effect on metallothionein induction, binding of cadmium to metallothionein, lipid peroxidation and membrane bound functional enzymes such as (Na(+)-K+)-ATPase and acetylcholinesterase in various regions of adult rat brain was investigated. Ethanol (2 g/kg body wt) and cadmium (1 mg/kg body wt) were administered alone as well as in combination to different groups of rats, i.p., for a period of 1 week. It was observed that cadmium when co-administered with ethanol led to pronounced increase in cadmium accumulation in various regions of the brain. This ethanol induced accumulation of cadmium did not induce the synthesis of metallothionein and also did not bind to this protein in brain and mainly was present as non-metallothionein bound cadmium. It lead to a significant increase in lipid peroxidation and inhibition of membrane bound functional enzymes; (Na(+)-K+)-ATPase and acetylcholinesterase in various regions of the brain indicating functional impairment. The results of the present study imply that ethanol renders the adult brain more susceptible to cadmium neurotoxicity. Corpus striatum and cerebral cortex are more vulnerable regions than other areas of the brain.     

Larry R. Squire.

Larry R. Squire receives an award for his seminal and decisive studies on the brain substrates of declarative memory in humans and monkeys. His work is virtually unique in that he identified regions of the brain that appeared critical for anterograde amnesia in humans with brain damage and analyzed the roles of these brain regions in elegant experimental studies in monkeys. This article contains a citation and a biography of Larry R. Squire. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Low body weight in Alzheimer's disease is associated with mesial temporal cortex atrophy

There are reports of weight loss and low body mass index (BMI) in patients with AD. The mesial temporal cortex (MTC) is involved in feeding behavior and memory and is preferentially involved in AD. We studied 74 subjects, including 58 AD patients and 16 control subjects, to determine whether BMI is associated with atrophy of the MTC or other brain regions. We used MRI morphometric analysis to provide measures of regional brain atrophy. AD patients had significant brain atrophy in all measured brain regions, except the white matter, compared with normal control subjects. The MTC was the only brain region significantly associated with BMI in AD patients (r = 0.39, p = 0.003). Multiple-regression analysis indicated that addition of brain regions other than the MTC to the model did not significantly add to the prediction of BMI. We conclude that low BMI correlates best and specifically with MTC atrophy. This finding supports a connection between limbic system damage and low body weight in AD.     

Immobilization of collared peccaries (Tayassu tajacu) and feral hogs (Sus scrofa) with Telazol and xylazine

Quantitative [125I]protein G-based immunohistochemistry was used to map the distribution of beta1 thyroid hormone receptor (TRbeta1) in normal and thyroidectomized adult rat brain, using a previously characterized polyclonal antibody. The distribution of TRbeta1-like immunoreactivity in normal brain was largely but not perfectly concordant with previous accounts of TRbeta1 mRNA distribution in rat brain. Thyroidectomy resulted in increased immunolabeling in most brain regions (mean increase: 14%, range: -4% to +25%), with statistically significant effects being observed in 9 of the 36 brain regions examined. Brain regions showing the most pronounced effects included the habenular nucleus (+22%), the oriens layer of the hippocampal CA3 region (+24%), and the lateral geniculate nucleus of the thalamus (+23%). These results demonstrate that the TRbeta1 protein in brain is capable of plastic changes in response to adult-onset alterations in TH levels. The observed pattern of brain regional receptor changes following thyroidectomy may provide clues for functional effects of thyroid function alterations in adults.     

Creatine kinase-B mRNA levels in brain regions from male and female rats

The creatine kinase-B (CKB) enzyme is proposed to have a pivotal role in the regeneration of ATP in the nervous system. In the present study, the steady-state levels of CKB mRNA were determined by RNase protection assay in seventeen separate brain regions obtained from rats during the initial interval of the light period or period of inactivity in rats. The antisense probe used specifically hybridizes to CKB mRNA and discriminates CKB from CKM mRNA. The results show that brain regions from Wistar rats differ in CKB mRNA content. Highest levels of CKB mRNA were detected in the male and female cerebellum. High levels of CKB mRNA were observed in the spinal cord, brain stem and its structures (medulla, pons and midbrain) and olfactory bulb of the male rats. Female rats also contained high levels of CKB mRNA in the brain stem. In both male and female rats, the frontal cortex, occipital cortex, hippocampus and striatum exhibited lower levels of CKB mRNA relative to the complete brain. Statistical analyses demonstrated a significant difference between the male and female CKB mRNA profiles. However, CKB mRNA levels in brain regions with estrogen receptors (hypothalamus, hippocampus) were similar in male and female rats. Differential CKB mRNA levels in various brain regions may suggest diverse physiological significance of the CKB system in the regulation of brain energy metabolism.     

The uniquely distributed isoprenylated protein methyltransferase activity in the rat brain is highly expressed in the cerebellum

Isoprenylated protein methyltransferase, the enzyme which catalyzes the reversible methylation of signal transducing G-proteins was studied in nine brain regions of the rat brain using S-farnesyl cysteine analogs as substrates. Enzyme activity, as determined with N-acetyl-S-farnesyl-L-cysteine (AFC) was found in the nuclear, synaptosomal and microsomal fractions of all brain regions but not in the cytosol. The enzyme is a unique methyltransferase with respect to its brain distribution. The rank order of activity of the enzyme is cerebellum > midbrain > medulla > forebrain regions, where activities in cerebellar synaptosomal and nuclear fractions (28-32 pmol AFC [methyl-3H]ester formed/min/mg prot) are 20 to 30 times higher than those of the corresponding fraction of the forebrain regions. This distribution is reminiscent of that of neurotransmitter receptors and signal transduction molecules and suggests a regulatory role for the enzyme, particularly in the cerebellum.     

Changes in the central and peripheral serotonergic system in rats exposed to water-immersion restrained stress and nicotine administration

The effects of water-immersion restraint stress (WS) on chronically nicotine-administered rats were studied in the blood and various regions of the brain. Serotonin (5-HT) levels increased in the hypothalamus, hippocampus, cortex and cerebellum following the administration of nicotine. 5-HT levels increased in all the brain regions following stress. Nicotine decreased stress-induced increased levels of 5-HT in the hippocampus and cerebellum. Nicotine administration alone increased 5-hydroxyindole acetic acid (5-HIAA) levels in the hippocampus and cerebellum. Stress alone also increased 5-HIAA levels in all the brain regions. In the cortex, 5-HT and 5-HIAA levels further increased following the administration of a combination of stress and nicotine compared to rats given stress alone. In the blood as well as in all the brain regions, except the cerebellum, stress or nicotine administration did not affect tryptophan levels. Stress given to nicotine-administered rats resulted in a decrease in tryptophan levels in the blood and plasma. Although 5-HT and 5-HIAA levels were not influenced by stress and/or nicotine administration, the 5-HIAA/5-HT ratio increased in the blood and plasma of rats administered with nicotine and exposed to stress. The effects of nicotine on the serotonergic system depend upon the kind of stress given together with the organs and brain regions involved.     

Expression and region-specific regulation of the oxytocin receptor gene in rat brain

The neuropeptide oxytocin (OT) exerts its various neurotransmitter functions via specific OT receptors (OTRs) that have been localized to distinct brain regions, including the ventromedial hypothalamus, the bed nucleus of stria terminalis, the amygdala, the subiculum, the hippocampus, and the olfactory nuclei. In the present study, we have characterized OTR gene expression by Northern blot and by semiquantitative RT-PCR in these brain regions and studied its regulation in response to estrogen (E2), progesterone, and the antiestrogen tamoxifen. We find that all regions analyzed express two messenger RNA (mRNA) bands (6.7 and 4.8 kb) that hybridize to a rat OTR complementary DNA probe and that correspond in size to two of the three OTR mRNA bands expressed in rat uterus. Analysis by RT-PCR, with two different primer pairs, did not reveal any structural differences between the coding regions of uterine and brain OTR mRNA. E2 treatment and gestation led to an 8-fold and a 6.5-fold increase in OTR mRNA levels, respectively. Progesterone was without effect, if administered alone, and did not influence the E2-induced rise in OTR mRNA. The E2 effect was restricted to E2-sensitive regions, such as the hypothalamus, and was not observed in the subiculum or the olfactory nuclei. Tamoxifen had a dual effect: on the one hand, it acted as a partial agonist in raising OTR mRNA levels in the hypothalamus of ovariectomized animals; on the other hand, it suppressed the E2-induced OTR mRNA rise in E2-sensitive brain regions. Although the present data do not exclude the possible existence of OTR subtype(s) in brain, they show that the uterine-type OTR gene is expressed in all major OTR-containing brain regions. Moreover, they show that region-specific regulation of OTR gene expression underlies the previously observed region-specific steroid regulation of central OT binding sites.     

Epidemiological study of myasthenia gravis in the province of Reggio Emilia, Italy

In vitro binding profiles were determined for selected benzodiazepine receptor (BZR) ligands by quantitative radioautography in rat brain. The ligands represent subtype-selective agonists (zolpidem) or nonselective BZR agonists (diazepam), as well as BZR partial agonists (bretazenil, Ro 43-9624, and Ro 19-8022). In addition, these compounds were evaluated in a precipitated withdrawal paradigm in monkeys. The physical dependence liability was not clearly related to the in vitro brain BZR binding profiles of these compounds. Therefore, diazepam, bretazenil, Ro 19-8022, and Ro 43-9624 had regional affinities for the 13 selected rat brain regions that were close to the mean values across regions, despite the clearly greater physical dependence potential of diazepam. Zolpidem, on the other hand, had regional affinities for the 13 rat brain regions that diverged significantly from the mean value across regions and exhibited a lower physical dependence potential than diazepam. These results raise the possibility that a combination of BZR subtype selectivity with partial agonism could yield a marked reduction of physical dependence liability.     

Induction of interleukin-1 in various brain regions after peripheral and central injections of lipopolysaccharide

The presence of bioactive interleukin-1 (IL-1) in various brain regions (cerebellum, cortex, brainstem, diencephalon or hippocampus) after either intraperitoneal (i.p.) or intraventricular (i.c.v.) injection of lipopolysaccharide (LPS) was studied in the rat. To detect IL-1, extracellular fluid and cell lysate were fractionated by gel exclusion chromatography and fractions tested for thymocyte stimulation; presence of IL-1 was confirmed by blockade of stimulation by addition to the assay of a monoclonal antibody (mAb) to IL-1 receptor. When LPS was infused i.c.v., IL-1 was detected in the brainstem and diencephalon 2 h after injection, and in all the brain regions except cerebellum 6 h after injection; IL-1 was not detected in the plasma of these animals. When LPS was injected i.p., IL-1 was detected in the plasma but not in the brain 2 h after the injection, and in all brain regions but not in the plasma 6 h after the injection. In all of these cases, IL-1 was found in extracellular fluid; in some cases (cortex, cerebellum) cell lysate of the region did not produce detectable bioactivity, thereby indicating that IL-1 in these brain regions is processed to active peptide during release, as has been reported in the periphery. In those cases where bioactivity was detected in cell lysate (brainstem, diencephalon), bioactivity was not blocked by IL-1 receptor mAb, indicating presence of a non-IL-1 stimulating factor. These results further support the idea that IL-1 is secreted by cells in the brain, and indicate that it is found in the extracellular fluid of many brain regions following an appropriate stimulus in the periphery as well as in the brain.     

Dysfunctions in multiple interrelated systems as the neurobiological bases of schizophrenic symptom clusters

The absence of an animal model that accurately approximates schizophrenia limits current research into the pathophysiology of this disorder. Obviously, the cognitive disturbances associated with schizophrenia are difficult to evaluate in laboratory animals. Nonetheless, animal studies have provided insight into the anatomy and physiology of the brain systems that have been implicated in schizophrenia. These studies also suggest how brain systems may be involved in information processing in normal and pathological conditions. Thus, a careful assessment of the properties and functions of the brain regions suggested to be involved in schizophrenic symptoms has been a primary objective in several laboratories. In this review, we discuss the interactions among the brain regions implicated in schizophrenia--the ventral striatum, prefrontal cortex, hippocampus, and dopamine systems--and provide an integrative model linking altered function in these regions with specific clusters of symptoms of schizophrenia.     

Thiamine triphosphate levels and histopathology. Correlation in Leigh disease

Thiamine and thiamine triphosphate (TTP) values were assayed in various brain regions in 11 controls and 13 patients with subacute necrotizing encephalomyelopathy (SNE, Leigh disease). The TTP values of normal brain were 5% of the total thiamine value. The relative TTP (or % TTP) level was consistently low in the pons, midbrain, and cerebellum of all the SNE brains. Twenty-five percent of the SNE brains had normal TTP levels in the frontal region. The TTP values correlated with the degrees of pathologic involvement in all sampled regions of the brain except the cerebellum. The concentration of thiamine in the mammillary bodies exceeded its concentration elsewhere in both control and SNE brains. The finding of low TTP levels in morphologically abnormal regions supports the hypothesis that TTP deficiency is etiologically related to SNE.     

Abundance of cyclo (His-Pro)-like immunoreactivity in the brain of TRH-deficient mice

Cyclo(His-Pro) or CHP was initially discovered as a metabolite of thyrotropin-releasing hormone (TRH) resulting from the action of the enzyme Pyroglutamyl aminopeptidase. Physiologic and pharmacologic studies that followed this initial discovery provided indirect evidence that all CHP may not be derived from TRH. However, the recent availability of a TRH-deficient mouse has made it possible to reinvestigate whether CHP is derived from TRH. In the present study, we examined distribution of CHP and TRH in TRH-deficient mice. Northern blot analysis confirmed the absence of preproTRH mRNA in both the hypothalamus and the cortex of TRH-deficient mice. Brains from the wild-type and TRH-deficient mice were dissected into 7 regions, and TRH and CHP concentrations were determined by specific radioimmunoassay (RIA) in each region. Whereas TRH was identified in all regions of the wild-type brain, with the highest concentration in the hypothalamus, no detectable TRH was observed in any region in the TRH-deficient mice. While CHP-like immunoreactivity (CHP-LI) was present in all regions in the wild-type brain, its concentration was reduced by approximately 50% in the hypothalamus and cerebral cortex of TRH-deficient mice, with no change in other brain regions. Furthermore, the CHP-LI present in the brain of TRH-deficient mice was immunologically and chromatographically identical to synthetic CHP. These findings strongly suggest that a portion of the CHP in the brain is derived from sources other than TRH.     

Electrochemical analysis of protein nitrotyrosine and dityrosine in the Alzheimer brain indicates region-specific accumulation

HPLC with electrochemical array detection (HPLC-ECD) was used to quantify 3,3'-dityrosine (diTyr) and 3-nitrotyrosine (3-NO2-Tyr) in four regions of the human brain that are differentially affected in Alzheimer's disease (AD). DiTyr and 3-NO2-Tyr levels were elevated consistently in the hippocampus and neocortical regions of the AD brain and in ventricular cerebrospinal fluid (VF), reaching quantities five- to eightfold greater than mean concentrations in brain and VF of cognitively normal subjects. Uric acid, a proposed peroxynitrite scavenger, was decreased globally in the AD brain and VF. The results suggest that AD pathogenesis may involve the activation of oxidant-producing inflammatory enzyme systems, including nitric oxide synthase.     

The functional anatomy of memory

A review of recent work using Positron Emission Tomography (PET) to examine brain systems involved in auditory-verbal memory is presented. Initial work delineated widespread brain regions which were, to a large extent, in agreement with existing neuropsychological literature. Expanding on this, a number of studies have examined memory encoding and retrieval separately. Additionally, experiments have been carried out to specifically address sub-components of memory such as the use of visual imagery as a mnemonic strategy, the functional anatomical evidence for the episodic/semantic memory distinction and the different brain regions involved in explicit and implicit memory tasks.