Regions Of Cerebral Cortex Research Articles

MiRNA expression analysis in cortical dysplasia: Regulation of mTOR and LIS1 pathway

Cortical dysplasia (CD) is a common cause of epilepsy in children and is characterized by focal regions of malformed cerebral cortex. The pathogenesis and epileptogenesis of CD have not been fully elucidated, and in particular, the potential role of epigenetics has not been examined. miRNA microarray was performed on surgical specimens from CD (n=8) and normal control (n=2) children. A total of 10 differentially expressed miRNAs (DEmiRs) that were up-regulated in CD were identified including hsa-miR-21 and hsa-miR-155. The microarray results were validated using quantitative real-time PCR. After searching for the putative target genes of the DEmiRs, their biological significance was further evaluated by exploring the pathways in which the genes were enriched. The mammalian target of rapamycin (mTOR) signaling pathway was the most significantly associated, and the pathway of lissencephaly gene in neuronal migration and development was also noted. This study suggests a possible role for miRNAs in the pathogenesis of CD, especially in relation to the mTOR signaling pathway. Future studies on the epigenetic mechanisms underlying CD pathogenesis and epileptogenesis are needed.

Spike firing and IPSPs in layer V pyramidal neurons during beta oscillations in rat primary motor cortex (M1) in vitro.

Beta frequency oscillations (10–35 Hz) in motor regions of cerebral cortex play an important role in stabilising and suppressing unwanted movements, and become intensified during the pathological akinesia of Parkinson's Disease. We have used a cortical slice preparation of rat brain, combined with concurrent intracellular and field recordings from the primary motor cortex (M1), to explore the cellular basis of the persistent beta frequency (27–30 Hz) oscillations manifest in local field potentials (LFP) in layers II and V of M1 produced by continuous perfusion of kainic acid (100 nM) and carbachol (5 µM). Spontaneous depolarizing GABA-ergic IPSPs in layer V cells, intracellularly dialyzed with KCl and IEM1460 (to block glutamatergic EPSCs), were recorded at −80 mV. IPSPs showed a highly significant (P< 0.01) beta frequency component, which was highly significantly coherent with both the Layer II and V LFP oscillation (which were in antiphase to each other). Both IPSPs and the LFP beta oscillations were abolished by the GABAA antagonist bicuculline. Layer V cells at rest fired spontaneous action potentials at sub-beta frequencies (mean of 7.1+1.2 Hz; n = 27) which were phase-locked to the layer V LFP beta oscillation, preceding the peak of the LFP beta oscillation by some 20 ms. We propose that M1 beta oscillations, in common with other oscillations in other brain regions, can arise from synchronous hyperpolarization of pyramidal cells driven by synaptic inputs from a GABA-ergic interneuronal network (or networks) entrained by recurrent excitation derived from pyramidal cells. This mechanism plays an important role in both the physiology and pathophysiology of control of voluntary movement generation.

Diffusion tensor imaging of spinocerebellar ataxia type 12.

BackgroundSpinocerebellar ataxias (SCAs) are autosomal-dominant neurodegenerative diseases that are clinically and genetically heterogeneous. SCAs are characterized by a range of neurological symptoms. SCA12 is an autosomal-dominant (AD) ataxia caused by a CAG repeat expansion mutation in a presumed promoter region of the gene PPP2R2B in a non-coding region on chromosome 5q32. This study sought to determine changes in different positions in a single Uyghur SCA12 pedigree by measuring the apparent diffusion coefficient (ADC) and fractional anisotropy (FA).Material/MethodsA single Uyghur pedigree was collected and was confirmed to possess SCA12 by genetic diagnosis, among which 13 cases were patients and 54 cases were “healthy” individuals. Five patients were presymptomatic and 15 individuals selected as a control group were examination in the same time. DTI was performed on a 1.5T scanner, with b=1000 s/mm2 and 15 directions. ADC and FA were measured by regions of interest positioned in the corticospinal tract at the level of the pons (pons), superior peduncle (SCP), middle cerebellar peduncle (MCP), cerebellar cortex (CeC), cerebral cortex (CC), and cerebellar vermis (CV) white matter.ResultsCompared with the controls, the ADC was significantly elevated in the CeC, SCP, CC, and CV regions in SCA12 patients. The FA significantly decreased in the CC region in SCA12 patients and the CC and CV regions in SCA12 presymptomatic patients. The course of the disease, SARA score, and ADC values in CV showed highly positive correlations.ConclusionsSCA12 pedigree patients exhibited microstructural damage in the brain white matter. The damage in white matter fiber may first occur in the CC and CV regions in SCA12 presymptomatic patients. The ADC values in the CV region could reflect disease severity in SCA12 patients.

A brief review on studies of Alzheimer’s disease in China: Its mechanism, imaging and therapy

Alzheimer’s disease (AD) was first described by German psychiatrist and neuropathologist Alois Alzheimer in 1906 and was named after him. It is the most common form of dementia and highly prevalent. AD is predicted to affect one in 85 people globally by 2050. Well-known examples include Ronald Reagan, former US President, and Charles K. Kao, recipient of the 2009 Nobel Prize in Physics. The neuropathology of AD is characterized by loss of neurons and synapses in cerebral cortex and certain subcortical regions. Both amyloid plaques and neurofibrillary tangles are clearly visible by microscopy in brains of those afflicted by AD. However, the cause for most Alzheimer’s cases remains essentially unknown, except for 1%–5% of cases where genetic differences have been identified. Several competing hypotheses exist, trying to explain the cause of this disease, such as cholinergic hypothesis, amyloid hypothesis, and Tau hypothesis.

Quercetin suppress microglial neuroinflammatory response and induce antidepressent-like effect in olfactory bulbectomized rats

In rodents, olfactory bulbectomy (OBX) results in several behavioral and biochemical changes, useful as a screening model for antidepressants. Recent evidences suggest that quercetin; a bioflavonoid exhibits a variety of behavioral effects including anxiolytic, antidepressant, etc. Since microglia are commonly implicated in the neuroinflammation cascade of depression, we hypothesized that quercetin might involve microglial inhibition pathway in its antidepressant-like effects. To support such a possibility, we investigated the interaction of quercetin with a known microglial inhibitor (minocycline) against OBX-induced depression in male Wistar rats. In our study, ablation of olfactory bulbs caused hyperactivity in open field arena and increased immobility time in forced swim test (FST) which was coupled with enhanced serum corticosterone levels. Additionally, there were increased oxidative–nitrosative stress markers, inflammatory mediators (tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)) along with enhanced apoptotic factor (caspase-3) in both cerebral cortex and hippocampal brain regions of OBX animals. These results were further supported by reports from histopathological analysis. After a surgical recovery period of 2weeks, treatment with quercetin (40, 80mg/kg; per oral (p.o.) p.o., 14days) significantly prevented OBX-induced behavioral, biochemical, molecular and histopathological alterations. Further, combination of sub effective doses of quercetin (20, 40mg/kg; p.o.) with minocycline (25mg/kg; p.o.) significantly potentiated their protective effects as compared to their effects alone. Based on our results, we propose that microglial inhibitory pathway might be involved in the neuroprotective effects of quercetin and suppression of oxidative–nitrosative stress mediated neuroinflammation-apoptotic cascade associated with OBX rat model of depression.

Comparative lipidomics of mouse brain exposed to enriched environment

Several studies have shown that housing conditions and environmental exposure to a series of stimuli lead to behavior improvement in several species. While more works have been focused on illustrating changes of the proteome and transcriptome following enriched environment exposure in mice, little has been done to understand changes in the brain metabolome in this paradigm due to the complexity of this type of analysis. In this paper, lipidomics focused on phospholipids and gangliosides were conducted for brain tissues of mice exposed to enriched or impoverished conditions. We optimized previously reported method and established a reliable relative comparison method for phospholipids and gangliosides in brain tissue using prefractionation with weak anion exchange cartridge. We used liquid chromatography mass spectrometry to explore metabolic signatures of the cerebral cortex and hippocampus after confirming the animals had significant memory differences using the fear conditioning paradigm and brain immunohistochemistry. Although both cerebral cortex and hippocampus regions did not show major alterations in ganglioside composition, we found significant differences in a series of phospholipids containing 22:6 fatty acid in the prefrontal cortex, indicating that environmental enrichment and impoverished housing conditions might be a relevant paradigm to study aberrant lipid metabolism of docosahexaenoic acid consumption. Our study highlights the hypothesis-generating potential of lipidomics and identifies novel region-specific lipid changes possibly linked not only to change of memory function in these models, but also to help us better understand how lipid changes may contribute to memory disorders.

Anti-oxidant, anti-inflammatory and anti-cholinergic action of Adhatoda vasica Nees contributes to amelioration of diabetic encephalopathy in rats: Behavioral and biochemical evidences

‘Diabetic encephalopathy’ refers to diabetes associated cognitive decline (DACD), which involves oxidative-nitrosative stress, inflammation and cholinergic dysfunction. Current study was designed to investigate the effect of Adhatoda vasica, a known anti-inflammatory, antioxidant, anti-cholinesterase and anti-hyperglycemic plant, on diabetic encephalopathy. Streptozotocin (STZ)-induced diabetic Wistar rats were treated with Adhatoda vasica leaves ethanolic extract (AVEE) for 6 weeks at 100, 200 and 400 mg/kg/day dose. During fifth week of treatment, learning and memory was investigated in single Y-maze and passive avoidance test. At the end of the study biochemical parameters like acetylcholinesterase (AchE) activity, nitrite levels, tumor necrosis factor-alpha (TNF-α) and oxidative stress was measured from cerebral cortex and hippocampus regions of brain. AchE activity was found increased by 70 % in the cerebral cortex of diabetic rat brain. Lipid peroxidation (LPO) levels were increased by 100 % and 94 % in cerebral cortex and hippocampus of diabetic rats, respectively. Non-protein thiol levels, enzymatic activities of superoxide dismutase and catalase were found decreased in cerebral cortex and hippocampal regions of diabetic rat brain. Nitrite levels in both regions of diabetic brain were increased by 170 % and 137 % respectively. TNF-α, a pro-inflammatory cytokine, was found significantly increased in diabetic rats. Conversely, animal groups treated with AVEE significantly attenuated these behavioral and biochemical abnormalities. The results suggest a protective role of Adhatoda vasica Nees against diabetic encephalopathy, which may be sum of its anti-oxidant, anti-cholinesterase, anti-inflammatory and glucose lowering action.

Ferulic acid attenuates focal cerebral ischemia-induced decreases in p70S6 kinase and S6 phosphorylation

Ferulic acid exhibits neuroprotective effects against focal cerebral ischemia. PI3/K and Akt signaling pathways play an essential role in protecting against cerebral ischemia. Mammalian target of rapamycin (mTOR), a major downstream target of Akt, regulates p70S6 kinase and S6, both of which are involved in ribosomal biogenesis and protein synthesis. I investigated whether ferulic acid regulates mTOR, p70S6 kinase, and S6 phosphorylation during brain ischemic injury. Rats were treated immediately with vehicle or ferulic acid (100mg/kg, i.v.) after middle cerebral artery occlusion (MCAO). Brains tissues were removed at 24h after the onset of MCAO and the cerebral cortex regions were collected. Ferulic acid reduced the MCAO-induced infarct volume. I showed previously that ferulic acid prevents the MCAO injury-induced decrease of Akt phosphorylation. In this study, MCAO injury induced decreases in mTOR, p70S6 kinase, and S6 phosphorylation levels, while ferulic acid attenuated the injury-induced decreases. Immunohistochemical staining demonstrated that ferulic acid prevented the MCAO-induced reduction in the number of positive cells for phosphorylated p70S6 kinase and phosphorylated S6. These findings suggest that ferulic acid has a neuroprotective function against focal cerebral ischemia by modulating p70S6 kinase expression and S6 phosphorylation.

Functional Genomics Reveals Dysregulation of Cortical Olfactory Receptors in Parkinson Disease: Novel Putative Chemoreceptors in the Human Brain

Parkinson disease (PD) is no longer considered a complex motor disorder but rather a systemic disease with variable nonmotor deficits that may include impaired olfaction, depression, mood and sleep disorders, and altered cortical function. Increasing evidence indicates that multiple metabolic defects occur in regions outside the substantia nigra, including the cerebral cortex, even at premotor stages of the disease. We investigated changes in gene expression in the frontal cortex in PD patient brains using a transcriptomics approach. Functional genomics analysis indicated that cortical olfactory receptors (ORs) and taste receptors (TASRs) are altered in PD patients. Olfactory receptors OR2L13, OR1E1, OR2J3, OR52L1, and OR11H1 and taste receptors TAS2R5 and TAS2R50 were downregulated, but TAS2R10 and TAS2R13 were upregulated at premotor and parkinsonian stages in the frontal cortex area 8 in PD patient brains. Furthermore, we present novel evidence that, in addition to the ORs, obligate downstream components of OR function adenylyl cyclase 3 and olfactory G protein (Gαolf), OR transporters, receptor transporter proteins 1 and 2 and receptor expression enhancing protein 1, and OR xenobiotic removing UDP-glucuronosyltransferase 1 family polypeptide A6 are widely expressed in neurons of the cerebral cortex and other regions of the adult human brain. Together, these findings support the concept that ORs and TASRs in the cerebral cortex may have novel physiologic functions that are affected in PD patients.

Kainic acid induces expression of caveolin-1 in activated microglia in rat brain

Caveolin-1, a major constituent of caveolae, has been implicated in endocytosis, signal transduction and cholesterol transport in a wide variety of cells. In the present study, the expression of caveolin-1 was examined by immunohistochemistry in rat brain with or without systemic injection of kainic acid (KA). Caveolin-1 immunoreactivity was observed in capillary walls in brains of control rats. From one to seven days after KA injection, caveolin-1 immunoreactivity appeared in activated microglia in the cerebral cortex, hippocampus and other brain regions. The strongest immunoreactivity of microglia was seen after 3 days after KA administration. The expression of caveolin-1 was confirmed by RT-PCR and Western blot analysis, respectively. The induction of caveolin-1 expression in microglia activated in response to kainic acid administration suggests its possible role in a modulation of inflammation.

Baicalein이 Lipopolysaccharide에 의한 생쥐의 Neuroinflammation에 미치는 영향

Objects : Baicalein is a major bioactive flavonoid component of Scutellaria baicalensis Georgi that shows a wide range of biological activities, including neuroprotections and anti-inflammatory actions. Hence it is a potential therapeutic material for the treatment of neuroinflammation. In this study, we investigated the modulatory effect of baicalein on neuroinflammation. Method : Pro-inflammatory cytokines (TNF-<TEX>${\alpha}$</TEX>, IL-<TEX>$1{\beta}$</TEX> and IL-6 mRNA), COX-2 mRNA expression and microglial activation in the brain tissue is induced by systemic lipopolysaccharide (LPS) treatment in C57BL/6 mice. Baicalein was treated orally with 10, 20, and 30 mg/kg 1 hour prior to the LPS (3 mg/kg, i.p.) injection. TNF-<TEX>${\alpha}$</TEX>, IL-<TEX>$1{\beta}$</TEX>, IL-6 and COX-2 mRNA expression in the brain tissue was measured by the quantitative real-time polymerase chain reaction(PCR) method. Iba1 expression in the brain was measured by western blotting method. Microglia was observed with immunohistochemistry. Results : Baicalein 30 mg/kg significantly attenuated the expression of TNF-<TEX>${\alpha}$</TEX>, IL-<TEX>$1{\beta}$</TEX>, IL-6 and COX-2 mRNA in the brain tissue. Baicalein 20 mg/kg significantly attenuated the expression of IL-6 mRNA in the brain tissue. Baicalein 30 mg/kg significantly attenuated the expression of Iba1 protein expression in the brain tissue. Baicalein 30 mg/kg significantly decreased the number and cell size of microglia in the cerebral cortex and hypothalamic region and the area percentage of Iba1-expressed microglia in the hippocampus. Conclusion : These results demonstrated that baicalein attenuates LPS induced neuroinflammation in the mice via reduction of pro-inflammatory cytokines (TNF-<TEX>${\alpha}$</TEX>, IL-<TEX>$1{\beta}$</TEX>, IL-6), COX-2 mRNA expression and microglial activation.

P.1.014 Intracerebroventricular administration of interleukin-1β elevates brain kynurenic acid and disrupts prepulse inhibition in C57BL/6 mice

Olfactory bulbectomy (OBX) is a well known screening model for depression. Panax quinquefolium (PQ) is known for its therapeutic potential against several psychiatric disorders. Nitric oxide (NO), an intercellular messenger has been suggested to play a crucial role in the pathogenesis of depression. The present study was designed to explore the possible involvement of NO mechanism in the protective effect of PQ against olfactory bulbectomy induced depression. Wistar rats were bulbectomized surgically and kept for a rehabilitation period of two weeks. PQ (50, 100 and 200 mg/kg; p.o.) alone and in combination with NO modulators like l-NAME (10 mg/kg, i.p.) and l-arginine (100 mg/kg; i.p.) were then administered daily for another two weeks. Ablation of olfactory bulbs caused depression-like symptoms as evidenced by increased immobility time in forced swim test, hyperactivity in open field arena, and anhedonic like response in sucrose preference test. Further, OBX caused elevation in serum corticosterone levels and increased oxidative–nitrosative damage. These deficits were integrated with increased levels of neuroinflammatory cytokines (TNF-α), apoptotic factor (caspase-3) and a marked reduction in neurogenesis factor (BDNF) in both cerebral cortex and hippocampal regions of bulbectomized rats. Treatment with PQ significantly and dose-dependently restored these behavioral, biochemical and molecular alterations associated with OBX. Further, pretreatment of l-NAME with subeffective dose of PQ (100 mg/kg) significantly potentiated its protective effects; however l-arginine pretreatment reversed the beneficial effects. The present study suggests that protective effect of P. quinquefolium might involve nitric oxide modulatory pathway against olfactory bulbectomy-induced depression in rats.

Resveratrol decreases inflammation in the brain of mice with mild traumatic brain injury

Following a mild traumatic brain injury (TBI) event, the secondary brain injury that persists after the initial blow to the head consists of excitotoxicity, decreased cerebral glucose levels, oxidant injury, mitochondrial dysfunction, inflammation, and neuronal cell death. To date, there are no effective interventions used at decreasing secondary brain injury after mild TBI. In this study, male mice were treated with either placebo or resveratrol (100 mg/kg) at 5 minutes and 12 hours after mild TBI. The mice were injured using the controlled cortical impact device. In this closed-head model, a midline incision was made to access the skull and the impactor tip was aligned on the sagittal suture midway between the bregma and lambda sutures. The mice were injured at a depth of 2.0 mm, velocity of 4 m/s, and a delay time of 100 milliseconds. At 72 hours following injury, the animals were intracardially perfused with 0.9% saline followed by 10% phosphate-buffered formalin. The whole brain was removed, sliced, and stained for microglial activation (Iba1). In addition, using the enzyme-linked immunosorbent assay, tissue levels of interleukin 6 (IL-6) and IL-12 were measured in the cerebral cortex and hippocampus. In this study, we found that in the placebo treatment group, there was a significant increase in Iba1 staining in the brain. The levels of microglial activation was reduced by resveratrol in the cerebral cortex (p < 0.001), corpus callosum (p < 0.001), and dentate gyrus (p < 0.005) brain regions after mild TBI. In addition to Iba1, resveratrol decreased the brain levels of IL-6 (p < 0.0001) and IL-12 (p < 0.004), which were observed in the hippocampus of the placebo group. In our model, no increase of IL-6 or IL-12 was observed in the cerebral cortex following TBI. Resveratrol given acutely after TBI results in a decrease in neuroinflammation. These results suggest that resveratrol may be beneficial in reducing secondary brain injury after experiencing a mild TBI.

Abstract WP297: A Mouse Model of Cerebral Microbleeds

Cerebral microbleeds are microscopic hemorrhages with deposits of blood products in the brain that can be visualized with MRI. Microbleeds are increased with age and in diseases such as cerebral amyloid angiopathy, hypertension, and stroke. There are few studies of either a) pathological correlates of cerebral microbleeds or b) imaging microscopic hemorrhage in brain tissue. The existing animal models of cerebral microbleeds involve transgenic mice (e.g. Tg2576) that spontaneously over-express β-amyloid, mimicking cerebral amyloid angiopathy. However, these models have limited use due to the fact that a) microbleeds may develop independent of amyloid deposition and b) the transgenic animals may require two years to fully develop microbleeds. In the current study, we used lipopolysaccharide (LPS) to induce cerebral microscopic hemorrhages over the course of several days. In this model, adult C57B6 mice (3 months of age) were injected with LPS (5mg/kg ip) or vehicle (phosphate buffered saline) at baseline and at 24 hr, and animals were sacrificed two days after initial injection. Mouse brains were analyzed for fresh hemorrhage using hematoxylin and eosin (H&amp;E) staining, iron deposition using Prussian blue staining, and blood-brain barrier (BBB) permeability by measuring sodium flouorescein (NaF) content. H&amp;E staining revealed small fresh hemorrhages visible grossly and microscopically in all animals treated with LPS, but not in control animals. Prussian blue staining revealed markedly increased iron deposition with LPS treatment, with positive stains in cerebral cortex, midbrain, and hippocampus regions. Quantification of Prussian blue staining revealed that LPS induced more than four-fold increase in number of positive stained foci (p&lt;.05 vs control). BBB permeability to NaF was increased from 2.9 ± 0.3 in control to 8.2 ± 1.8 ug NaF/g brain tissue in LPS-treated animals (p&lt;.05 vs control). In conclusion, this mouse model shows rapid production of cerebral microscopic hemorrhage, is associated with BBB dysfunction, and may be useful to study mechanistic and intervention strategies of cerebral microbleeds.

Cortical cerebral atrophy in patients with Parkinson’s disease: new trends in the diagnostics in vivo

The Parkinson’s disease (PD) pathology is not limited by degeneration of the nigrostriatal dopaminergic system, but includes also wide involvement of different regions of cerebral cortex. The aim of this study was the identification of differences in the brain cortical thickness in patients with early and advanced PD with the use of MRI morphometry. Sixty seven PD patients with Hoehn-Yahr 2 and 3 stages were examined. All patients underwent MRI with subsequent post-processing and receiving of cortical thickness parameters in different brain regions. Significant differences in the visual cortex, the cingulated and fusiform gyri and the frontopolar zone of a dominant hemisphere, and the Brodmann’s areas 1, 2, 3 and 4 of a non-dominant hemisphere were obtained. These data allow revealing relationships between non-motor manifestations of PD and degeneration of certain cortical regions of the brain.

Insulin Resistance: A Bridge between T2DM and Alzheimer’s Disease

T2DM is caused by insulin resistance in the tissues, no longer able to respond to the hormone action. It is most frequently associated with aging, a family history of diabetes, obesity, and failure of exercise.The insulin, ahormone produced by the beta-cells of the pancreas, is the key biomolecule for the regulation of carbohydrate and lipid metabolism. Although its action in body organs mainly concerns the glucose homeostasis, in Central Nervous System insulin performs several functions such as regulation of glucose metabolism, food intake and body weight, fertility and reproduction [1] and others not yet completely known. In particular, the high density of insulin receptors in the hippocampus and cerebral cortex regions has suggested its participation in learning and memory process. The administration of insulin to both humans and animal models has induced an enhancement of the memory function [2] and the treatment with insulin has given in several animal models beneficial effects to prevent memory loss after ischemia episodes whereas no effects are observed with glucose alone [3]. Insulin is also involved in the synaptic plasticity, for example, it as been show that insulin allows the long-lasting enhancement of GABA receptormediated synaptic transmission [4] and promote the internalization of AMPA receptors from the neuron synaptic membrane causing a long-term depression (LTD) of excitatory synaptic transmission in the hippocampus and cerebellum [5,6]. LTD is a process that, together with the opposite one, long-term potentiation has a great relevance for brain information storage and improvement of neurons links during development [7]. Furthermore, insulin receptor signaling regulates the maintenance of synapses and contributes to experience-dependent structural plasticity that is necessary for the recruitment of neurons into brain circuits [8]. Moreover, some studies suggest that insulin participates in neuronal differentiation of postnatal neural stem cell [9] and their culturing with both insulin and insulin-like growth factor (GF-1) causes a greater production of neurons during differentiation compared to culturesstimulated by IGF-1 alone [10]. Insulin also avoids the necrosis of rat embryonic neurons cultured in a serum-free medium; in fact the protein was capable to restore the cell viability by activation of Protein Kinase C, having the crucial role of controlling other proteins through the phosphorylation of their serine and threonine amino acid residues; on the contrary, insulinlike growth factor addition had no effect [11]. Clearly, in the insulin resistance state, these functions are impaired.

Collective Correlations of Brodmann Areas fMRI Study with RMT-Denoising

We study collective behavior of Brodmann regions of human cerebral cortex using functional Magnetic Resonance Imaging (fMRI) and Random Matrix Theory (RMT). The raw fMRI data is mapped onto the cortex regions corresponding to the Brodmann areas with the aid of the Talairach coordinates. Principal Component Analysis (PCA) of the Pearson correlation matrix for 41 different Brodmann regions is carried out to determine their collective activity in the idle state and in the active state stimulated by tapping. The collective brain activity is identified through the statistical analysis of the eigenvectors to the largest eigenvalues of the Pearson correlation matrix. The leading eigenvectors have a large participation ratio. This indicates that several Broadmann regions collectively give rise to the brain activity associated with these eigenvectors. We apply random matrix theory to interpret the underlying multivariate data.

Standardized Extract ofBacopa monnieraAttenuates Okadaic Acid Induced Memory Dysfunction in Rats: Effect on Nrf2 Pathway

The aim of the present study is to investigate the effect of standardized extract of Bacopa monnieri (memory enhancer) and Melatonin (an antioxidant) on nuclear factor erythroid 2 related factor 2 (Nrf2) pathway in Okadaic acid induced memory impaired rats. OKA (200 ng) was administered intracerebroventricularly (ICV) to induce memory impairment in rats. Bacopa monnieri (BM-40 and 80 mg/kg) and Melatonin (20 mg/kg) were administered 1 hr before OKA injection and continued daily up to day 13. Memory functions were assessed by Morris water maze test on days 13–15. Rats were sacrificed for biochemical estimations of oxidative stress, neuroinflammation, apoptosis, and molecular studies of Nrf2, HO1, and GCLC expressions in cerebral cortex and hippocampus brain regions. OKA caused a significant memory deficit with oxidative stress, neuroinflammation, and neuronal loss which was concomitant with attenuated expression of Nrf2, HO1, and GCLC. Treatment with BM and Melatonin significantly improved memory dysfunction in OKA rats as shown by decreased latency time and path length. The treatments also restored Nrf2, HO1, and GCLC expressions and decreased oxidative stress, neuroinflammation, and neuronal loss. Thus strengthening the endogenous defense through Nrf2 modulation plays a key role in the protective effect of BM and Melatonin in OKA induced memory impairment in rats.

Glucagon-like peptide-1 (GLP-1) raises blood-brain glucose transfer capacity and hexokinase activity in human brain

In hyperglycemia, glucagon-like peptide-1 (GLP-1) lowers brain glucose concentration together with increased net blood-brain clearance and brain metabolism, but it is not known whether this effect depends on the prevailing plasma glucose (PG) concentration. In hypoglycemia, glucose depletion potentially impairs brain function. Here, we test the hypothesis that GLP-1 exacerbates the effect of hypoglycemia. To test the hypothesis, we determined glucose transport and consumption rates in seven healthy men in a randomized, double-blinded placebo-controlled cross-over experimental design. The acute effect of GLP-1 on glucose transfer in the brain was measured by positron emission tomography (PET) during a hypoglycemic clamp (3 mM plasma glucose) with 18F-fluoro-2-deoxy-glucose (FDG) as tracer of glucose. In addition, we jointly analyzed cerebrometabolic effects of GLP-1 from the present hypoglycemia study and our previous hyperglycemia study to estimate the Michaelis-Menten constants of glucose transport and metabolism. The GLP-1 treatment lowered the vascular volume of brain tissue. Loading data from hypo- to hyperglycemia into the Michaelis-Menten equation, we found increased maximum phosphorylation velocity (Vmax) in the gray matter regions of cerebral cortex, thalamus, and cerebellum, as well as increased blood-brain glucose transport capacity (Tmax) in gray matter, white matter, cortex, thalamus, and cerebellum. In hypoglycemia, GLP-1 had no effects on net glucose metabolism, brain glucose concentration, or blood-brain glucose transport. Neither hexokinase nor transporter affinities varied significantly with treatment in any region. We conclude that GLP-1 changes blood-brain glucose transfer and brain glucose metabolic rates in a PG concentration-dependent manner. One consequence is that hypoglycemia eliminates these effects of GLP-1 on brain glucose homeostasis.

Anatomical Brain Images Alone Can Accurately Diagnose Chronic Neuropsychiatric Illnesses

ObjectiveDiagnoses using imaging-based measures alone offer the hope of improving the accuracy of clinical diagnosis, thereby reducing the costs associated with incorrect treatments. Previous attempts to use brain imaging for diagnosis, however, have had only limited success in diagnosing patients who are independent of the samples used to derive the diagnostic algorithms. We aimed to develop a classification algorithm that can accurately diagnose chronic, well-characterized neuropsychiatric illness in single individuals, given the availability of sufficiently precise delineations of brain regions across several neural systems in anatomical MR images of the brain.MethodsWe have developed an automated method to diagnose individuals as having one of various neuropsychiatric illnesses using only anatomical MRI scans. The method employs a semi-supervised learning algorithm that discovers natural groupings of brains based on the spatial patterns of variation in the morphology of the cerebral cortex and other brain regions. We used split-half and leave-one-out cross-validation analyses in large MRI datasets to assess the reproducibility and diagnostic accuracy of those groupings.ResultsIn MRI datasets from persons with Attention-Deficit/Hyperactivity Disorder, Schizophrenia, Tourette Syndrome, Bipolar Disorder, or persons at high or low familial risk for Major Depressive Disorder, our method discriminated with high specificity and nearly perfect sensitivity the brains of persons who had one specific neuropsychiatric disorder from the brains of healthy participants and the brains of persons who had a different neuropsychiatric disorder.ConclusionsAlthough the classification algorithm presupposes the availability of precisely delineated brain regions, our findings suggest that patterns of morphological variation across brain surfaces, extracted from MRI scans alone, can successfully diagnose the presence of chronic neuropsychiatric disorders. Extensions of these methods are likely to provide biomarkers that will aid in identifying biological subtypes of those disorders, predicting disease course, and individualizing treatments for a wide range of neuropsychiatric illnesses.