scholarly journals Sustained Energy Deficit Following Perinatal Asphyxia: A Shift towards the Fructose-2,6-bisphosphatase (TIGAR)-Dependent Pentose Phosphate Pathway and Postnatal Development

Antioxidants ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 74
Author(s):  
Carolyne Lespay-Rebolledo ◽  
Andrea Tapia-Bustos ◽  
Ronald Perez-Lobos ◽  
Valentina Vio ◽  
Emmanuel Casanova-Ortiz ◽  
...  
Keyword(s):  
Pentose Phosphate Pathway ◽  
Perinatal Asphyxia ◽  
Redox Homeostasis ◽  
Brain Regions ◽  
Pentose Phosphate ◽  
Energy Deficit ◽  
Long Term Effects ◽  
Sustained Effect ◽  
Dependent Cell ◽  
The Brain

Labor and delivery entail a complex and sequential metabolic and physiologic cascade, culminating in most circumstances in successful childbirth, although delivery can be a risky episode if oxygen supply is interrupted, resulting in perinatal asphyxia (PA). PA causes an energy failure, leading to cell dysfunction and death if re-oxygenation is not promptly restored. PA is associated with long-term effects, challenging the ability of the brain to cope with stressors occurring along with life. We review here relevant targets responsible for metabolic cascades linked to neurodevelopmental impairments, that we have identified with a model of global PA in rats. Severe PA induces a sustained effect on redox homeostasis, increasing oxidative stress, decreasing metabolic and tissue antioxidant capacity in vulnerable brain regions, which remains weeks after the insult. Catalase activity is decreased in mesencephalon and hippocampus from PA-exposed (AS), compared to control neonates (CS), in parallel with increased cleaved caspase-3 levels, associated with decreased glutathione reductase and glutathione peroxidase activity, a shift towards the TIGAR-dependent pentose phosphate pathway, and delayed calpain-dependent cell death. The brain damage continues long after the re-oxygenation period, extending for weeks after PA, affecting neurons and glial cells, including myelination in grey and white matter. The resulting vulnerability was investigated with organotypic cultures built from AS and CS rat newborns, showing that substantia nigra TH-dopamine-positive cells from AS were more vulnerable to 1 mM of H2O2 than those from CS animals. Several therapeutic strategies are discussed, including hypothermia; N-acetylcysteine; memantine; nicotinamide, and intranasally administered mesenchymal stem cell secretomes, promising clinical translation.

Regionally Impaired Redox Homeostasis in the Brain of Rats Subjected to Global Perinatal Asphyxia: Sustained Effect up to 14 Postnatal Days

2018 ◽  
Vol 34 (3) ◽  
pp. 660-676 ◽  
Author(s):  
Carolyne Lespay-Rebolledo ◽  
Ronald Perez-Lobos ◽  
Andrea Tapia-Bustos ◽  
Valentina Vio ◽  
Paola Morales ◽  
...  
Keyword(s):  
Perinatal Asphyxia ◽  
Redox Homeostasis ◽  
Sustained Effect ◽  
The Brain

scholarly journals Functional Connectivity within Brain Networks of Long Term and Short term Meditators

2019 ◽  
Vol 9 (2S) ◽  
pp. 29-34
Keyword(s):  
Functional Connectivity ◽  
Temporal Correlation ◽  
Brain Regions ◽  
Invasive Technique ◽  
Long Term Effects ◽  
Short Term ◽  
Statistical Concept ◽  
The Brain ◽  
Meditative Practices

Meditation refers to a state of mind of relaxation and concentration, where generally the mind and body is at rest. The process of meditation reflects the state of the brain which is distinct from sleep or typical wakeful states of consciousness. Meditative practices usually involve regulation of emotions and monitoring of attention. Over the past decade there has been a tremendous increase in an interest to study the neural mechanisms involved in meditative practices. It could also be beneficial to explore if the effect of meditation is altered by the number of years of meditation practice. Functional Magnetic Resonance Imaging (fMRI) is a very useful imaging technique which can be used to perform this analysis due to its inherent benefits, mainly it being a non-invasive technique. Functional activation and connectivity analysis can be performed on the fMRI data to find the active regions and the connectivity in the brain regions. Functional connectivity is defined as a simple temporal correlation between anatomically separate, active neural regions. Functional connectivity gives the statistical dependencies between regional time series. It is a statistical concept and is quantified using metrics like Correlation. In this study, a comparison is made between functional connectivity in the brain regions of long term meditation practitioners (LTP) and short-term meditation practitioners (STP) to see the differences and similarities in the connectivity patterns. From the analysis, it is evident that in fact there is a difference in connectivity between long term and short term practitioners and hence continuous practice of meditation can have long term effects.

scholarly journals Wnt5a Increases the Glycolytic Rate and the Activity of the Pentose Phosphate Pathway in Cortical Neurons

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Pedro Cisternas ◽  
Paulina Salazar ◽  
Carmen Silva-Álvarez ◽  
L. Felipe Barros ◽  
Nibaldo C. Inestrosa
Keyword(s):  
Glucose Metabolism ◽  
Wnt Signaling ◽  
Pentose Phosphate Pathway ◽  
Neurodegenerative Disorders ◽  
Metabolic Flux ◽  
High Energy ◽  
Pentose Phosphate ◽  
The Brain ◽  
Glycolytic Rate

In the last few years, several reports have proposed that Wnt signaling is a general metabolic regulator, suggesting a role for this pathway in the control of metabolic flux. Wnt signaling is critical for several neuronal functions, but little is known about the correlation between this pathway and energy metabolism. The brain has a high demand for glucose, which is mainly used for energy production. Neurons use energy for highly specific processes that require a high energy level, such as maintaining the electrical potential and synthesizing neurotransmitters. Moreover, an important metabolic impairment has been described in all neurodegenerative disorders. Despite the key role of glucose metabolism in the brain, little is known about the cellular pathways involved in regulating this process. We report here that Wnt5a induces an increase in glucose uptake and glycolytic rate and an increase in the activity of the pentose phosphate pathway; the effects of Wnt5a require the intracellular generation of nitric oxide. Our data suggest that Wnt signaling stimulates neuronal glucose metabolism, an effect that could be important for the reported neuroprotective role of Wnt signaling in neurodegenerative disorders.

scholarly journals The pentose phosphate pathway regulates chronic neuroinflammation and dopaminergic neurodegeneration

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Dezhen Tu ◽  
Yun Gao ◽  
Ru Yang ◽  
Tian Guan ◽  
Jau-Shyong Hong ◽  
...  
Keyword(s):  
Substantia Nigra ◽  
Pentose Phosphate Pathway ◽  
Microglial Activation ◽  
Redox Homeostasis ◽  
Pentose Phosphate ◽  
Transgenic Expression ◽  
Dopaminergic Neurodegeneration ◽  
Locomotor Impairment

Abstract Background Metabolic dysfunction and neuroinflammation are increasingly implicated in Parkinson’s disease (PD). The pentose phosphate pathway (PPP, a metabolic pathway parallel to glycolysis) converts glucose-6-phosphate into pentoses and generates ribose-5-phosphate and NADPH thereby governing anabolic biosynthesis and redox homeostasis. Brains and immune cells display high activity of glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the PPP. A postmortem study reveals dysregulation of G6PD enzyme in brains of PD patients. However, spatial and temporal changes in activity/expression of G6PD in PD remain undetermined. More importantly, it is unclear how dysfunction of G6PD and the PPP affects neuroinflammation and neurodegeneration in PD. Methods We examined expression/activity of G6PD and its association with microglial activation and dopaminergic neurodegeneration in multiple chronic PD models generated by an intranigral/intraperitoneal injection of LPS, daily subcutaneous injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 6 days, or transgenic expression of A53T α-synuclein. Primary microglia were transfected with G6PD siRNAs and treated with lipopolysaccharide (LPS) to examine effects of G6PD knockdown on microglial activation and death of co-cultured neurons. LPS alone or with G6PD inhibitor(s) was administrated to mouse substantia nigra or midbrain neuron-glia cultures. While histological and biochemical analyses were conducted to examine microglial activation and dopaminergic neurodegeneration in vitro and in vivo, rotarod behavior test was performed to evaluate locomotor impairment in mice. Results Expression and activity of G6PD were elevated in LPS-treated midbrain neuron-glia cultures (an in vitro PD model) and the substantia nigra of four in vivo PD models. Such elevation was positively associated with microglial activation and dopaminergic neurodegeneration. Furthermore, inhibition of G6PD by 6-aminonicotinamide and dehydroepiandrosterone and knockdown of microglial G6PD attenuated LPS-elicited chronic dopaminergic neurodegeneration. Mechanistically, microglia with elevated G6PD activity/expression produced excessive NADPH and provided abundant substrate to over-activated NADPH oxidase (NOX2) leading to production of excessive reactive oxygen species (ROS). Knockdown and inhibition of G6PD ameliorated LPS-triggered production of ROS and activation of NF-кB thereby dampening microglial activation. Conclusions Our findings indicated that G6PD-mediated PPP dysfunction and neuroinflammation exacerbated each other mediating chronic dopaminergic neurodegeneration and locomotor impairment. Insight into metabolic-inflammatory interface suggests that G6PD and NOX2 are potential therapeutic targets for PD.

scholarly journals A systematic review of neuroimaging and acute cannabis exposure in age-of-risk for psychosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lani Cupo ◽  
Eric Plitman ◽  
Elisa Guma ◽  
M. Mallar Chakravarty
Keyword(s):  
Chronic Exposure ◽  
Brain Regions ◽  
Acute Exposure ◽  
Psychotic Symptoms ◽  
Long Term Effects ◽  
Symptom Dimensions ◽  
Increased Risk ◽  
The Impact ◽  
The Brain

AbstractAcute exposure to cannabis has been associated with an array of cognitive alterations, increased risk for neuropsychiatric illness, and other neuropsychiatric sequelae including the emergence of acute psychotic symptoms. However, the brain alterations associating cannabis use and these behavioral and clinical phenotypes remains disputed. To this end, neuroimaging can be a powerful technique to non-invasively study the impact of cannabis exposure on brain structure and function in both humans and animal models. While chronic exposure studies provide insight into how use may be related to long-term outcomes, acute exposure may reveal interesting information regarding the immediate impact of use and abuse on brain circuits. Understanding these alterations could reveal the connection with symptom dimensions in neuropsychiatric disorders and, more specifically with psychosis. The purpose of the present review is to: 1) provide an update on the findings of pharmacological neuroimaging studies examining the effects of administered cannabinoids and 2) focus the discussion on studies that examine the sensitive window for the emergence of psychosis. Current literature indicates that cannabis exposure has varied effects on the brain, with the principal compounds in cannabis (delta-9-tetrahydrocannabinol and cannabidiol) altering activity across different brain regions. Importantly, we also discovered critical gaps in the literature, particularly regarding sex-dependent responses and long-term effects of chronic exposure. Certain networks often characterized as dysregulated in psychosis, like the default mode network and limbic system, were also impacted by THC exposure, identifying areas of particular interest for future work investigating the potential relationship between the two.

scholarly journals Quantitative Importance of the Pentose Phosphate Pathway Determined by Incorporation of 13C from [2-13C]- and [3-13C]Glucose into TCA Cycle Intermediates and Neurotransmitter Amino Acids in Functionally Intact Neurons

2012 ◽  
Vol 32 (9) ◽  
pp. 1788-1799 ◽  
Author(s):  
Eva M F Brekke ◽  
Anne B Walls ◽  
Arne Schousboe ◽  
Helle S Waagepetersen ◽  
Ursula Sonnewald
Keyword(s):  
Amino Acids ◽  
Pentose Phosphate Pathway ◽  
Cortical Neurons ◽  
Tca Cycle ◽  
Pentose Phosphate ◽  
Cerebellar Neurons ◽  
The Tca Cycle ◽  
Intact Brain ◽  
Tca Cycle Intermediates ◽  
The Brain

The brain is highly susceptible to oxidative injury, and the pentose phosphate pathway (PPP) has been shown to be affected by pathological conditions, such as Alzheimer's disease and traumatic brain injury. While this pathway has been investigated in the intact brain and in astrocytes, little is known about the PPP in neurons. The activity of the PPP was quantified in cultured cerebral cortical and cerebellar neurons after incubation in the presence of [2-13C]glucose or [3-13C]glucose. The activity of the PPP was several fold lower than glycolysis in both types of neurons. While metabolism of 13C-labeled glucose via the PPP does not appear to contribute to the production of releasable lactate, it contributes to labeling of tricarboxylic acid (TCA) cycle intermediates and related amino acids. Based on glutamate isotopomers, it was calculated that PPP activity accounts for ∼6% of glucose metabolism in cortical neurons and ∼4% in cerebellar neurons. This is the first demonstration that pyruvate generated from glucose via the PPP contributes to the synthesis of acetyl CoA for oxidation in the TCA cycle. Moreover, the fact that 13C labeling from glucose is incorporated into glutamate proves that both the oxidative and the nonoxidative stages of the PPP are active in neurons.

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