scholarly journals Glutathione Deficiency during Early Postnatal Development Causes Schizophrenia-Like Symptoms and a Reduction in BDNF Levels in the Cortex and Hippocampus of Adult Sprague–Dawley Rats

2021 ◽  
Vol 22 (12) ◽  
pp. 6171
Author(s):  
Marta Anna Lech ◽  
Monika Leśkiewicz ◽  
Kinga Kamińska ◽  
Zofia Rogóż ◽  
Elżbieta Lorenc-Koci
Keyword(s):  
Postnatal Development ◽  
Time Course ◽  
Postnatal Life ◽  
Positive Symptoms ◽  
Gbr 12909 ◽  
Sprague Dawley ◽  
Bdnf Mrna ◽  
Synthesis Inhibitor ◽  
Early Postnatal Development ◽  
Middle Adolescence

Growing body of evidence points to dysregulation of redox status in the brain as an important factor in the pathogenesis of schizophrenia. The aim of our study was to evaluate the effects of l-buthionine-(S,R)-sulfoximine (BSO), a glutathione (GSH) synthesis inhibitor, and 1-[2-Bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine dihydrochloride (GBR 12909), a dopamine reuptake inhibitor, given alone or in combination, to Sprague–Dawley pups during early postnatal development (p5–p16), on the time course of the onset of schizophrenia-like behaviors, and on the expression of brain-derived neurotrophic factor (BDNF) mRNA and its protein in the prefrontal cortex (PFC) and hippocampus (HIP) during adulthood. BSO administered alone decreased the levels of BDNF mRNA and its protein both in the PFC and HIP. Treatment with the combination of BSO + GBR 12909 also decreased BDNF mRNA and its protein in the PFC, but in the HIP, only the level of BDNF protein was decreased. Schizophrenia-like behaviors in rats were assessed at three time points of adolescence (p30, p42–p44, p60–p62) and in early adulthood (p90–p92) using the social interaction test, novel object recognition test, and open field test. Social and cognitive deficits first appeared in the middle adolescence stage and continued to occur into adulthood, both in rats treated with BSO alone or with the BSO + GBR 12909 combination. Behavior corresponding to positive symptoms in humans occurred in the middle adolescence period, only in rats treated with BSO + GBR 12909. Only in the latter group, amphetamine exacerbated the existing positive symptoms in adulthood. Our data show that rats receiving the BSO + GBR 12909 combination in the early postnatal life reproduced virtually all symptoms observed in patients with schizophrenia and, therefore, can be considered a valuable neurodevelopmental model of this disease.

scholarly journals Alterations in the Antioxidant Enzyme Activities in the Neurodevelopmental Rat Model of Schizophrenia Induced by Glutathione Deficiency during Early Postnatal Life

Antioxidants ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 538
Author(s):  
Magdalena Górny ◽  
Anna Bilska-Wilkosz ◽  
Małgorzata Iciek ◽  
Marta Hereta ◽  
Kinga Kamińska ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Postnatal Development ◽  
Postnatal Life ◽  
Antioxidant Enzyme Activities ◽  
Gbr 12909 ◽  
Sprague Dawley ◽  
Synthesis Inhibitor ◽  
Peripheral Tissues ◽  
Early Postnatal Development ◽  
Functional Changes

The aim of the present study was to assess the effects of l-buthionine-(S,R)-sulfoximine (BSO), a glutathione (GSH) synthesis inhibitor, and GBR 12909, a dopamine reuptake inhibitor, administered alone or in combination to Sprague-Dawley rats during early postnatal development (p5–p16), on the levels of reactive oxygen species (ROS), lipid peroxidation (LP) and the activities of antioxidant enzymes: superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione disulfide reductase (GR) in peripheral tissues (liver, kidney) and selected brain structures (prefrontal cortex, PFC; hippocampus, HIP; and striatum, STR) of 16-day-old rats. The studied parameters were analyzed with reference to the content of GSH and sulfur amino acids, methionine (Met) and cysteine (Cys) described in our previous study. This analysis showed that treatment with a BSO + GBR 12909 combination caused significant decreases in the lipid peroxidation levels in the PFC and HIP, in spite of there being no changes in ROS. The reduction of lipid peroxidation indicates a weakening of the oxidative power of the cells, and a shift in balance in favor of reducing processes. Such changes in cellular redox signaling in the PFC and HIP during early postnatal development may result in functional changes in adulthood.

scholarly journals Glutathione Deficiency and Alterations in the Sulfur Amino Acid Homeostasis during Early Postnatal Development as Potential Triggering Factors for Schizophrenia-Like Behavior in Adult Rats

Molecules ◽  
2019 ◽  
Vol 24 (23) ◽  
pp. 4253 ◽  
Author(s):  
Magdalena Górny ◽  
Agnieszka Wnuk ◽  
Adrianna Kamińska ◽  
Kinga Kamińska ◽  
Grażyna Chwatko ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Postnatal Development ◽  
Brain Structures ◽  
Global Dna Methylation ◽  
Gbr 12909 ◽  
Sprague Dawley ◽  
Synthesis Inhibitor ◽  
Adult Rats ◽  
Peripheral Tissues ◽  
Early Postnatal Development

Impaired glutathione (GSH) synthesis and dopaminergic transmission are important factors in the pathophysiology of schizophrenia. Our research aimed to assess the effects of l-buthionine-(S,R)-sulfoximine (BSO), a GSH synthesis inhibitor, and GBR 12909, a dopamine reuptake inhibitor, administered alone or in combination, to Sprague–Dawley rats during early postnatal development (p5–p16), on the levels of GSH, sulfur amino acids, global DNA methylation, and schizophrenia-like behavior. GSH, methionine (Met), homocysteine (Hcy), and cysteine (Cys) contents were determined in the liver, kidney, and in the prefrontal cortex (PFC) and hippocampus (HIP) of 16-day-old rats. DNA methylation in the PFC and HIP and schizophrenia-like behavior were assessed in adulthood (p90–p93). BSO caused the tissue-dependent decreases in GSH content and alterations in Met, Hcy, and Cys levels in the peripheral tissues and in the PFC and HIP. The changes in these parameters were accompanied by alterations in the global DNA methylation in the studied brain structures. Parallel to changes in the global DNA methylation, deficits in the social behaviors and cognitive functions were observed in adulthood. Only BSO + GBR 12909-treated rats exhibited behavioral alterations resembling positive symptoms in schizophrenia patients. Our results suggest the usefulness of this neurodevelopmental model for research on the pathomechanism of schizophrenia.

scholarly journals Impact of repeated co-treatment with escitalopram and aripiprazole on the schizophrenia-like behaviors and BDNF mRNA expression in the adult Sprague–Dawley rats exposed to glutathione deficit during early postnatal development of the brain

2021 ◽  
Author(s):  
Marta A. Lech ◽  
Kinga Kamińska ◽  
Monika Leśkiewicz ◽  
Elżbieta Lorenc-Koci ◽  
Zofia Rogóż
Keyword(s):  
Mrna Expression ◽  
Postnatal Development ◽  
Repeated Treatment ◽  
Sprague Dawley ◽  
Biochemical Tests ◽  
Bdnf Mrna ◽  
Adult Rats ◽  
Behavioral Deficits ◽  
Glutathione Synthesis ◽  
Early Postnatal Development

Abstract Background Preclinical and clinical studies have indicated that impaired endogenous synthesis of glutathione during early postnatal development plays a significant role in the pathophysiology of schizophrenia. Moreover, some studies have suggested that antidepressants are able to increase the activity of atypical antipsychotics which may efficiently improve the treatment of negative and cognitive symptoms of schizophrenia. Methods In the present study, we investigated the influence of repeated co-treatment with escitalopram and aripiprazole on the schizophrenia-like behavior and BDNF mRNA expression in adult rats exposed to glutathione deficit during early postnatal development. Male pups between the postnatal days p5–p16 were treated with the inhibitor of glutathione synthesis, BSO (L-buthionine-(S,R)-sulfoximine) and the dopamine uptake inhibitor, GBR 12,909 alone or in combination. Escitalopram and aripiprazole were given repeatedly for 21 days before the tests. On p90–92 rats were evaluated in the behavioral and biochemical tests. Results BSO given alone and together with GBR 12,909 induced deficits in the studied behavioral tests and decreased the expression of BDNF mRNA. Repeated aripiprazole administration at a higher dose reversed these behavioral deficits. Co-treatment with aripiprazole and an ineffective dose of escitalopram also abolished the behavioral deficits in the studied tests. Conclusion The obtained data indicated that the inhibition of glutathione synthesis in early postnatal development induced long-term deficits corresponding to schizophrenia-like behavior and decreased the BDNF mRNA expression in adult rats, and these behavioral deficits were reversed by repeated treatment with a higher dose of aripiprazole and also by co-treatment with aripiprazole and ineffective dose of escitalopram.

Quantitative changes in long-chain fatty acids during fetal and early postnatal development in rats

1992 ◽  
Vol 262 (1) ◽  
pp. R14-R19 ◽  
Author(s):  
S. C. Cunnane ◽  
Z. Y. Chen
Keyword(s):  
Fatty Acids ◽  
Postnatal Development ◽  
Essential Fatty Acids ◽  
Postnatal Life ◽  
Long Chain Fatty Acids ◽  
Early Postnatal Development ◽  
Liver Triacylglycerols ◽  
Quantitative Changes ◽  
Long Chain ◽  
Chain Fatty Acids

The quantitative importance of triacylglycerol as a source of total essential fatty acids during early postnatal development is reported in the accompanying article. Our objective here was to measure the quantitative changes in individual long-chain fatty acids in specific lipid classes of the carcass, liver, and brain of the developing rat mainly to describe the relative accumulation of long-chain vs. precursor fatty acids. Fatty acids in carcass phosphatidylcholine (micrograms/g) were lower at fetal days 18-21 than at either fetal day 15 or postnatal days +3 to +9. Individual long-chain fatty acids in liver phosphatidylcholine and phosphatidylethanolamine increased markedly by day +3 postnatally, whereas in brain phosphatidylethanolamine, the postnatal increase was delayed to between days +6 and +9. Fatty acids in carcass and liver triacylglycerols increased quantitatively by 10- to 300-fold from fetal day 21 to postnatal day +3 with amounts of both arachidonic and docosahexaenoic acid equaling linoleic acid. The ratios of linoleic and alpha-linolenic acids to respective long-chain products were significantly higher in triacylglycerols, whereas that of stearic to oleic acid was higher in phospholipids. We conclude that, during early postnatal life, oleic, linoleic, and alpha-linolenic acids are required in quantitatively greater amounts in triacylglycerols, whereas stearic acid and long-chain essential fatty acids are required in phospholipids.

scholarly journals In vivo MRI evaluation of early postnatal development in normal and impaired rat eyes

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jeannie M. Au ◽  
Swarupa Kancherla ◽  
Malack Hamade ◽  
Monica Mendoza ◽  
Kevin C. Chan
Keyword(s):  
Postnatal Development ◽  
Potassium Dichromate ◽  
Growth Patterns ◽  
Monocular Deprivation ◽  
Posterior Chamber ◽  
Sprague Dawley ◽  
Adult Rats ◽  
Early Postnatal Development ◽  
Magnetic Resonance Imaging Mri

AbstractThis study employed in vivo 7-T magnetic resonance imaging (MRI) to evaluate the postnatal ocular growth patterns under normal development or neonatal impairments in Sprague–Dawley rats. Using T2-weighted imaging on healthy rats from postnatal day (P) 1 (newborn) to P60 (adult), the volumes of the anterior chamber and posterior chamber (ACPC), lens, and vitreous humor increased logistically with ACPC expanding by 33-fold and the others by fivefold. Intravitreal potassium dichromate injection at P1, P7, and P14 led to T1-weighted signal enhancement in the developing retina by 188–289%. Upon unilateral hypoxic-ischemic encephalopathy at P7, monocular deprivation at P15, and monocular enucleation at P1, T2-weighted imaging of the adult rats showed decreased ocular volumes to different extents. In summary, in vivo high-field MRI allows for non-invasive evaluation of early postnatal development in the normal and impaired rat eyes. Chromium-enhanced MRI appeared effective in examining the developing retina before natural eyelid opening at P14 with relevance to lipid metabolism. The reduced ocular volumes upon neonatal visual impairments provided evidence to the emerging problems of why some impaired visual outcomes cannot be solely predicted by neurological assessments and suggested the need to look into both the eye and the brain under such conditions.

Absorption of glucose by lamb proximal colon measured during early postnatal development

1982 ◽  
Vol 98 (1) ◽  
pp. 161-165 ◽  
Author(s):  
M. W. Smith ◽  
P. S. James
Keyword(s):  
Glucose Transport ◽  
Time Course ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Proximal Colon ◽  
Postnatal Life ◽  
Early Postnatal Development ◽  
Rumen Development ◽  
Active Transport System

SUMMARYPieces of proximal colon taken from lambs during the first 2 weeks of postnatal life were incubated in vitro for measurement of short-circuit current and unidirectional glucose fluxes.The short-circuit current of colons taken from newborn and 1-day-old lambs was increased significantly in the presence of 5 mM D-glucose. This is taken as evidence for the presence of an active transport system for monosaccharides in this tissue. No such effect was seen using colons taken from 2-week-old lambs.Direct measurement of glucose transport showed a net absorption to take place across the proximal colon of newborn and 1-day-old lambs. There was no net movement across colons taken from lambs aged 1 week and over. Essentially similar results were obtained when measuring the amount of glucose influx inhibited by 10−5 M phloridzin.Colonic decline of glucose transport follows a time course different from that reported previously for the small intestine. It probably arises from rapid maturation of the colonic mucosa postnatally rather than from any gradual absence of substrate occurring during rumen development.

Postnatal Development Differentially Affects Voltage-Activated Calcium Currents in Respiratory Rhythmic Versus Nonrhythmic Neurons of the Pre-Bötzinger Complex

2005 ◽  
Vol 94 (2) ◽  
pp. 1423-1431 ◽  
Author(s):  
Frank P. Elsen ◽  
Jan-Marino Ramirez
Keyword(s):  
Postnatal Development ◽  
Calcium Current ◽  
Respiratory Rhythm ◽  
Calcium Currents ◽  
Postnatal Life ◽  
Rhythm Generation ◽  
Patch Clamp Technique ◽  
Early Postnatal Development ◽  
Bötzinger Complex ◽  
Respiratory Rhythm Generation

The mammalian respiratory network reorganizes during early postnatal life. We characterized the postnatal developmental changes of calcium currents in neurons of the pre-Bötzinger complex (pBC), the presumed site for respiratory rhythm generation. The pBC contains not only respiratory rhythmic (R) but also nonrhythmic neurons (nR). Both types of neurons express low- and high-voltage-activated (LVA and HVA) calcium currents. This raises the interesting issue: do calcium currents of the two co-localized neuron types have similar developmental profiles? To address this issue, we used the whole cell patch-clamp technique to compare in transverse slices of mice LVA and HVA calcium current amplitudes of the two neuron populations (R and nR) during the first and second postnatal week (P0–P16). The amplitude of HVA currents did not significantly change in R pBC-neurons (P0–P16), but it significantly increased in nR pBC-neurons during P8–P16. The dehydropyridine (DHP)-sensitive current amplitudes did not significantly change during the early postnatal development, suggesting that the observed amplitude changes in nR pBC-neurons are caused by (DHP) insensitive calcium currents. The ratio between HVA calcium current amplitudes dramatically changed during early postnatal development: At P0–P3, current amplitudes were significantly larger in R pBC-neurons, whereas at P8–P16, current amplitudes were significantly larger in nR pBC-neurons. Our results suggest that calcium currents in pBC neurons are differentially altered during postnatal development and that R pBC-neurons have fully expressed calcium currents early during postnatal development. This may be critical for stable respiratory rhythm generation in the underlying rhythm generating network.

scholarly journals Myocardial phospholipid remodeling under different types of load imposed during early postnatal development

2009 ◽  
pp. S13-S32
Author(s):  
F Novák ◽  
F Kolář ◽  
B Hamplová ◽  
L Mrnka ◽  
V Pelouch ◽  
...  
Keyword(s):  
Postnatal Development ◽  
Pressure Overload ◽  
Inhibitory Effect ◽  
Postnatal Life ◽  
Membrane Structures ◽  
Early Postnatal Development ◽  
Physiological Load ◽  
Acyl Chains ◽  
Membrane Bound ◽  
Normal Increase

Normal increase in hemodynamic load during early postnatal life is associated with heart growth and maturation of membrane structures that is accompanied by remodeling of membrane protein and lipid components. This review describes remodeling of phospholipids (PL) in rat myocardium during normal postnatal development and during accelerated cardiac growth induced by additional workload (aorta constriction, chronic hypoxia and hyperthyroidism) imposed on the heart early after birth. Normal physiological load after birth stimulates the development of membrane structures and synthesis of PL. While hyperthyroidism accelerates these processes, pressure overload has an inhibitory effect. These changes primarily influence the maturation of mitochondrial membranes as cardiolipin is one of the most affected PL species. The most sensitive part of PL structure in their remodeling process are PL acyl chains, particularly polyunsaturated fatty acids that are the key components determining the basic physicochemical properties of the membrane bilayer and thus the function of membrane-bound proteins and membrane-derived signaling lipid molecules. It is evident that PL remodeling may significantly influence both normal and pathological postnatal development of myocardium.

scholarly journals High-fat/fructose feeding during prenatal and postnatal development in female rats increases susceptibility to renal and metabolic injury later in life

2013 ◽  
Vol 304 (4) ◽  
pp. R278-R285 ◽  
Author(s):  
Elizabeth R. Flynn ◽  
Barbara T. Alexander ◽  
Jonathan Lee ◽  
Zachary M. Hutchens ◽  
Christine Maric-Bilkan
Keyword(s):  
Postnatal Development ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Female Rats ◽  
Postnatal Life ◽  
Standard Diet ◽  
Sprague Dawley ◽  
High Fat ◽  
Postnatal Environment ◽  
Prenatal And Postnatal Development

Accumulating evidence suggests that both an adverse prenatal and early postnatal environment increase susceptibility to renal and metabolic dysfunction later in life; however, whether exposure to adverse conditions during both prenatal and postnatal development act synergistically to potentiate the severity of renal and metabolic injury remains unknown. Sprague-Dawley rats were fed either a standard diet or a diet high in fat/fructose throughout pregnancy and lactation. After being weaned, female offspring were randomized to either standard diet or the high-fat/high-fructose diet, resulting in the following treatment groups: NF-NF, offspring of mothers fed a standard diet and fed a standard diet postnatally; NF-HF, offspring of mothers fed a standard diet and fed a high-fat/fructose diet postnatally; HF-NF, offspring of mothers fed a high-fat/fructose diet and fed a standard diet postnatally; HF-HF, offspring of mothers fed a high-fat/fructose diet and fed a high-fat/fructose diet postnatally. At the time of euthanasia (17 wk of age), HF-HF offspring weighed 30% more and had 110% more visceral fat than NF-NF offspring. The HF-HF offspring also had elevated blood glucose levels, glucose intolerance, 286% increase in urine albumin excretion, and 60% increase in glomerulosclerosis compared with NF-NF. In addition, HF-HF offspring exhibited a 100% increase in transforming growth factor-β protein expression and 116% increase in the abundance of infiltrated macrophages compared with the NF-NF offspring. These observations suggest that high-fat/fructose feeding during prenatal and throughout postnatal life increases the susceptibility to renal and metabolic injury later in life.

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