scholarly journals Long-Term Effects of Myoinositol on Behavioural Seizures and Biochemical Changes Evoked by Kainic Acid Induced Epileptogenesis

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Lia Tsverava ◽  
Manana Kandashvili ◽  
Giorgi Margvelani ◽  
Tamar Lortkipanidze ◽  
Georgi Gamkrelidze ◽  
...  
Keyword(s):  
Kainic Acid ◽  
Neurological Diseases ◽  
Treatment Strategies ◽  
Biochemical Changes ◽  
Mrna Levels ◽  
Long Term Effects ◽  
Molecular Changes ◽  
Acute Seizures ◽  
Spontaneous Recurrent Seizures

Epilepsy is one of the most devastating neurological diseases and despite significant efforts there is no cure available. Occurrence of spontaneous seizures in epilepsy is preceded by numerous functional and structural pathophysiological reorganizations in the brain—a process called epileptogenesis. Treatment strategies targeting this process may be efficient for preventing spontaneous recurrent seizures (SRS) in epilepsy, or for modification of disease progression. We have previously shown that (i) myoinositol (MI) pretreatment significantly decreases severity of acute seizures (status epilepticus: SE) induced by kainic acid (KA) in experimental animals and (ii) that daily post-SE administration of MI for 4 weeks prevents certain biochemical changes triggered by SE. However it was not established whether such MI treatment also exerts long-term effects on the frequency of SRS. In the present study we have shown that, in KA-induced post-SE epilepsy model in rats, MI treatment for 28 days reduces frequency and duration of behavioural SRS not only during the treatment, but also after its termination for the following 4 weeks. Moreover, MI has significant effects on molecular changes in the hippocampus, including mi-RNA expression spectrum, as well as mRNA levels of sodium-MI transporter and LRRC8A subunit of the volume regulated anionic channel. Taken together, these data suggest that molecular changes induced by MI treatment may counteract epileptogenesis. Thus, here we provide data indicating antiepileptogenic properties of MI, which further supports the idea of developing new antiepileptogenic and disease modifying drug that targets MI system.

Long-term effects of status epilepticus induced by kainic acid on hippocampal polyamines

Neuroreport ◽  
1998 ◽  
Vol 9 (5) ◽  
pp. 937-941 ◽  
Author(s):  
Lidia Giménez-Llort ◽  
Emili Martínez ◽  
Lluïsa Camón ◽  
Núria de Vera
Keyword(s):  
Status Epilepticus ◽  
Kainic Acid ◽  
Long Term Effects

scholarly journals Lactobacillus acidophilus stimulates the expression of SLC26A3 via a transcriptional mechanism

2010 ◽  
Vol 298 (3) ◽  
pp. G395-G401 ◽  
Author(s):  
Geetu Raheja ◽  
Varsha Singh ◽  
Ke Ma ◽  
Redouane Boumendjel ◽  
Alip Borthakur ◽  
...  
Keyword(s):  
Western Blot ◽  
Lactobacillus Acidophilus ◽  
Promoter Activity ◽  
In Vivo Studies ◽  
Mrna Levels ◽  
Long Term Effects ◽  
Exchange Activity

Clinical efficacy of probiotics in treating various forms of diarrhea has been clearly established. However, mechanisms underlying antidiarrheal effects of probiotics are not completely defined. Diarrhea is caused either by decreased absorption or increased secretion of electrolytes and solutes in the intestine. In this regard, the electroneutral absorption of two major electrolytes, Na+ and Cl−, occurs mainly through the coupled operation of Na+/H+ exchangers and Cl−/OH− exchangers. Previous studies from our laboratory have shown that Lactobacillus acidophilus (LA) acutely stimulated Cl−/OH− exchange activity via an increase in the surface levels of the apical anion exchanger SLC26A3 (DRA). However, whether probiotics influence SLC26A3 expression and promoter activity has not been examined. The present studies were, therefore, undertaken to investigate the long-term effects of LA on SLC26A3 expression and promoter activity. Treatment of Caco-2 cells with LA for 6–24 h resulted in a significant increase in Cl−/OH− exchange activity. DRA mRNA levels were also significantly elevated in response to LA treatment starting as early as 8 h. Additionally, the promoter activity of DRA was increased by more than twofold following 8 h LA treatment of Caco-2 cells. Similar to the in vitro studies, in vivo studies using mice gavaged with LA also showed significantly increased DRA mRNA (∼4-fold) and protein expression in the colonic regions as assessed by Western blot analysis and immunofluorescence. In conclusion, increase in DRA promoter activity and expression may contribute to the upregulation of intestinal electrolyte absorption and might underlie the potential antidiarrheal effects of LA.

Rodent models of early environment effects on offspring development and susceptibility to neurological diseases in adulthood

2012 ◽  
Vol 3 (3) ◽  
Author(s):  
Laurence Coutellier
Keyword(s):  
Environmental Conditions ◽  
Developmental Plasticity ◽  
Neurological Diseases ◽  
Adult Life ◽  
Later Life ◽  
Long Term Effects ◽  
Early Environment ◽  
Offspring Development ◽  
Early Life Events

AbstractEvents early in life can program brain for a pattern of neuroendocrine and behavioral responses in later life. This mechanism is named “developmental phenotypic plasticity”. Experimental evidences from rodents show that early experiences influence long-term development of behavioral, neuroendocrine and cognitive functions. While some neonatal conditions lead to positive outcomes, offspring might also display neurological dysfunctions in adulthood in case of adverse conditions during the early development. Different factors have been suggested to mediate the effects of neonatal conditions on offspring development but their exact contribution as well as their interaction still needs to be clarified. Studies based on rodents have been developed to model the long-term effects of early environmental conditions on the developing brain. These studies highlight importance of maternal behavior in mediating the effects of early environmental conditions on the offspring. However, other studies suggest that aside from the level of maternal care, other factors (gender, neonatal glucocorticoid levels) contribute to the adjustment of offspring phenotype to early environmental cues. Altogether, rodents-based evidence suggests that developmental plasticity is a very complex phenomenon mediated by multiple factors that interact one to each other. Ultimately, the goal is to understand how early life events can lead to advantageous phenotype in adult life, or, on the contrary, can predispose individuals to psychopathologies such as depression or anxiety.

scholarly journals Multiple Kainic Acid Seizures in the Immature and Adult Brain: Ictal Manifestations and Long-Term Effects on Learning and Memory

Epilepsia ◽  
1997 ◽  
Vol 38 (11) ◽  
pp. 1157-1166 ◽  
Author(s):  
Matthew R. Sarkisian ◽  
Pushpa Tandon ◽  
Zhao Liu ◽  
Yili Yang ◽  
Ariyuki Hori ◽  
...  
Keyword(s):  
Learning And Memory ◽  
Kainic Acid ◽  
Adult Brain ◽  
Long Term Effects

Evidence for a hyporesponsive limbic-hypothalamic-pituitary-adrenal axis following early-life repetitive hypoglycemia in adult male rats

2011 ◽  
Vol 301 (2) ◽  
pp. R484-R490 ◽  
Author(s):  
Ashton E. Lehmann ◽  
Kathleen Ennis ◽  
Michael K. Georgieff ◽  
Raghavendra Rao ◽  
Phu V. Tran
Keyword(s):  
Rat Model ◽  
Early Life ◽  
Regulatory Protein ◽  
Receptor Expression ◽  
Male Rats ◽  
Mrna Levels ◽  
Long Term Effects ◽  
Hypothalamic Pituitary Adrenal ◽  
Lhpa Axis

The developing limbic-hypothalamic-pituitary-adrenal (LHPA) axis is highly vulnerable to programming by early-life environmental factors, including exposure to synthetic glucocorticoids and nutrient deficiencies. Early-life repetitive hypoglycemia (RHG) is a common complication of insulin therapy for type-1 diabetes that may have long-term consequences in adulthood. Recent observations in a rat model of early RHG suggest persistent changes in LHPA axis function, including changes in relevant hormones and affective behaviors, which support a hyperresponsive LHPA axis. Thus, we hypothesized that early RHG would alter the expression of key genes regulating LHPA axis function in adulthood. The present study employed a rat model of insulin-induced RHG spanning postnatal days (P)24–28, a neurodevelopmental equivalent of early childhood in humans, to assess the long-term effects on mRNA levels for proteins relevant to the LHPA function and the corticosterone responses to ACTH stimulation of dispersed adrenocortical cells in vitro and restraint stress in vivo at adulthood. This early RHG model resulted in a hyporesponsive LHPA axis characterized by impaired corticosterone response, increased hippocampal glucocorticoid and mineralocorticoid receptor (GR and MR), decreased hypothalamic corticotropin-releasing hormone, increased adrenal steroidogenic-acute-regulatory protein and GR, and decreased adrenal MR, melanocortin-type-2 receptor and low-density lipoprotein receptor expression. Our findings highlight a complex environmental-gene interaction between RHG and LHPA axis during development that influences regulation of this axis in adulthood. The findings are consistent with the developmental origins of disease and underscore the influences of early-life events on the programming of a major regulatory system.

scholarly journals Lasting Effects of Intrauterine Exposure to Preeclampsia on Offspring and the Underlying Mechanism

2019 ◽  
Vol 09 (03) ◽  
pp. e275-e291 ◽  
Author(s):  
Hui Qing Lu ◽  
Rong Hu
Keyword(s):  
Clinical Management ◽  
Neurological Diseases ◽  
Large Body ◽  
Underlying Mechanism ◽  
Pregnancy Complication ◽  
Adverse Impact ◽  
Long Term Effects ◽  
Epidemiological Evidence ◽  
Short Term

AbstractPreeclampsia is a common pregnancy complication which can have adverse impact on both mother and baby. In addition to the short term effects, a large body of epidemiological evidence has found preeclampsia can exert long-lasting effects on mother and offspring. Studies suggest that offspring exposed to preeclampsia are at a higher risk of developing cardiovascular, metabolic, and neurological diseases, as well as other diseases. However, studies investigating the underlying mechanism are limited, the exact mechanism still remains unclear. In this study, we will review the epidemiological evidence and studies exploring the mechanism underlying long-term effects of preeclampsia on offspring. Further studies should be targeted at this field so as to implement effective clinical management to prevent the exposed offspring from potential diseases.

scholarly journals Effects of growth hormone treatment on the leptin system and on energy expenditure in abdominally obese men

1998 ◽  
pp. 408-414 ◽  
Author(s):  
C Karlsson ◽  
K Stenlof ◽  
G Johannsson ◽  
P Marin ◽  
P Bjorntorp ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Energy Expenditure ◽  
Double Blind Study ◽  
Mrna Levels ◽  
Long Term Effects ◽  
Gh Treatment ◽  
Double Blind ◽  
Serum Leptin ◽  
Leptin System

The present study has examined the short- and long-term effects of growth hormone (GH) treatment on the leptin system and energy expenditure. Thirty male individuals with abdominal obesity were randomised to GH or placebo treatment in a 9-month, double-blind study. The dose of GH was 9.5 microg/kg, administered subcutaneously every evening. Serum leptin concentrations were measured by a human leptin RIA. Total RNA was isolated from adipose tissue biopsies and leptin mRNA levels were determined by a semi-quantitative reverse transcriptase-PCR assay. Body composition was determined by potassium-40 and the basal metabolic rate (BMR) was measured by a computerised, ventilated, open-hood system. As compared with placebo, an overall decrease in serum leptin concentrations as assessed by the area under the curve (AUC) (P < 0.05) and an increase in BMR (AUC, P < 0.05) were observed during GH treatment. The overall GH-induced changes were due to marked changes in serum leptin concentrations and BMR after 6 weeks of treatment. After 9 months of GH treatment there was a significant reduction in body fat (BF) while serum leptin concentrations and BMR did not differ from baseline values. Leptin mRNA levels did not change over the study period. We speculate that long-term GH treatment induces a new energy balance steady state with decreased BF stores. The effects of GH on the leptin system is suggested to be of importance for the maintenance of a lower BF mass.

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