Hippocampal brain amines in methotrexate-induced learning and memory deficit

2002 ◽  
Vol 80 (11) ◽  
pp. 1076-1084 ◽  
Author(s):  
Sampath Madhyastha ◽  
S N Somayaji ◽  
M S Rao ◽  
K Nalini ◽  
K Laxminarayana Bairy
Keyword(s):  
Learning And Memory ◽  
Cognitive Dysfunction ◽  
Conditioned Avoidance ◽  
Term Treatment ◽  
Cresyl Violet ◽  
Intrathecal Methotrexate ◽  
Avoidance Task ◽  
Therapeutic Implications ◽  
Brain Amines ◽  
Long Term Treatment

Intrathecal methotrexate in children with leukemia is known to cause seizures, dementia, leukoencephalo pathy, and cognitive dysfunction after long-term treatment. To investigate the cognitive dysfunction, male Wistar rats were given multiple intracerebroventricular injections of methotrexate. Its effect on behaviour was tested in the two-compartment conditioned avoidance task and dark–bright arena test. Levels of brain amines in the hippocampal region of the brain were estimated by HPLC. The qualitative and quantitative histopathological changes in the different regions of the hippocampus were studied by cresyl violet staining. Multiple injections (1 or 2 mg/kg) produced convulsions and learning and memory impairment but did not induce anxiolytic activity. They also reduced concentrations of all three brain amines (norepinephrine, dopamine, and serotonin) and the serotonin metabolite 5-hydroxyindoleacetic acid. The CA4 region of the hippocampus was severely affected by intraventricular methotrexate. Disruption of brain monoamines has been proposed as a cause of brain dysfunction from this chemotherapy, and that disruption may in turn involve cytotoxic effects of methotrexate on brain tissue. The outcomes of this study may have therapeutic implications in the management of cancer conditions, particularly in childhood lymphoblastic leukemia.Key words: methotrexate, hippocampus, norepinephrine, dopamine, serotonin, learning and memory.

Do statins impair learning and memory after long-term treatment – comparative experimental study

2017 ◽  
Vol 27 ◽  
pp. S683
Author(s):  
M. Georgieva-Kotetarova ◽  
I. Kostadinova ◽  
D. Delev ◽  
I. Kostadinov ◽  
H. Zlatanova ◽  
...  
Keyword(s):  
Experimental Study ◽  
Learning And Memory ◽  
Term Treatment ◽  
Long Term Treatment

scholarly journals Therapeutic Implications of Targeting AKT Signaling in Melanoma

2011 ◽  
Vol 2011 ◽  
pp. 1-20 ◽  
Author(s):  
SubbaRao V. Madhunapantula ◽  
Gavin P. Robertson
Keyword(s):  
Pi3k Pathway ◽  
Term Treatment ◽  
Negative Regulator ◽  
Phosphatase And Tensin Homolog ◽  
Key Enzymes ◽  
Therapeutic Implications ◽  
Cellular Processes ◽  
Tensin Homolog ◽  
Stage Disease ◽  
Long Term Treatment

Identification of key enzymes regulating melanoma progression and drug resistance has the potential to lead to the development of novel, more effective targeted agents for inhibiting this deadly form of skin cancer. The Akt3, also known as protein kinase B gamma, pathway enzymes regulate diverse cellular processes including proliferation, survival, and invasion thereby promoting the development of melanoma. Accumulating preclinical evidence demonstrates that therapeutic agents targeting these kinases alone or in combination with other pathway members could be effective for the long-term treatment of advanced-stage disease. However, currently, no selective and effective therapeutic agent targeting these kinases has been identified for clinical use. This paper provides an overview of the key enzymes of the PI3K pathway with emphasis placed on Akt3 and the negative regulator of this kinase called PTEN (phosphatase and tensin homolog deleted on chromosome 10). Mechanisms regulating these enzymes, their substrates and therapeutic implications of targeting these proteins to treat melanoma are also discussed. Finally, key issues that remain to be answered and future directions for interested researchers pertaining to this signaling cascade are highlighted.

scholarly journals Effects of Gintonin-Enriched Fraction on Methylmercury-Induced Neurotoxicity and Organ Methylmercury Elimination

2020 ◽  
Vol 17 (3) ◽  
pp. 838
Author(s):  
Hyeon-Joong Kim ◽  
Sun-Hye Choi ◽  
Na-Eun Lee ◽  
Hee-Jung Cho ◽  
Hyewhon Rhim ◽  
...  
Keyword(s):  
Learning And Memory ◽  
Neural Progenitor Cells ◽  
Term Treatment ◽  
Dependent Manner ◽  
Protective Effects ◽  
Independent Manner ◽  
Long Term Treatment ◽  
Liver And Kidney

Gintonin is a newly discovered ingredient of ginseng and plays an exogenous ligand for G protein-coupled lysophosphatidic acid receptors. We previously showed that gintonin exhibits diverse effects from neurotransmitter release to improvement of Alzheimer’s disease-related cognitive dysfunctions. However, previous studies did not show whether gintonin has protective effects against environmental heavy metal. We investigated the effects of gintonin-enriched fraction (GEF) on methylmercury (MeHg)-induced neurotoxicity and learning and memory dysfunction and on organ MeHg elimination. Using hippocampal neural progenitor cells (hNPCs) and mice we examined the effects of GEF on MeHg-induced hippocampal NPC neurotoxicity, on formation of reactive oxygen species (ROS), and on in vivo learning and memory functions after acute MeHg exposure. Treatment of GEF to hNPCs attenuated MeHg-induced neurotoxicity with concentration- and time-dependent manner. GEF treatment inhibited MeHg- and ROS inducer-induced ROS formations. Long-term treatment of GEF also improved MeHg-induced learning and memory dysfunctions. Oral administration of GEF decreased the concentrations of MeHg in blood, brain, liver, and kidney. This is the first report that GEF attenuated MeHg-induced in vitro and in vivo neurotoxicities through LPA (lysophosphatidic acids) receptor-independent manner and increased organ MeHg elimination. GEF-mediated neuroprotection might achieve via inhibition of ROS formation and facilitation of MeHg elimination from body.

Are we able to influence cognitive dysfunction in multiple sclerosis?

2016 ◽  
Vol 33 (S1) ◽  
pp. S367-S367
Author(s):  
E.I. Davidescu ◽  
S.A. Nicolae ◽  
I. Buraga ◽  
C. Tudose ◽  
N. Popa
Keyword(s):  
Multiple Sclerosis ◽  
Cognitive Dysfunction ◽  
Short Form ◽  
Term Treatment ◽  
Cognitive Status ◽  
Cortical Atrophy ◽  
Long Term Treatment ◽  
Cognitive Disturbances ◽  
Concentration Changes ◽  
Competing Interest

IntroductionMultiple sclerosis (MS) is the most common chronic neurologic disease affecting young people. Cognitive dysfunction is an important part of disability, interfering with quality of life (QoL). Disease modifying therapies (DMT) are gold standard of long-term treatment in MS.ObjectivesAssessment of DMT impact on evolution of cognitive dysfunction.AimsTo analyze the cognitive status in a lot of 74 patients with MS, with a mean age of 40.4 years, treated with different DMT in the National Health Program.MethodsTesting patients during 2014–2015 for cognitive dysfunction, by applying MMSE, Sunderland Clock Test, Beck Depression Inventory, Fatigue Impact Scale and QoL Short form-36 scores every 6 months; analyzing demographic, clinical and magnetic resonance imagery (MRI) data.ResultsThirty-six percent of lot showed memory and concentration changes (12 patients with secondary progressive MS, 15 with relapsing-remitting MS); mean age of these patients was 46.29 years, with a mean period of evolution of the disease of 9.8 years before starting DMT; cortical atrophy was present on MRI in 37% of these patients. Mean age of those who didn’t present cognitive disturbances was 37.01 years, with a mean period of evolution of 6.2 years before starting DMT. Disturbances appeared independently of the presence of cortical atrophy, as this marker appeared in 5% of patients with no cognitive dysfunction.ConclusionsWhen starting DMT, age and time of evolution of the disease are essential for further developing of cognitive dysfunction. Mood and anxiety disturbances can be a prodromal marker of neurocognitive troubles. DMT have neuroprotective outcome in MS.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Immunosuppressive and glucocorticoid therapy for the treatment of ANCA-asssociated vasculitis

Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_3) ◽  
pp. iii60-iii67 ◽  
Author(s):  
Irmgard Neumann
Keyword(s):  
Management Strategies ◽  
Term Treatment ◽  
Individual Risk ◽  
High Dose ◽  
Therapeutic Implications ◽  
Long Term Treatment ◽  
Life Threatening ◽  
Individual Risk Factors ◽  
Chronic Autoimmune Disease

Abstract ANCA-associated vasculitis (AAV) is a systemic, potentially organ and life threatening chronic autoimmune disease. With current management strategies, such as high-dose glucocorticoids in combination with cyclophosphamide or rituximab, outcomes have progressively improved with overall remission rates of 70–90%. However, relapse rates after discontinuation of therapy are consistently high, and treatment-related toxicity, mainly driven by glucocorticoids, still determines morbidity and quality of life. Prevention of relapses while minimizing adverse events is a major goal of long-term treatment, but the optimal duration of maintenance therapy and the role and utility of glucocorticoids in this context remains controversial. This review of induction and maintenance treatment of AAV aims to offer practical advice on immunosuppressive therapies and patient care, addressing individual risk factors and their therapeutic implications. It will discuss benefits and harms of the use of glucocorticoids, particularly focusing on recent advances in steroid sparing concepts.

Hypnotherapy is effective in the long-term treatment of functional dyspepsia

2001 ◽  
Vol 120 (5) ◽  
pp. A115-A115 ◽  
Author(s):  
E CALVERT ◽  
L HOUGHTON ◽  
P COOPER ◽  
P WHORWELL
Keyword(s):  
Functional Dyspepsia ◽  
Term Treatment ◽  
Long Term Treatment
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