Method for the identification of pharmacological intervention for the disruption of fear memory in PTSD-rat model

Decompression sickness (DCS) with alterations in coagulation system and formation of platelet thrombi occurs when a subject is subjected to a reduction in environmental pressure. Blood platelet consumption after decompression is clearly linked to bubble formation in humans and offers an index for evaluating DCS severity in animal models. Previous studies highlighted a predominant involvement of platelet activation and thrombin generation in bubble-induced platelet aggregation (BIPA). To study the mechanism of the BIPA in DCS, we examined the effect of acetylsalicylic acid (ASA), heparin (Hep), and clopidogrel (Clo), with anti-thrombotic dose pretreatment in a rat model of DCS. Male Sprague-Dawley rats ( n = 208) were randomly assigned to one experimental group treated before the hyperbaric exposure and decompression protocol either with ASA (3×100 mg·kg−1·day−1, n = 30), Clo (50 mg·kg−1·day−1, n = 60), Hep (500 IU/kg, n = 30), or to untreated group ( n = 49). Rats were first compressed to 1,000 kPa (90 msw) for 45 min and then decompressed to surface in 38 min. In a control experiment, rats were treated with ASA ( n = 13), Clo ( n = 13), or Hep ( n = 13) and maintained at atmospheric pressure for an equivalent period of time. Onset of DCS symptoms and death were recorded during a 60-min observation period after surfacing. DCS evaluation included pulmonary and neurological signs. Blood samples for platelet count (PC) were taken 30 min before hyperbaric exposure and 30 min after surfacing. Clo reduces the DCS mortality risk (mortality rate: 3/60 with Clo, 15/30 with ASA, 21/30 with Hep, and 35/49 in the untreated group) and DCS severity (neurological DCS incidence: 9/60 with Clo, 6/30 with ASA, 5/30 with Hep, and 12/49 in the untreated group). Clo reduced fall in platelet count and BIPA (−4,5% with Clo, −19.5% with ASA, −19,9% with Hep, and −29,6% in the untreated group). ASA, which inhibits the thromboxane A2 pathway, and Hep, which inhibits thrombin generation, have no protective effect on DCS incidence. Clo, a specific ADP-receptor antagonist, reduces post-decompression platelet consumption. These results point to the predominant involvement of the ADP release in BIPA but cannot differentiate definitively between bubble-induced vessel wall injury and bubble-blood component interactions in DCS.

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trans-Resveratrol ameliorates anxiety-like behaviors and fear memory deficits in a rat model of post-traumatic stress disorder

Neuropharmacology ◽

10.1016/j.neuropharm.2017.12.035 ◽

2018 ◽

Vol 133 ◽

pp. 181-188 ◽

Cited By ~ 14

Author(s):

Gaowen Li ◽

Gang Wang ◽

Jing Shi ◽

Xueyi Xie ◽

Ning Fei ◽

...

Keyword(s):

Rat Model ◽

Post Traumatic Stress Disorder ◽

Traumatic Stress ◽

Stress Disorder ◽

Memory Deficits ◽

Fear Memory ◽

Post Traumatic Stress ◽

Post Traumatic

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Sustained correction of associative learning deficits after brief, early treatment in a rat model of Fragile X Syndrome

Science Translational Medicine ◽

10.1126/scitranslmed.aao0498 ◽

2019 ◽

Vol 11 (494) ◽

pp. eaao0498 ◽

Cited By ~ 17

Author(s):

Antonis Asiminas ◽

Adam D. Jackson ◽

Susana R. Louros ◽

Sally M. Till ◽

Teresa Spano ◽

...

Keyword(s):

Associative Learning ◽

Fragile X Syndrome ◽

Associative Memory ◽

Rat Model ◽

Fragile X ◽

Time Windows ◽

Treatment Strategies ◽

Developmental Time ◽

Developmental Trajectory ◽

Pharmacological Intervention

Fragile X Syndrome (FXS) is one of the most common monogenic forms of autism and intellectual disability. Preclinical studies in animal models have highlighted the potential of pharmaceutical intervention strategies for alleviating the symptoms of FXS. However, whether treatment strategies can be tailored to developmental time windows that define the emergence of particular phenotypes is unknown. Similarly, whether a brief, early intervention can have long-lasting beneficial effects, even after treatment cessation, is also unknown. To address these questions, we first examined the developmental profile for the acquisition of associative learning in a rat model of FXS. Associative memory was tested using a range of behavioral paradigms that rely on an animal’s innate tendency to explore novelty. Fmr1 knockout (KO) rats showed a developmental delay in their acquisition of object-place recognition and did not demonstrate object-place-context recognition paradigm at any age tested (up to 23 weeks of age). Treatment of Fmr1 KO rats with lovastatin between 5 and 9 weeks of age, during the normal developmental period that this associative memory capability is established, prevents the emergence of deficits but has no effect in wild-type animals. Moreover, we observe no regression of cognitive performance in the FXS rats over several months after treatment. This restoration of the normal developmental trajectory of cognitive function is associated with the sustained rescue of both synaptic plasticity and altered protein synthesis. The findings provide proof of concept that the impaired emergence of the cognitive repertoire in neurodevelopmental disorders may be prevented by brief, early pharmacological intervention.

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Ameliorative Effects of Bredemolic Acid on Markers Associated with Renal Dysfunction in a Diet-Induced Prediabetic Rat Model

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/2978340 ◽

2020 ◽

Vol 2020 ◽

pp. 1-12

Author(s):

Akinjide Moses Akinnuga ◽

Angezwa Siboto ◽

Bongiwe Khumalo ◽

Ntethelelo Hopewell Sibiya ◽

Phikelelani Ngubane ◽

...

Keyword(s):

Mrna Expression ◽

Renal Dysfunction ◽

Rat Model ◽

Plasma Concentrations ◽

Normal Diet ◽

Male Rats ◽

Pharmacological Intervention ◽

Sprague Dawley ◽

Prediabetic State ◽

Diet Modification

Recently, studies have shown that renal dysfunction is associated not only with overt diabetes but also with the preceding stage known as prediabetes. Diet and pharmacological interventions are the therapeutic approaches to managing prediabetes, but the compliance in combining the two interventions is low. Hence, the efficacy of pharmacological intervention is reduced without diet modification. In our previous study, we established that bredemolic acid (BA) ameliorated glucose homeostasis via increased GLUT 4 expression in the skeletal muscle of prediabetic rats in the absence of diet intervention. However, the effects of bredemolic acid on renal function in prediabetic condition are unknown. Therefore, this study was aimed at investigating the ameliorative effects of bredemolic acid on renal dysfunction in a diet-induced prediabetic rat model. Thirty-six Sprague-Dawley male rats (150–180 g) were divided into two groups: the nonprediabetic (n=6) and prediabetic (n=30) groups which were fed normal diet (ND) and high-fat high-carbohydrate (HFHC) diet, respectively, for 20 weeks. After the 20th week, the prediabetic groups were subdivided into prediabetic control (PD) and 4 other prediabetic groups which were treated with either BA (80 mg/kg) or metformin (MET, 500 mg/kg) for further 12 weeks (21st to 32nd). Plasma, urine, and kidney samples were collected for biochemical analysis. The untreated prediabetic (PD) rats presented increased fluid intake and urine output; increased creatinine, urea, and uric acid plasma concentrations; albuminuria; proteinuria; sodium retention; potassium loss; increased aldosterone and kidney injury molecule (KIM-1) concentration; and increased urinary podocin mRNA expression. However, BA administration attenuated the renal markers and oxidative stress and decreased the urinary podocin mRNA expression. In conclusion, BA administration, regardless of diet modification, attenuates renal dysfunction in an experimentally induced prediabetic state.

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Pharmacology Issues Related to Dementia Syndrome of Depression in Elderly Residents of Long-Term Care Settings

Perspectives on Neurophysiology and Neurogenic Speech and Language Disorders ◽

10.1044/nnsld25.2.61 ◽

2015 ◽

Vol 25 (2) ◽

pp. 61-69

Author(s):

Angel L. Ball ◽

Adina S. Gray

Keyword(s):

Depressive Symptoms ◽

The Elderly ◽

Environmental Communication ◽

Pharmacological Intervention ◽

Team Approach ◽

Discussion Paper ◽

Term Care ◽

Anticholinergic Medications ◽

Inappropriate Treatment ◽

Dementia Syndrome

Pharmacological intervention for depressive symptoms in institutionalized elderly is higher than the population average. Among the patients on such medications are those with a puzzling mix of symptoms, diagnosed as “dementia syndrome of depression,” formerly termed “pseudodementia”. Cognitive-communicative changes, potentially due to medications, complicate the diagnosis even further. This discussion paper reviews the history of the terminology of “pseudodementia,” and examines the pharmacology given as treatment for depressive symptoms in the elderly population that can affect cognition and communication. Clinicians can reduce the risk of misdiagnosis or inappropriate treatment by having an awareness of potential side effects, including decreased attention, memory, and reasoning capacities, particularly due to some anticholinergic medications. A team approach to care should include a cohesive effort directed at caution against over-medication, informed management of polypharmacology, enhancement of environmental/communication supports and quality of life, and recognizing the typical nature of some depressive signs in elderly institutionalized individuals.

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