doxycycline and memory

LESSONS LEARNED: Staphylococcus aureus infection in cutaneous T-cell lymphoma (CTCL) is thought to contribute to disease progression; thus, adjunctive treatment with antibiotics warrants further investigation. This trial of antibiotic therapy followed by imiquimod in early stage CTCL was not completed because of difficulties with patient accrual. BACKGROUND: Cutaneous T-cell lymphoma (CTCL), a form of non-Hodgkin lymphoma, is a heterogeneous group of malignancies of mature memory T lymphocytes...

Regulation of haematopoietic stem cell fate through conditional gene expression could improve understanding of healthy haematopoietic and leukaemia initiating cell (LIC) biology. We established conditionally immortalised myeloid progenitor cell lines co-expressing constitutive Hoxa9.EGFP and inducible Meis1.dTomato (H9M-ciMP) to study growth behaviour, immunophenotype and morphology under different cytokine/microenvironmental conditions ex vivo upon doxycycline (DOX) induction or removal. The vector design and drug-dependent selection approach identified new retroviral insertion (RVI) sites that potentially collaborate with Meis1/Hoxa9 and define H9M-ciMP fate...

Immune-inflammatory mechanisms are involved in the pathophysiology of bipolar disorder. Tetracyclines present neuroprotective actions based on their anti-inflammatory and microglia suppressant effects. Doxycycline (DOXY) is a tetracycline that demonstrates a better usage profile with protective actions against inflammation and CNS injury. Here, we investigated the effects of DOXY against behavioral, neuroinflammatory, and pro-oxidative changes induced by the d-amphetamine mania model. Adult mice were given d-amphetamine 2...

INTRODUCTION: After the 1990 to 1991 conflict in the Persian Gulf, many Gulf War Veterans began reporting numerous unexplained symptoms including, but not limited to, systemic pain, fatigue, flu-like symptoms, and difficulty with memory/concentration. These symptom clusters are now referred to as Gulf War Illness (GWI). Although the etiology of GWI is still debated, as many as 250,000 former service members have been continually suffering from GWI since 1991, making the need for treatment urgent...

Spatial memory performance declines in both normal aging and Alzheimer's disease. This cognitive deficit is related to hippocampus dysfunction. Gene therapy using neurotrophic factors like Glial cell line-derived neurotrophic factor (GDNF) emerges as a promising approach to ameliorate age-related cognitive deficits. We constructed a two vector regulatable system (2VRS) which consists of a recombinant adenoviral vector (RAd) harboring a Tet-Off bidirectional promoter flanked by GDNF and Green Fluorescent Protein (GFP) genes...

Primary Objective The primary objective of this study was to explore the pharmacological potential of tocopherol and doxycycline against traumatic brain injury-induced cognitive/motor impairment in rats. Research Design Weight drop model of traumatic brain injury. Methods and Procedures After TBI, the animals were treated with doxycycline (50 and 100 mg/kg; p.o), tocopherol (5 and 10 mg/kg; p.o) alone and in combination as doxycycline and tocopherol (50 and 10 mg/kg; p.o) from 1st day to 28th day. The behavioral parameters were performed on a weekly basis from 1st day to 28th day...

Dopaminergic neurotransmission is considered to play an important role not only in reward-based learning, but also in aversive learning. Here, we investigated the role of dopaminergic neurotransmission via dopamine D1 receptors (D1Rs) in aversive memory formation in a passive avoidance test using D1R knockdown (KD) mice, in which the expression of D1Rs can conditionally and reversibly be controlled by doxycycline (Dox) treatment. We also performed whole-brain imaging after aversive footshock stimulation in activity-regulated cytoskeleton protein (Arc)-dVenus D1RKD mice, which were crossbred from Arc-dVenus transgenic mice and D1RKD mice, to examine the distribution of Arc-controlled dVenus expression in the hippocampus and cerebral cortex during aversive memory formation...

BACKGROUND: Increased rates of Staphylococcus aureus resistance and its morbidity and mortality have raised concern about the strategy of antibiotic use. OBJECTIVES: This study aimed to determine the prevalence of methicillin-resistant S. aureus (MRSA) and vancomycin-resistant S. aureus (VRSA) isolates among Thai patients with S. aureus infection and to identify risk factors and appropriate antibiotics for these resistant strains. METHODS: Data of culture-proven S...

Amyotrophic lateral sclerosis is a rapidly progressing and fatal disease characterized by muscular atrophy due to loss of upper and lower motor neurons. Pathogenic mutations in the TARDBP gene encoding TAR DNA binding protein-43 (TDP-43) have been identified in familial amyotrophic lateral sclerosis. We have previously reported transgenic mice with neuronal expression of human TDP-43 carrying the pathogenic A315T mutation (iTDP-43A315T mice) using a tetracycline-controlled inducible promotor system. Constitutive expression of transgenic TDP-43A315T in the absence of doxycycline resulted in pronounced early-onset and progressive neurodegeneration, and motor and memory deficits...

HIV infects the central nervous system and causes HIV/neuroAIDS, which is predominantly manifested in the form of mild cognitive and motor disorder in the era of combination antiretroviral therapy. HIV Tat protein is known to be a major pathogenic factor for HIV/neuroAIDS through a myriad of direct and indirect mechanisms. However, most, if not all of studies involve short-time exposure of recombinant Tat protein in vitro or short-term Tat expression in vivo . In this study, we took advantage of the doxycycline-inducible brain-specific HIV-1 Tat transgenic mouse model, fed the animals for 12 months, and assessed behavioral, pathological, and epigenetic changes in these mice...

Chronic inflammation facilitates tumor progression. We discovered that a subset of non-small cell lung cancer cells underwent a gradually progressing epithelial-to-mesenchymal (EMT) phenotype following a 21-day exposure to IL-1β, an abundant proinflammatory cytokine in the at-risk for lung cancer pulmonary and the lung tumor microenvironments. Pathway analysis of the gene expression profile and in vitro functional studies revealed that the EMT and EMT-associated phenotypes, including enhanced cell invasion, PD-L1 upregulation, and chemoresistance, were sustained in the absence of continuous IL-1β exposure...

BACKGROUND: Postretrieval extinction attenuates the pathological memory associated with psychiatric states such as drug addiction in both humans and rodents. The extinction of a learned response requires gene transcription and protein synthesis after memory retrieval in a time-dependent manner, yet the precise physiological basis after retrieval to allow extinction to neutralize a learned behavior is not fully understood. METHODS: In a cocaine conditioned place preference paradigm, we used a ribosomal tagging strategy to measure the translational state of hippocampal pyramidal neurons after the retrieval of cocaine-associated context memory...

Associative memory can be rendered malleable by a reminder. Blocking the ensuing re-consolidation process is suggested as a therapeutic target for unwanted aversive memories. Matrix metalloproteinase (MMP)-9 is required for structural synapse remodelling involved in memory consolidation. Inhibiting MMP-9 with doxycycline is suggested to attenuate human threat conditioning. Here, we investigate whether MMP-9 inhibition also interferes with threat memory re-consolidation. N=78 male and female human participants learned the association between two visual conditioned stimuli (CS+) and a 50% chance of an unconditioned nociceptive stimulus (US), and between CS- and the absence of US...

Autosomal dominant Alzheimer disease (AD) is caused by rare mutations in one of three specific genes. This is in contrast to idiopathic, late-onset AD (LOAD), which has a more polygenetic risk profile and represents more than 95% of cases. Previously, we have demonstrated that increased expression of microRNA (miRNA)-34a (miR-34a) in AD brain targets genes linked to synaptic plasticity, energy metabolism, and resting state network activity. Here we report the generation of a heterozygous, conditional miR-34a overexpression mouse (miR-34a+/- (TetR-TetO-miR-34a) Transgenic Mice)...

Disruptions in growth hormone/insulin-like growth factor-1 (GH/IGF-1) signaling have been linked to improved longevity in mice and humans. Nevertheless, while IGF-1 levels are associated with increased cancer risk, they have been paradoxically implicated with protection from other age-related conditions, particularly in the brain, suggesting that strategies aimed at selectively increasing central IGF-1 action may have favorable effects on aging. To test this hypothesis, we generated inducible, brain-specific (TRE-IGF-1 × Camk2a-tTA) IGF-1 (bIGF-1) overexpression mice and studied effects on healthspan...

Dysregulation of TAR DNA-binding protein 43 (TDP-43) is a hallmark feature of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), two fatal neurodegenerative diseases. TDP-43 is a ubiquitously expressed RNA-binding protein with many physiological functions, playing a role in multiple aspects of RNA metabolism. We developed transgenic mice conditionally overexpressing human wild-type TDP-43 protein (hTDP-43-WT) in forebrain neurons, a model that recapitulates several key features of FTD. After post-weaning transgene (TG) induction during 1 month, these mice display an early behavioral phenotype, including impaired cognitive and social function with no substantial motor abnormalities...

The IL-7/IL-7R pathway is essential for lymphocyte development and disturbances in the pathway can lead to immune deficiency or T cell mediated destruction. Here, the effect of transient hyperexpression of IL-7 was investigated on immune regulation and allograft rejection under immunosuppression. An experimental in vivo immunosuppressive mouse model of IL-7 hyperexpression was developed using transgenic mice (C57BL/6 background) carrying a tetracycline inducible IL-7 expression cassette, which allowed the temporally controlled induction of IL-7 hyperexpression by Dexamethasone and Doxycycline treatment...

Neurodegenerative diseases (NDs) are a group of chronic, progressive disorders characterized by the gradual loss of neurons that affect specific regions of the brain, which leads to deficits in specific functions (e.g., memory, movement, cognition). The mechanism that drives chronic progression of NDs remains elusive. Among the proposed underlying pathophysiological mechanisms, aggregation and accumulation of misfolded proteins and neuroinflammation have been credited to contribute to extensive neural loss...

OBJECTIVE: To investigate whether longer-term antibiotic treatment improves cognitive performance in patients with persistent symptoms attributed to Lyme borreliosis. METHODS: Data were collected during the Persistent Lyme Empiric Antibiotic Study Europe (PLEASE) trial, a randomized, placebo-controlled study. Study participants passed performance-validity testing (measure for detecting suboptimal effort) and had persistent symptoms attributed to Lyme borreliosis...

The link between blood pressure (BP) and cerebral function is well established. However, it is not clear whether a common mechanism could underlie the relationship between elevated BP and cognitive deficits. The expression of calcyon, a gene abundant in catecholaminergic and hypothalamic nuclei along with other forebrain regions, is increased in the brain of the spontaneously hypertensive rat (SHR) which is a widely accepted animal model of essential hypertension and attention deficit hyperactivity disorder (ADHD)...