Effect of Pharmaceutical Intervention in Pharmacologically Treated Hypertensive Patients-A Cluster-Randomized Clinical Trial: AFPRES-CLM Study.

Background: Evaluate the effect of a community pharmaceutical intervention on the control of blood pressure in hypertensive patients treated pharmacologically.

Methods: A cluster-randomized clinical trial of 6 months was carried out. It was conducted in the Autonomous Community of Castilla-La Mancha (Spain).

Morphine-withdrawal aversive memories and their extinction modulate H4K5 acetylation and Brd4 activation in the rat hippocampus and basolateral amygdala.

Chromatin modification is a crucial mechanism in several important phenomena in the brain, including drug addiction. Persistence of drug craving and risk of relapse could be attributed to drug-induced epigenetic mechanisms that seem to be candidates explaining long-lasting drug-induced behaviour and molecular alterations. Histone acetylation has been proposed to regulate drug-seeking behaviours and the extinction of rewarding memory of drug taking.

Molecular Mechanisms Underlying the Retrieval and Extinction of Morphine Withdrawal-Associated Memories in the Basolateral Amygdala and Dentate Gyrus.

Despite their indisputable efficacy for pain management, opiate prescriptions remain highly controversial partially due to their elevated addictive potential. Relapse in drug use is one of the principal problems for addiction treatment, with drug-associated memories being among its main triggers. Consequently, the extinction of these memories has been proposed as a useful therapeutic tool.

Distinct Regulation of Dopamine D3 Receptor in the Basolateral Amygdala and Dentate Gyrus during the Reinstatement of Cocaine CPP Induced by Drug Priming and Social Stress.

Relapse in the seeking and intake of cocaine is one of the main challenges when treating its addiction. Among the triggering factors for the recurrence of cocaine use are the re-exposure to the drug and stressful events. Cocaine relapse engages the activity of memory-related nuclei, such as the basolateral amygdala (BLA) and the hippocampal dentate gyrus (DG), which are responsible for emotional and episodic memories.

Unraveling the molecular mechanisms involved in alcohol intake and withdrawal in adolescent mice exposed to alcohol during early life stages.

Alcohol interferes with foetal development and prenatal alcohol exposure can lead to adverse effects known as foetal alcohol spectrum disorders. We aimed to assess the underlying neurobiological mechanisms involved in alcohol intake and withdrawal in adolescent mice exposed to alcohol during early life stages, in discrete brain areas. Pregnant C57BL/6 female mice were exposed to binge alcohol drinking from gestation to weaning.

Correction to: Gel electrophoresis of human sperm: a simple method for evaluating sperm protein quality.

[This corrects the article DOI: 10.1186/s12610-018-0076-0.].

Gel electrophoresis of human sperm: a simple method for evaluating sperm protein quality.

Background: The limitations of conventional sperm analyses have highlighted the need for additional means of evaluating sperm quality.

Methods: In a study of a cohort of 245 men with known conventional sperm parameters, one-dimensional PAGE was used to monitor protein content and quality in samples from individual ejaculates.

Results: The sperm protein content varied markedly from sample to another, especially in the high-molecular-weight range.

Defining the human sperm microtubulome: an integrated genomics approach.

Sperm motility notably depends on the structural integrity of the flagellum and the regulation of microtubule dynamics. Although researchers have started to use "omics" techniques to characterize the human sperm's molecular landscape, the constituents responsible for the assembly, organization, and dynamics of the flagellum microtubule have yet to be fully defined. In this study, we defined a core set of 116 gene products associated with the human sperm microtubulome (including products potentially involved in abnormal ciliary phenotypes and male infertility disorders).

Two-Dimensional Electrophoresis Protocols to Analyze the Microtubule-Associated Tau Proteins from Several Biological Sources.

Technology breakthrough in proteomics enables to gather qualitative and quantitative information about a protein or a complex mixture of proteins. Two-dimensional gel electrophoresis remains an interesting technique, which provides an overview of the complexity of isovariants from a single protein when coupled to western blotting. Here, we describe a detailed protocol for the two-dimensional analysis of microtubule-associated Tau isovariants from cell to human or mouse brain tissue.

Reduced Tau protein expression is associated with frontotemporal degeneration with progranulin mutation.

Reduction of Tau protein expression was described in 2003 by Zhukareva et al. in a variant of frontotemporal lobar degeneration (FTLD) referred to as diagnosis of dementia lacking distinctive histopathology, then re-classified as FTLD with ubiquitin inclusions. However, the analysis of Tau expression in FTLD has not been reconsidered since then.

miR-132/212 deficiency impairs tau metabolism and promotes pathological aggregation in vivo.

Alzheimer's disease (AD) and related tauopathies comprise a large group of neurodegenerative diseases associated with the pathological aggregation of tau protein. While much effort has focused on understanding the function of tau, little is known about the endogenous mechanisms regulating tau metabolism in vivo and how these contribute to disease. Previously, we have shown that the microRNA (miRNA) cluster miR-132/212 is downregulated in tauopathies such as AD.

Cholesterol 24-hydroxylase defect is implicated in memory impairments associated with Alzheimer-like Tau pathology.

Alzheimer's disease (AD) is characterized by both amyloid and Tau pathologies. The amyloid component and altered cholesterol metabolism are closely linked, but the relationship between Tau pathology and cholesterol is currently unclear. Brain cholesterol is synthesized in situ and cannot cross the blood-brain barrier: to be exported from the central nervous system into the blood circuit, excess cholesterol must be converted to 24S-hydroxycholesterol by the cholesterol 24-hydroxylase encoded by the CYP46A1 gene.

MBNL Sequestration by Toxic RNAs and RNA Misprocessing in the Myotonic Dystrophy Brain.

For some neurological disorders, disease is primarily RNA mediated due to expression of non-coding microsatellite expansion RNAs (RNA(exp)). Toxicity is thought to result from enhanced binding of proteins to these expansions and depletion from their normal cellular targets. However, experimental evidence for this sequestration model is lacking.

Role of the Tau N-terminal region in microtubule stabilization revealed by new endogenous truncated forms.

Tau is a central player in Alzheimer's disease (AD) and related Tauopathies, where it is found as aggregates in degenerating neurons. Abnormal post-translational modifications, such as truncation, are likely involved in the pathological process. A major step forward in understanding the role of Tau truncation would be to identify the precise cleavage sites of the several truncated Tau fragments that are observed until now in AD brains, especially those truncated at the N-terminus, which are less characterized than those truncated at the C-terminus.

Consensus brain-derived protein, extraction protocol for the study of human and murine brain proteome using both 2D-DIGE and mini 2DE immunoblotting.

Two-dimensional gel electrophoresis (2DE) is a powerful tool to uncover proteome modifications potentially related to different physiological or pathological conditions. Basically, this technique is based on the separation of proteins according to their isoelectric point in a first step, and secondly according to their molecular weights by SDS polyacrylamide gel electrophoresis (SDS-PAGE). In this report an optimized sample preparation protocol for little amount of human post-mortem and mouse brain tissue is described.

Brain pathology in myotonic dystrophy: when tauopathy meets spliceopathy and RNAopathy.

Myotonic dystrophy (DM) of type 1 and 2 (DM1 and DM2) are inherited autosomal dominant diseases caused by dynamic and unstable expanded microsatellite sequences (CTG and CCTG, respectively) in the non-coding regions of the genes DMPK and ZNF9, respectively. These mutations result in the intranuclear accumulation of mutated transcripts and the mis-splicing of numerous transcripts. This so-called RNA gain of toxic function is the main feature of an emerging group of pathologies known as RNAopathies.

Detrimental effects of diet-induced obesity on τ pathology are independent of insulin resistance in τ transgenic mice.

The τ pathology found in Alzheimer disease (AD) is crucial in cognitive decline. Midlife development of obesity, a major risk factor of insulin resistance and type 2 diabetes, increases the risk of dementia and AD later in life. The impact of obesity on AD risk has been suggested to be related to central insulin resistance, secondary to peripheral insulin resistance.

Clinical, neuropathological, and biochemical characterization of the novel tau mutation P332S.

MAPT mutations cause autosomal dominant frontotemporal lobar degeneration. These diseases are characterized by considerable heterogeneity in their clinical, neuropathological, and biochemical presentations. We describe the full characterization of a family with autosomal dominant frontotemporal lobar degeneration caused by a novel MAPT mutation.

Tau phosphorylation and sevoflurane anesthesia: an association to postoperative cognitive impairment.

Background: There is a growing interest in the involvement of anesthetic agents in the etiology of postoperative cognitive dysfunction. Recent animal studies suggest that acute anesthesia induces transient hyperphosphorylation of tau, an effect essentially ascribed to hypothermia. The main aim of the present study was to investigate effects, in normothermic conditions, of acute or repeated exposure to sevoflurane, a halogenated anesthetic agent, on hippocampal tau phosphorylation and spatial memory in adult mice.

Beneficial effects of exercise in a transgenic mouse model of Alzheimer's disease-like Tau pathology.

Tau pathology is encountered in many neurodegenerative disorders known as tauopathies, including Alzheimer's disease. Physical activity is a lifestyle factor affecting processes crucial for memory and synaptic plasticity. Whether long-term voluntary exercise has an impact on Tau pathology and its pathophysiological consequences is currently unknown.

Analysis of exonic regions involved in nuclear localization, splicing activity, and dimerization of Muscleblind-like-1 isoforms.

Muscleblind-like-1 (MBNL1) is a splicing regulatory factor controlling the fetal-to-adult alternative splicing transitions during vertebrate muscle development. Its capture by nuclear CUG expansions is one major cause for type 1 myotonic dystrophy (DM1). Alternative splicing produces MBNL1 isoforms that differ by the presence or absence of the exonic regions 3, 5, and 7.

Cholinesterase activity in brain of senescence-accelerated-resistant mouse SAMR1 and its variation in brain of senescence-accelerated-prone mouse SAMP8.

The early-onset, irreversible, severe deficits of learning and memory in the senescence-accelerated mouse (SAM)-prone/8 (SAMP8) support its use as an animal model for human dementias of early onset. Possible implication of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in cognitive dysfunction of SAMP8 mice was studied by comparing cholinesterase (ChE) expression in brains of SAMP8 mice and of their normal control, SAM-resistant/1 (SAMR1) mice. The level of ChE mRNAs was the same in SAMP8 and SAMR1 brains, which agreed with their equal AChE activity (3.

The level of butyrylcholinesterase activity increases and the content of the mRNA remains unaffected in brain of senescence-accelerated mouse SAMP8.

Looking at cholinesterases (ChEs) changes in age-related mental impairment, the expression of ChEs in brain of senescence accelerated-resistant (SAMR1) and senescence accelerated-prone (SAMP8) mice was studied. Acetylcholinesterase (AChE) activity was unmodified and BuChE activity increased twofold in SAMP8 brain. SAMR1 brain contained many AChE-T mRNAs, less BuChE and PRiMA mRNAs and scant AChE-R and AChE-H mRNAs.