PubMed Health⌕ Search

Biomedical subjects

L Tecott

Publications and source records attributed to L Tecott.

9 recordsLinked to original sources
PubMed2001

Ethanol hypersensitivity and olfactory discrimination defect in mice lacking a homolog of Drosophila neuralized.

Neurogenic genes in the Notch receptor-mediated signaling pathway play important roles in neuronal cell fate specification as well as neuronal differentiation. The Drosophila neuralized gene is one of the neurogenic genes. We have cloned a mouse homolog of Drosophila neuralized, m-neu1, and found that the m-neu1 transcript is expressed in differentiated neurons. Mice deficient for m-neu1 are viable and morphologically normal, but exhibit specific defects in olfactory discrimination and hypersensitivity to ethanol. These findings reveal an essential role of m-neu1 in ensuring proper processing of certain information in the adult brain.

Amino Acid Sequence↗
PubMed1999

A Huntington's disease CAG expansion at the murine Hdh locus is unstable and associated with behavioural abnormalities in mice.

Huntington's disease (HD) is a dominant disorder characterized by premature and progressive neurodegeneration. In order to generate an accurate model of the disease, we introduced an HD-like mutation (an extended stretch of 72-80 CAG repeats) into the endogenous mouse Hdh gene. Analysis of the mutation in vivo reveals significant levels of germline instability, with expansions, contractions and sex-of-origin effects in evidence. Mice expressing full-length mutant protein display abnormal social behaviour in the absence of acute neurodegeneration. Given that psychiatric changes, including irritability and aggression, are common findings in HD patients, our data are consistent with the hypothesis that some clinical features of HD may be caused by pathological processes that precede gross neuronal cell death. This implies that effective treatment of HD may require an understanding and amelioration of these dysfunctional processes, rather than simply preventing the premature death of neurons in the brain. These mice should facilitate the investigation of the molecular mechanisms that underpin the pathway from genotype to phenotype in HD.

Animals↗
PubMed1999

Transgenic approaches to epilepsy.

Transgenic animal models can reconstruct cellular, biochemical, and molecular alterations associated with human diseases and may help identify key disease mechanisms. Gene disruption, which results in the loss of the functional gene product, is the most common genetic alteration generated by transgenic approaches. Gene disruption can be introduced by random transgene integration or by gene targeting. Both of these approaches have resulted in mice that display recurrent seizures reminiscent of epilepsy. Here, we briefly describe the techniques of random transgene insertion and gene targeting and discuss how these methods were used to generate the epileptic jerky and 5-hydroxytryptamine (5-HT2C) receptor deficient mice. We also analyze how these mutants can contribute to our understanding of the molecular and cellular mechanisms underlying epileptic seizures.

Animals↗
PubMed1996

Open trial of fluvoxamine treatment for combat-related posttraumatic stress disorder.

A 10-week open-label trial of fluvoxamine was conducted for male Vietnam combat veterans with chronic PTSD. Subjects were excluded if they met full current criteria for panic disorder or agoraphobia, and lifetime criteria for psychosis, bipolar disorder, or organic mental syndrome. Repeated MANOVA was performed to determine change over time. Fluvoxamine was well tolerated; side effects were observed primarily early in treatment with headache, insomnia, sedation, and gastrointestinal distress being most frequent. Fluvoxamine was effective for treating the core intrusion, avoidance, and arousal symptoms of PTSD. Large treatment effects were seen by 4-6 weeks, and maintained at 10 weeks. The magnitude of change was greater than has been previously reported for antidepressant treatment of male Vietnam combat veterans with PTSD.

Ambulatory Care↗
PubMed1995

Expression of a serotonin-gated ion channel in embryonic neural and nonneural tissues.

The neurotransmitter serotonin (5HT) has been implicated in morphogenesis of central nervous system and craniofacial structures. The actions of serotonin are mediated by multiple receptor subtypes, one of which, the 5HT3 receptor, is a ligand-gated ion channel. To determine whether this channel may contribute to the proposed morphogenic actions of serotonin, the expression of 5HT3 receptor transcripts was examined during mouse embryogenesis and correlated with the distribution of serotonin transporter mRNA and serotonin immunoreactivity. The pattern of 5HT3 receptor mRNA expression within the brain suggests possible roles for this receptor in the proliferation, differentiation, or migration of CNS neurons. In the peripheral nervous system, 5HT3 receptor transcripts were observed within cranial nerve sensory ganglia, olfactory neuroepithelia, and sympathoadrenal and enteric nervous systems during the initial stages of their formation. Striking expression of 5HT3 receptor transcripts occurred outside the nervous system, in association with regions of active chondrogenesis in the vertebral column, limbs, and craniofacial region, suggesting a possible involvement of this receptor subtype in the morphogenesis of olfactory receptor neurons, teeth, and genitalia.

Animals↗
PubMed1992

Serotonin receptor 1c gene assigned to X chromosome in human (band q24) and mouse (bands D-F4).

In the mammalian nervous system, serotonin (5-hydroxytryptamine) binds to distinct cell surface receptor subtypes that are defined by their ligand binding and effector-coupling properties. The 5HT1c receptor is a G-protein coupled receptor that stimulates phospholipase C-catalyzed hydrolysis of phosphatidylinositol bisphosphate, leading to the mobilization of intracellular calcium and to the activation of protein kinase C. By using somatic cell hybrid analysis and FISH, we have mapped the HTR1C locus to the human X chromosome, band q24 and to the mouse X chromosome region D-F4. Comparison of these map positions offers new insights into the evolution of human and murine X chromosomes. Since HTR1C is expressed in certain parts of the central nervous system and abnormal function of the serotoninergic system has been implicated in affective disorders, obsessive-compulsive disorder and epilepsy, establishing the precise map position of HTR1C is an important first step toward evaluating this locus as a candidate for mutations in these syndromes and in X-linked mental disorders.

Animals↗
PubMed1984

The role of stimulus intensity and stress in opioid-mediated analgesia.

Rats exposed to a Pavlovian conditioning paradigm developed naloxone-reversible analgesia only when the intensity of a noxious unconditioned stimulus was suprathreshold and the level of stress was augmented. The time course of the onset of this conditioned analgesia was reproduced by systemic administration of morphine. These findings suggest that both a minimal level of stimulus intensity and stress are necessary for the activation of endogenous opioid-mediated analgesia.

Analgesia↗
PubMed1984

Pain-induced vocalization in the rat and its modification by pharmacological agents.

Vocalization was induced in rats by electrical stimulation of the tail (pain-induced vocalization), and its components were characterized in terms of latency, duration, frequency spectrum and energy. Noxious stimuli at threshold elicit a single vocalization component (V1). Increases in stimulus intensity produce additional discrete vocalization components (V2-Vn) with successively longer latencies, termed the vocalization afterdischarge (AD). The AD components are acoustically similar to each other but differ significantly from the V1 component. The duration, the specific acoustic measures and the sound energy of both V1 and AD components are positively correlated with intensity of the stimulus. The dependence of the V1 and AD components on the affective state of the rat was evaluated by comparing the acoustic characteristics of both components to those of stress-induced vocalizations, and by studying the effects of the anxiolytic drug diazepam and physical restraint on the threshold of V1 and AD. The AD components were markedly more dependent on the affective state of the rat then was the V1 component. A moderately low dose of morphine (3.0 mg/kg) also preferentially affected the AD component, suggesting that a significant portion of the action of morphine on pain-induced vocalization is mediated through its action on the affective state of the rat.

Animals↗