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1.
Neuroscience ; 115(1): 285-94, 2002.
Article in English | MEDLINE | ID: mdl-12401341

ABSTRACT

The ventrolateral preoptic nucleus (VLPO) is a group of sleep-active neurons that has been identified in the hypothalamus of rats and is thought to inhibit the major ascending monoaminergic arousal systems during sleep; lesions of the VLPO cause insomnia. Identification of the VLPO in other species has been complicated by the lack of a marker for this cell population, other than the expression of Fos during sleep. We now report that a high percentage of the sleep-active (Fos-expressing) VLPO neurons express mRNA for the inhibitory neuropeptide, galanin, in nocturnal rodents (mice and rats), diurnal rodents (degus), and cats. A homologous (i.e. galanin mRNA-containing cell group) is clearly distinguishable in the ventrolateral region of the preoptic area in diurnal and nocturnal monkeys, as well as in humans. Galanin expression may serve to identify sleep-active neurons in the ventrolateral preoptic area of the mammalian brain. The VLPO appears to be a critical component of sleep circuitry across multiple species, and we hypothesize that shrinkage of the VLPO with advancing age may explain sleep deficits in elderly humans.


Subject(s)
Galanin/physiology , Neurons/metabolism , Preoptic Area/metabolism , Sleep/physiology , Ventromedial Hypothalamic Nucleus/metabolism , Adult , Animals , Aotidae , Cats , Galanin/analysis , Galanin/biosynthesis , Humans , Macaca mulatta , Mice , Neurons/chemistry , Preoptic Area/chemistry , Proto-Oncogene Proteins c-fos/analysis , Proto-Oncogene Proteins c-fos/biosynthesis , RNA, Messenger/analysis , RNA, Messenger/biosynthesis , Rats , Rodentia , Ventral Thalamic Nuclei , Ventromedial Hypothalamic Nucleus/chemistry
2.
Novartis Found Symp ; 231: 242-62; discussion 262-9, 302-6, 2000.
Article in English | MEDLINE | ID: mdl-11131542

ABSTRACT

In recent years, it has become evident that the developing and even the adult mammalian CNS contain a population of undifferentiated, multipotent cell precursors, neural stem cells, the plastic properties of which might be of advantage for the design of more effective therapies for many neurological diseases. This article reviews the recent progress in establishing rodent and human clonal neural stem cell lines, their biological properties, and how these cells can be utilized to correct a variety of defects, with prospects for the near future to harness their behaviour for neural stem cell-based treatment of diseases in humans.


Subject(s)
Central Nervous System/surgery , Genetic Therapy/methods , Neurodegenerative Diseases/surgery , Neurodegenerative Diseases/therapy , Neurons/transplantation , Stem Cell Transplantation , Adult , Animals , Cell Line , Humans
3.
J Cardiopulm Rehabil ; 19(2): 91-7, 1999.
Article in English | MEDLINE | ID: mdl-10200914

ABSTRACT

PURPOSE: The underlying pathophysiology contributing to coronary heart disease also predisposes patients to cerebrovascular disease and associated cognitive disorders. Although prior studies have focused on the neuropsychological sequelae of specific cardiac problems, few have examined the associated cognitive capacities and limitations of typical cardiac patients. The current study was designed to examine neuropsychological functioning among a sample of cardiac rehabilitation (CR) patients. METHODS: Using neuropsychological instruments, patients were compared in a CR program to age-matched outpatient control subjects who had no known history of cardiac or neurologic disease. Cardiac rehabilitation patients were then divided into dichotomous subgroups based on whether they had undergone coronary artery bypass grafting, had experienced a myocardial infarction, had hypertension, or had impaired ejection fraction. Neuropsychological functioning was examined relative to each of these factors. RESULTS: Cardiac rehabilitation patients had poorer neuropsychological test performance than did control subjects, with subtle relative deficits on measures of response generation, memory, and verbal abstraction, and particularly verbal fluency. Low ejection fraction, hypertension, and prior coronary artery bypass graft were associated with greater relative neuropsychological impairments. CONCLUSIONS: Although CR patients were not grossly neuropsychologically impaired as a group, it appears highly likely that many within a given program exhibit some degree of neuropsychological dysfunction. Including neuropsychological screening as part of pre-CR testing would help to identify such patients. This information may help staff to impart health care information in a manner that is most effective for the individual patient and may also be useful in the formation of realistic goals.


Subject(s)
Cognition Disorders/etiology , Coronary Disease/rehabilitation , Neuropsychological Tests , Aged , Analysis of Variance , Angioplasty, Balloon, Coronary , Cognition Disorders/diagnosis , Coronary Artery Bypass , Coronary Disease/complications , Coronary Disease/therapy , Female , Humans , Logistic Models , Male , Mental Status Schedule , Middle Aged , Multivariate Analysis , Quality of Life , Risk Factors , Stroke Volume , Time Factors
4.
Neurobiol Aging ; 19(3): 201-4, 1998.
Article in English | MEDLINE | ID: mdl-9661994

ABSTRACT

Alzheimer's disease (AD) brains display intense microglial immunoreactivity in the area of senile plaques, suggesting that amyloid beta-protein may stimulate microglial infiltration. The activated microglia may modulate an immune response in the brain. Non-steroidal anti-inflammatory drugs (NSAIDs) are candidate therapeutics for AD because their effects on immune system components may influence the course of the disease. The present study examined the effects of an NSAID (indomethacin) on amyloid beta-protein-induced microglial infiltration. Amyloid beta-protein was chronically infused into rat lateral ventricles for 2 weeks. Extracellular amyloid beta-protein deposited along the lining and diffused into the tissue surrounding the lateral ventricle. Immunocytochemical staining showed that animals receiving amyloid beta-protein exhibited dramatic microglial response when compared to vehicle-infused rats. Activated microglia surrounded immunopositive amyloid beta-protein deposits, but this response was significantly attenuated in animals receiving either concurrent i.c.v. or subcutaneous (s.c.) treatment with indomethacin. These results suggest that chronic amyloid beta-protein infusion induces the proliferation of activated microglia and that indomethacin may be an effective treatment for inhibiting microglial proliferation.


Subject(s)
Amyloid beta-Peptides/antagonists & inhibitors , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Indomethacin/pharmacology , Microglia/drug effects , Amyloid beta-Peptides/pharmacology , Animals , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Brain/pathology , Brain Chemistry/drug effects , Immunohistochemistry , Indomethacin/administration & dosage , Injections, Intraventricular , Male , Rats
5.
J Biol Rhythms ; 12(3): 278-89, 1997 Jun.
Article in English | MEDLINE | ID: mdl-9181439

ABSTRACT

The "long nights" protocol was designed to evaluate sleep processes and circadian rhythm parameters in young humans. A total of 19 children (10 boys, ages 11.2 to 14.1 years [mean = 12.7 +/- 1.0], and 9 girls, ages 12.2 to 14.4 years [mean = 13.1 +/- 0.7]) took part in the study. Sleep/wake initially was assessed at home using actigraphy and diary for 1 week on each child's self-selected schedule followed by an 8-night fixed light-dark (LD) condition, while sleeping from 22:00 to 08:00 h and wearing an eye mask to exclude as much light as possible. Phase measurements included 4-night mean actigraphically estimated sleep onset and offset as well as 1-night dim light salivary melatonin onset (DLSMO) phase at the end of each condition. Subjects then lived in the laboratory for 6 consecutive cycles: Day 1 LD = 14:10 h, lights out 22:00 to 08:00 h; Days 2-4 LD = 6:18 h, lights out 18:00 to 12:00 h; Days 5-6 = constant routine in continuous dim light (about 20 lux); Night 6 = 14 h recovery sleep. Phase markers (sleep onset, sleep offset, DLSMO) were significantly less dispersed after the fixed LD as compared to the self-selected condition, indicating efficacy of the LD protocol. Phase markers were correlated at the self-selected assessment (sleep onset vs. sleep offset r = .72; DLSMO vs. sleep onset r = .82; DLSMO vs. sleep offset r = .76) but not on the fixed schedule, probably due to restricted range. The constant routine provided additional phase markers, melatonin offset and midphase. Offset phase of melatonin secretion was significantly correlated with age (r = .62) and Tanner stage (r = .62). In conclusion, these preliminary data indicate a relationship between adolescent development and circadian phase. Thus, the long nights protocol is a feasible way in which to assess circadian parameters in young humans as well as to examine intrinsic sleep processes.


Subject(s)
Circadian Rhythm , Sleep/physiology , Adolescent , Child , Child Development/physiology , Child, Preschool , Humans
6.
Physiol Behav ; 60(5): 1205-8, 1996 Nov.
Article in English | MEDLINE | ID: mdl-8916172

ABSTRACT

Aged rats often display abnormal circadian activity rhythms; the rhythm amplitude is low and entrainment to light-dark cycles is irregular. The activity rhythm of young rats can be entrained by both light and nonphotic cues, specifically food availability. In young rats, entrainment to restricted feeding cycles does not depend on intact suprachiasmatic nuclei, the presumed anatomical location of the light-entrainable oscillator. In this study, aged rats that displayed disrupted entrainment to light were assessed for their ability to entrain to restricted feeding schedules. Aged rats, young controls, and young suprachiasmatic nuclei-lesioned (SCN) rats were placed on a food restriction schedule (FR) for 14 days. Food was available for 2 h during the light phase of a 12-h light-dark cycle. Despite the absence of entrainment to light/dark cycles, both SCN-lesioned and aged groups showed entrainment to FR, with clear bouts of anticipatory activity during a period of complete food deprivation following 2 weeks of FR. The results suggest that the dysrhythmia of aged rats is a result of natural deterioration of a central circadian light-entrainable pacemaker, but that a secondary oscillator entrainable to food cycles is spared.


Subject(s)
Aging/physiology , Circadian Rhythm/physiology , Food Deprivation/physiology , Animals , Female , Rats , Rats, Sprague-Dawley , Suprachiasmatic Nucleus/physiology
7.
Scanning Microsc ; 8(2): 325-35; discussion 335-6, 1994.
Article in English | MEDLINE | ID: mdl-7535473

ABSTRACT

The amyloid precursor protein (APP) is an integral membrane component of eukaryotic cells. A variety of research approaches have addressed the contribution of the beta amyloid peptide region of the APP to neuritic plaque structure and formation in the Alzheimer disease brain as well as the relationship between beta amyloid accumulation and the occurrence of dementia. However, there is limited information available concerning the cellular consequences of amyloid deposition. The present studies were undertaken to investigate the relationship between beta amyloid and intercellular junctions. Transfected PC12 cell lines, that overexpress the beta amyloid peptide, exhibit structural and functional alterations at the cell surface and tend to form aggregates more readily than normal control cells. Intermediate junctions were the most common intercellular interactions of both normal and transfected cells. However, the control and transfected cells differed since areas of continuous and extensive junctions were readily seen in transfected cells and infrequently seen in control cells. The data suggest that excess accumulation of beta amyloid is associated with the junctional apparatus and may be related to increased intercellular adhesion.


Subject(s)
Amyloid beta-Peptides/metabolism , Actins/metabolism , Amyloid beta-Peptides/immunology , Animals , Cell Membrane/ultrastructure , Epitopes , Immunohistochemistry , Intercellular Junctions/ultrastructure , Microscopy, Electron , PC12 Cells , Rats , Staining and Labeling , Tissue Distribution , Transfection
8.
Brain Res ; 621(1): 145-9, 1993 Sep 03.
Article in English | MEDLINE | ID: mdl-8221067

ABSTRACT

Deposition of beta/A4 amyloid in brain is a defining characteristic of Alzheimer disease (AD); however, the extent to which amyloid deposits may interfere with normal cellular processes is incompletely understood. We examined this issue by means of PC12 cells. After transfection with DNA coding for 97 amino acids of the beta/A4 C-terminal region of the amyloid precursor protein, beta/A4 antigen was visible at the cell membrane. We report that normal unstimulated PC12 cells exhibit ruffling activity at the cell surface when plated on a plastic substrate. Relative to control cells, however, those that over-expressed the beta/A4 C-terminal peptide had significantly higher levels of ruffling activity, suggesting a structural and/or functional membrane modification. Similar cellular alterations, if present, in Alzheimer brain cells, may indicate disturbances in membrane-associated functions, including intercellular communication.


Subject(s)
Alzheimer Disease/metabolism , Alzheimer Disease/pathology , Amyloid beta-Peptides/biosynthesis , Cell Membrane/ultrastructure , Nerve Tissue Proteins/biosynthesis , Animals , Cell Membrane/physiology , PC12 Cells/metabolism
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