No phylogeny without ontogeny: a comparative and developmental search for the sources of sleep-like neural and behavioral rhythms.

A comprehensive review is presented of reported aspects and putative mechanisms of sleep-like motility rhythms throughout the animal kingdom. It is proposed that 'rapid eye movement (REM) sleep' be regarded as a special case of a distinct but much broader category of behavior, 'rapid body movement (RBM) sleep', defined by intrinsically-generated and apparently non-purposive movements. Such a classification completes a 2 × 2 matrix defined by the axes sleep versus waking and active versus quiet.

Frameshift proteins in autosomal dominant forms of Alzheimer disease and other tauopathies.

Frameshift (+1) proteins such as APP(+1) and UBB(+1) accumulate in sporadic cases of Alzheimer disease (AD) and in older subjects with Down syndrome (DS). We investigated whether these proteins also accumulate at an early stage of neuropathogenesis in young DS individuals without neuropathology and in early-onset familial forms of AD (FAD), as well as in other tauopathies, such as Pick disease (PiD) or progressive supranuclear palsy (PSP). APP(+1) is present in many neurons and beaded neurites in very young cases of DS, which suggests that it is axonally transported.

The proteasome in Alzheimer's disease and Parkinson's disease: lessons from ubiquitin B+1.

Ubiquitin-containing cellular inclusions are characteristic of major neurodegenerative diseases and suggest an involvement of the ubiquitin-proteasome system. The frameshifted form of ubiquitin has proved to be a valuable tool for studying the role of the ubiquitin-proteasome system. It is an endogenous reporter for proteasome activity in human pathology but it is also capable of inhibiting proteasomal degradation.

Glucocorticoid hormone (cortisol) affects axonal transport in human cortex neurons but shows resistance in Alzheimer's disease.

1 The changes of tissue sensitivity to glucocorticoids are associated with many pathological states including neurological diseases. In the present study, using a novel in vitro post-mortem tracing method on human brain slices, we demonstrated that cortisol, a major glucocorticoid hormone in humans, affected axonal transport both in the cortex neurons in four Alzheimer's disease (AD) patients and four nondemented controls. 2 Cortisol appeared to affect axonal transport of prefrontal cortex (PFC) and temporal cortex (TC) neurons in AD patients and controls in a dose-dependent way at concentrations of 30, 60, 120 and 240 microg dl(-1).

Impaired axonal transport of cortical neurons in Alzheimer's disease is associated with neuropathological changes.

Using a novel in vitro post mortem tracing method, we demonstrate a decrease of axonal transport in the temporal cortex neurons as compared to axonal transport in the prefrontal cortex neurons in AD patients, but not in non-demented controls. The decrease of axonal transport is related to the degree of neuropathological changes, as the temporal cortex undergoes more severe neuropathological changes in AD. The present study provides, for the first time, direct evidence of the presence of impaired axonal transport in AD brains.

Circadian and age-related modulation of thermoreception and temperature regulation: mechanisms and functional implications.

At older ages, the circadian rhythm of body temperature shows a decreased amplitude, an advanced phase, and decreased stability. The present review evaluates to what extent these changes may result from age-related deficiencies at several levels of the thermoregulatory system, including thermoreception, thermogenesis and conservation, heat loss, and central regulation. Whereas some changes are related to the aging process per se, others appear to be secondary to other factors, for which the risk increases with aging, notably a decreased level of fitness and physical activity.

Ectopic adenoviral vector-directed expression of Sema3A in organotypic spinal cord explants inhibits growth of primary sensory afferents.

Sema3A (Sema III, SemD, collapsin-1) can induce neuronal growth cone collapse and axon repulsion of distinct neuronal populations. To study Sema3A function in patterning afferent projections into the developing spinal cord, we employed the recombinant adenoviral vector technique in embryonic rat spinal cord slices. Virus solution was injected in the dorsal aspect of organotypic spinal cord cultures with segmentally attached dorsal root ganglia (sc-DRG).

Priming with interleukin-1beta suppresses experimental allergic encephalomyelitis in the Lewis rat.

Lewis rats exhibit multiple defects in their hypothalamus-pituitary-adrenal (HPA) system that are considered to play a causal role in the susceptibility of this strain to autoimmune diseases, i.e. experimental allergic encephalomyelitis (EAE).

Male-to-female transsexuals have female neuron numbers in a limbic nucleus.

Transsexuals experience themselves as being of the opposite sex, despite having the biological characteristics of one sex. A crucial question resulting from a previous brain study in male-to-female transsexuals was whether the reported difference according to gender identity in the central part of the bed nucleus of the stria terminalis (BSTc) was based on a neuronal difference in the BSTc itself or just a reflection of a difference in vasoactive intestinal polypeptide innervation from the amygdala, which was used as a marker. Therefore, we determined in 42 subjects the number of somatostatin-expressing neurons in the BSTc in relation to sex, sexual orientation, gender identity, and past or present hormonal status.

Decreased vasopressin gene expression in the biological clock of Alzheimer disease patients with and without depression.

Circadian rhythm disturbances are frequently present in Alzheimer disease (AD). In the present study, we investigated the expression of vasopressin (AVP) mRNA in the human suprachiasmatic nucleus (SCN). The in situ hybridization procedure on formalin-fixed paraffin-embedded material was improved to such a degree that we could, for the first time, visualize AVP mRNA expressing neurons in the human SCN and carry out quantitative measurements.

Vasopressin induces a luteinizing hormone surge in ovariectomized, estradiol-treated rats with lesions of the suprachiasmatic nucleus.

The luteinizing hormone surge in the female rat is the result of the integration of multiple signals within the medial preoptic area. The medial preoptic area contains gonadotropin-releasing hormone neurons that are responsible for the release of luteinizing hormone, neurons containing estrogen receptors and terminals originating from the suprachiasmatic nucleus with, for example, vasopressin as neurotransmitter. Both the medial preoptic area and suprachiasmatic nucleus are crucial for the occurrence of luteinizing hormone surges, since lesioning of either nucleus prevents pre-ovulatory and steroid-induced luteinizing hormone surges.

Actigraphic monitoring of movement and rest-activity rhythms in aging, Alzheimer's disease, and Parkinson's disease.

Actigraphy, the long-term assessment of wrist movements, is used in several research fields, among which are included sleep and circadian rhythms. Actigraphs record movements using accelerometers. The present paper addresses some basic problems and their solutions in the actigraphic assessment of movement, motor symptoms, circadian rest-activity rhythms, and nocturnal agitation in healthy elderly and elderly suffering from a neurodegenerative disease (i.

Increased number of corticotropin-releasing hormone expressing neurons in the hypothalamic paraventricular nucleus of patients with multiple sclerosis.

Observations in experimental allergic encephalomyelitis (EAE), a model for multiple sclerosis (MS), have indicated that a low activity of the hypothalamo-pituitary-adrenal (HPA) system is accompanied by a high susceptibility for EAE in rat strains and that elevated corticosteroid levels are necessary for spontaneous recovery from EAE. The HPA axis activity is regulated by both corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP). Both types of neurons are localized in the paraventricular nucleus (PVN) of the hypothalamus.

Activation of mesocortical dopaminergic system in the rat in response to neonatal medial prefrontal cortex lesions. Concurrence with functional sparing.

Neonatal lesions of the medial part of the rat prefrontal cortex (mPFC) (performed at the age of 6 days) resulted in a sparing in the performance of spatial delayed alternation (SDA) and an increase in dopaminergic (DA) innervation. The increased DA innervation was primarily observed in the remaining part of the mPFC. The DA fibre density was considerably higher in the non-ablated part of the mPFC, and the fibres were thicker with more large varicosities compared with sham-operated controls.

Abnormalities in the spontaneous firing patterns of cultured rat neocortical neurons after chronic exposure to picrotoxin during development in vitro.

We have used the GABA-A antagonist picrotoxin (PTX) to investigate whether chronic disinhibition, leading to intensified neuronal firing, would induce a specific pattern of physiological alterations in cultured rat neocortex cells. Overall mean spontaneous discharge rates were little affected by 1 microM PTX but firing occurred mainly as repetitive high-frequency bursts of action potentials. This "phasic" pattern contrasted with the irregular, quasi-random, firing usually seen in control units.

Chronic blockade of bioelectric activity in neonatal rat cortex grown in vitro: morphological effects.

Culture thickness, numerical density of neurons and neuronal survival were studied in timed series of control and tetrodotoxin-silenced neocortical cultures to provide information on the role of bioelectric activity on neuronal development. In control cultures, culture thickness and number of surviving neurons decrease during the first weeks in vitro, but remain constant between 2 and 3 weeks indicating that the cultures are essentially mature. In the 4th week in vitro a further decrease in surviving neurons was observed.

Chronic blockade of bioelectric activity in neonatal rat neocortex in vitro: physiological effects.

We have examined what effect the loss of spontaneous bioelectric activity has on neural network formation in organotypic rat neocortical explants grown under serum-free culture conditions. Explants were taken from dorsal midline (presumptive visual) and lateral (presumptive auditory) occipital cortex and chronically exposed to tetrodotoxin which blocked all measurable bioelectric activity between change of medium. Extracellular recordings revealed complex, rhythmic spontaneous and evoked multiunit discharges in all explants examined (following tetrodotoxin washout in the experimental group).

Alterations in the circadian rest-activity rhythm in aging and Alzheimer's disease.

The suprachiasmatic nucleus, considered to be the endogenous circadian clock in the mammalian brain, shows morphological changes with aging, which become even more pronounced in Alzheimer's disease (AD). In order to assess possible functional implications of these alterations, circadian rest-activity rhythms of 6 young and 13 old volunteers and of 12 AD patients were studied with a recently developed ambulatory rest-activity monitor (RA24). Young and old volunteers showed no differences in their rest-activity rhythm in any of the variables studied.

Role of noradrenaline in behavioral changes after defeat in male and female rats.

We have tested the effect of noradrenaline depletion by clonidine in agonistic behavior of intact male and gonadectomized testosterone-treated female rats. Animals were subjected to the 'resident-intruder' paradigm: in 4 consecutive daily confrontations residents defeated intruders. Clonidine-treated intruder males showed higher levels of aggression than did their saline-injected controls.

Electrophysiological properties of neurons in neonatal rat occipital cortex slices grown in a serum-free medium.

The electrophysiological properties of individual neurons within organotypic explants of neonatal rat cortex were examined via intracellular recordings. The explants were grown for two weeks in a serum-free medium. The electrophysiological properties of the neurons within these explants were similar to those reported for both adult cortex in vivo and short-term in vitro slice preparations.

The use of fetal mouse spinal cord-dorsal root ganglion explants to study the factors underlying selective connections in vitro.

Dorsal root ganglion (DRG) afferents selectively project to dorsal spinal cord (SC) explants when grown in a medium containing serum or a serum-free medium (CDM) containing galactose compounds. SC-DRG explants grown in CDM retain their gross morphological characteristics over several months in vitro, greatly facilitating the mapping of the sensory afferents within given regions of the cord explant. Explants grown in CDM without the addition of galactose show no such selective preference for dorsal cord, and terminate equally throughout the cord.