Rho proteins and the cellular mechanisms of mental retardation.

The biological basis of mental retardation is poorly understood. Mental retardation is associated with an immature morphology of synaptic spines, structures involved in neurotransmission and memory processes, suggesting that mental retardation is due to a deficiency in neuronal network formation. Recently, several genes involved in X-linked mental retardation (MRX) have been cloned.

Dopamine and noradrenaline efflux in the prefrontal cortex in the light and dark period: effects of novelty and handling and comparison to the nucleus accumbens.

We used on-line microdialysis measurements of dopamine and noradrenaline extracellular concentrations in the medial prefrontal cortex of awake, freely moving rats during the dark and the light period of the day to study whether (i) basal efflux would be higher in the active, dark period than in the inactive, light period; (ii) the activation induced by environmental stimuli would be dependent on these conditions. When determined one day after cannula placement, noradrenaline and dopamine levels were higher during the dark. Maximal relative increases induced by novelty and handling were 150% and 175-200%, respectively, and were very similar in the light and the dark, but the net increases were higher in the dark.

Functional connections between the suprachiasmatic nucleus and the thyroid gland as revealed by lesioning and viral tracing techniques in the rat.

Frequent blood sampling via intraatrial cannula revealed daily rhythms of TSH and thyroid hormones in both male and female Wistar rats. Thermic ablation of the biological clock, i.e.

Differential expression of estrogen receptor alpha and beta immunoreactivity in the human supraoptic nucleus in relation to sex and aging.

The dorsolateral supraoptic nucleus (dl-SON) is the main production site of plasma arginine vasopressin (AVP). Plasma AVP levels and the activity of AVP neurons in humans are higher in males than in premenopausal females. On the other hand, an increased activity of AVP neurons becomes prominent in postmenopausal women who have strongly decreased estrogen levels.

Melatonin sees the light: blocking GABA-ergic transmission in the paraventricular nucleus induces daytime secretion of melatonin.

Despite a pronounced inhibitory effect of light on pineal melatonin synthesis, usually the daily melatonin rhythm is not a passive response to the surrounding world. In mammals, and almost every other vertebrate species studied so far, the melatonin rhythm is coupled to an endogenous pacemaker, i.e.

Sex differences in the distribution of androgen receptors in the human hypothalamus.

The present study reports for the first time the distribution of androgen receptor immunoreactivity (AR-ir) in the human hypothalamus of ten human subjects (five men and five women) ranging in age between 20 years and 39 years using the antibody PG21. Prolonged postmortem delay (72:00 hours) or fixation time (100 days) did not influence the AR-ir. In men, intense nuclear AR-ir was found in neurons of the horizontal limb of the diagonal band of Broca, in neurons of the lateromamillary nucleus (LMN), and in the medial mamillary nucleus (MMN).

The suprachiasmatic nucleus and the circadian time-keeping system revisited.

Many physiological and behavioral processes show circadian rhythms which are generated by an internal time-keeping system, the biological clock. In rodents, evidence from a variety of studies has shown the suprachiasmatic nucleus (SCN) to be the site of the master pacemaker controlling circadian rhythms. The clock of the SCN oscillates with a near 24-h period but is entrained to solar day/night rhythm by light.

Development of nerve connections under the control of neurotrophic factors: parallels with consumer-resource systems in population biology.

The development of connections between neurons and their target cells involves competition between axons for target-derived neurotrophic factors. Although the notion of competition is commonly used in neurobiology, the process is not well understood, and only a few formal models exist. In population biology, in contrast, the concept of competition is well developed and has been studied by means of many formal models of consumer-resource systems.

Molecular misreading in non-neuronal cells.

+1 Frame-shifted proteins such as amyloid precursor protein(+1) and ubiquitin-B(+1) have been identified in the neuropathological hallmarks of Alzheimer's disease. These frameshifts are caused by dinucleotide deletions in GAGAG motifs of messenger RNA encoded by genes that have maintained the unchanged wild-type DNA sequence. This process is termed 'molecular misreading'.

Molecular misreading. A new type of transcript mutation in gerontology.

Molecular misreading is a novel process that causes mutations in neuronal transcripts. It is defined as the inaccurate conversion of genomic information from DNA into nonsense transcripts and the subsequent translation into mutant proteins. As a result of dinucleotide deletions (delta GA, delta GU, delta CU) in and around GAGAG motifs in mRNA the reading frame shifts to the +1 frame, and subsequently the so-called +1 proteins are synthetized.

Polysynaptic neural pathways between the hypothalamus, including the suprachiasmatic nucleus, and the liver.

The suprachiasmatic nucleus of the hypothalamus is responsible for a 24-h rhythm in basal glucose levels in the rat. The neural pathways used by the suprachiasmatic nucleus to mediate this rhythm in plasma glucose have not yet been identified. In the present study we examined whether there are any connections between hypothalamic centers, including the suprachiasmatic nucleus, and the liver, which is the main site for glucose production and storage.

Intercostal nerve implants transduced with an adenoviral vector encoding neurotrophin-3 promote regrowth of injured rat corticospinal tract fibers and improve hindlimb function.

Following injury to central nervous tissues, damaged neurons are unable to regenerate their axons spontaneously. Implantation of peripheral nerves into the CNS, however, does result in axonal regeneration into these transplants and is one of the most powerful strategies to promote CNS regeneration. In the present study implantation of peripheral nerve bridges following dorsal hemisection is combined with ex vivo gene transfer with adenoviral vectors encoding neurotrophin-3 (Ad-NT-3) to examine whether this would stimulate regeneration of one of the long descending tracts of the spinal cord, the corticospinal tract (CST), into and beyond the peripheral nerve implant.

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.

More than a marker: interaction between the circadian regulation of temperature and sleep, age-related changes, and treatment possibilities.

The neurobiological mechanisms of both sleep and circadian regulation have been unraveled partly in the last decades. A network of brain structures, rather than a single locus, is involved in arousal state regulation, whereas the suprachiasmatic nucleus (SCN) has been recognized as a key structure for the regulation of circadian rhythms. Although most models of sleep regulation include a circadian component, the actual mechanism by which the circadian timing system promotes--in addition to homeostatic pressure--transitions between sleep and wakefulness remains to be elucidated.

The human circadian clock and aging.

The suprachiasmatic nucleus (SCN) of the hypothalamus is implicated in the timing of a wide variety of circadian processes. Since the environmental light-dark cycle is the main zeitgeber for many of the rhythms, photic information may have a synchronizing effect on the endogenous clock of the SCN by inducing periodic changes in the biological activity of certain groups of neurons. By studying the brains obtained at autopsy of human subjects, marked diurnal oscillations were observed in the neuropeptide content of the SCN.

Circadian rhythms and sleep in human aging.

This issue of Chronobiology International is dedicated to the age-related changes in circadian rhythms as they occur in humans. It seems timely to give an overview of the knowledge and hypotheses on these changes now that we enter a century in which the number and percentage of elderly in the population will be unprecedented. Although we should take care not to follow the current tendency to think of old age as a disease--ignoring the fine aspects of being old--there is definitely an age-related increase in the risk of a number of conditions that are at least uncomfortable.

Decreased hippocampal metabolic activity in Alzheimer patients is not reflected in the immunoreactivity of cytochrome oxidase subunits.

In the present study we have compared histochemically determined cytochrome oxidase activity with the levels of immunocytochemically stained cytochrome oxidase subunits (CO II and CO IV) and ATP synthase in the human hippocampus in relation with Alzheimer's disease. Cytochrome oxidase activity was significantly reduced in all hippocampal areas of Alzheimer patients. The protein levels of subunits II and IV were not different between control subjects and Alzheimer patients.