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Barry Robinson

Publications and source records attributed to Barry Robinson.

8 recordsLinked to original sources

Thyroidectomy alters the daily pattern of expression of the clock protein, PER2, in the oval nucleus of the bed nucleus of the stria terminalis and central nucleus of the amygdala in rats.

A role for thyroid hormones in the regulation of the rhythmic expression of circadian clock genes is suggested by the finding that surgical removal of the thyroid gland alters circadian behavioral and endocrine rhythms in rodents. Virtually nothing is known about the role of thyroid hormones in the regulation of clock genes responsible for the generation of circadian rhythmicity. To study this issue, we assessed in rats the effect of thyroidectomy/parathyrodectomy (TPX) on the expression of the clock protein, PER2, in the suprachiasmatic nucleus (SCN), the master circadian clock, and in a number of key limbic forebrain structures, the oval nucleus of the bed nucleus of the stria terminalis (BNSTov), the central nucleus of the amygdala (CEA), the basolateral amygdala (BLA) and the dentate gyrus (DG). TPX significantly altered the normal daily pattern of PER2 expression in the BNSTov and CEA, but had no effect on PER2 expression in the SCN, BLA and DG. Thus, although thyroid hormones modulate PER2 expression in the brain, the effect is tissue specific and therefore likely not to be mediated by a direct effect of the hormone on gene expression.

Amygdala↗

Pinealectomy does not affect diurnal PER2 expression in the rat limbic forebrain.

A role for the pineal hormone, melatonin, in the regulation of the rhythmic expression of circadian clock genes is suggested by the finding that surgical removal of the pineal gland abolishes the rhythm of expression of clock genes such as Per1 in several neural and endocrine tissues in rodents, including the caudate-putamen (CP) and nucleus accumbens, the hypophyseal pars tuberalis and adrenal cortex. Pinealectomy has no effect on clock gene rhythms in the suprachiasmatic nucleus (SCN), the master circadian clock, as well as in the eyes and heart, indicating that the effect of melatonin on clock gene rhythms is tissue specific. To further study the role of melatonin in the regulation of the rhythm of clock genes, we assessed in rats the effect of pinealectomy on the rhythm of expression of the clock protein, PER2, in a number of key limbic forebrain structures, the oval nucleus of the bed nucleus of the stria terminalis (BNST-OV), the central nucleus of the amygdala (CEA) and the hippocampus (HIPP). Despite previous evidence showing that these regions are sensitive to melatonin, pinealectomy had no effect on the daily rhythm of expression of PER2 within these structures, further supporting the view that the role of endogenous melatonin in the regulation of clock gene expression is tissue specific.

Animals↗

Modulation of human immunodeficiency virus infection by anticonvulsant drugs.

Patients with human immunodeficiency virus (HIV) infection often require treatment with anticonvulsants either for treatment of seizures or occasionally for pain control. In this study, the authors determined if the anticonvulsants phenytoin, carbamazepine, and valproate could modulate HIV replication. These drugs activated HIV replication in latently infected monocytic cells but not in latently infected lymphocytic cells at clinically relevant dosages. The activation in the monocytic cells was as a result of transactivation of HIV long terminal repeat (LTR) and could be seen at therapeutic dosages whereas no effect was seen on LTR activation in lymphocytic cells. When the drugs were used in conjunction with known transactivators of HIV LTR such as Tat and phorbol-12-myristate-13-acetate (PMA), no additive or synergistic effect was noted. Although the clinical relevance of these observations needs to be determined, these observations may suggest that monitoring of cerebrospinal fluid (CSF) viral load maybe needed in HIV-infected patients treated with anticonvulsants, because HIV-infected macrophages are important in mediating HIV dementia.

Anticonvulsants↗

The central and basolateral nuclei of the amygdala exhibit opposite diurnal rhythms of expression of the clock protein Period2.

There is considerable evidence that circadian rhythms in mammals can be modulated by emotional state, but how emotional state modulates specific circadian outputs is poorly understood. We analyzed the expression of the circadian clock protein Period2 (PER2) in three regions of the limbic forebrain known to play key roles in emotional regulation, the central nucleus of the amygdala (CEA), the basolateral amygdala (BLA), and the dentate gyrus (DG). We report here that cells in all three regions exhibit daily rhythms in expression of PER2 that are under the control of the master clock, the suprachiasmatic nucleus (SCN). The rhythm in the CEA and the rhythms in the BLA and DG are diametrically opposite in phase and are differentially affected by adrenalectomy. Adrenalectomy completely abolished the PER2 rhythm in the CEA but had no effect on the PER2 rhythms in the BLA and DG. We previously reported a rhythm in PER2 expression in the oval nucleus of the bed nucleus of the stria terminalis that is identical in phase and sensitivity to adrenalectomy to that found in the CEA. Together, these findings show that key structures of the limbic forebrain exhibit daily oscillations in clock gene expression that are controlled not only by input from the SCN but, importantly, by hormonal and neurochemical changes that normally accompany motivational and emotional states. Thus, cells within these areas are strategically positioned to integrate the inputs from the SCN and emotional states to modulate circadian rhythms downstream from the SCN clock.

Adrenalectomy↗

A circadian rhythm in the expression of PERIOD2 protein reveals a novel SCN-controlled oscillator in the oval nucleus of the bed nucleus of the stria terminalis.

Circadian rhythms in mammals are regulated not only globally by the master clock in the suprachiasmatic nucleus (SCN), but also locally by widely distributed populations of clock cells in the brain and periphery that control tissue-specific rhythmic outputs. Here we show that the oval nucleus of the bed nucleus of the stria terminalis (BNST-OV) exhibits a robust circadian rhythm in expression of the Period2 (PER2) clock protein. PER2 expression is rhythmic in the BNST-OV in rats housed under a light/dark cycle or in constant darkness, in blind rats, and in mice, and is in perfect synchrony with the PER2 rhythm of the SCN. Constant light or bilateral SCN lesions abolish the rhythm of PER2 in the BNST-OV. Large abrupt shifts in the light schedule transiently uncouple the BNST-OV rhythm from that of the SCN. Re-entrainment of the PER2 rhythm is faster in the SCN than in the BNST-OV, and it is faster after a delay than an advance shift. Bilateral adrenalectomy blunts the PER2 rhythm in the BNST-OV. Thus, the BNST-OV contains circadian clock cells that normally oscillate in synchrony with the SCN, but these cells appear to require both input from the SCN and circulating glucocorticoids to maintain their circadian oscillation. Taken together with what is known about the functional organization of the connections of the BNST-OV with systems of the brain involved in stress and motivational processes, these findings place BNST-OV oscillators in a position to influence specific physiological and behavioral rhythms downstream from the SCN clock.

Adrenalectomy↗

Melanopsin in the circadian timing system.

In mammals, circadian rhythms are generated by a light-entrainable oscillator located in the hypothalamic suprachiasmatic nucleus (SCN). Light signals reach the SCN via a dedicated retinal pathway, the retinohypothalamic tract (RHT). One question that continues to elude scientists is whether the circadian system has its own dedicated photoreceptor or photoreceptors. It is well established that conventional photoreceptors, rods and cones, are not required for circadian photoreception, suggesting that the inner retinal layer might contribute to circadian photoreception. Melanopsin, a novel photo pigment expressed in retinal ganglion cells (RGCs), has been proposed recently as a candidate circadian photoreceptor. Melanopsin-containing RGCs are intrinsically photosensitive, form part of the RHT, and contain neurotransmitters known to play a critical role in the circadian response to light. Furthermore, melanopsin-containing RGCs do not depend on inputs from rods and cones to transmit light signals to the SCN. However, based on a review of the available information about melanopsin and on new data from our laboratory, we propose that melanopsin, in itself, is not necessary for circadian photoreception. In fact, it appears that of the known photoreceptor systems, none, in and of itself, is necessary for circadian photoreception. Instead, it appears that within the photoreceptive systems there is some degree of redundancy, each contributing in some way to photic entrainment.

Animals↗

Evaluating the effectiveness of a dressing for use in malodorous, exuding wounds.

Malodorous, exuding wounds can cause problems for patients in terms of discomfort and social isolation. A prospective, noncomparative, multicenter study was conducted to evaluate the effectiveness of an odor-controlling dressing in the management of patients with chronic and acute exuding, malodorous wounds. Forty-six patients with various malodorous wounds (mean duration prior to study entry of 231.6 weeks) participated in the study. The majority of the patients were > 65 years of age (mean 70.7 years). Wound characteristics, odor, and dressing exudate absorption were assessed at baseline and at every dressing change (total: 348 dressing changes). Overall assessment of the dressing's ability was rated as good or excellent for odor control (91% of patients), exudate management (82%), and overall comfort (86%). Patient and nurse perception of odor were similar. While appropriate treatment to address the cause of exudate and wound odor remains a priority, the results of this study suggest that discomfort and isolation may be reduced through the use of odor-control dressings.

Aged↗