The effects of viscero-somatic interactions on thalamic mast cell recruitment in cystitic rats.

Mast cells accessing the brain parenchyma through the blood-brain barrier in healthy animals are limited to pre-cortical sensory relays - the olfactory bulb and the thalamus. We have demonstrated that unilateral repetitive stimulation of the abdominal wall generates asymmetry in midline thalamic mast cell (TMC) distribution in cyclophosphamide-injected rats, consisting of contralateral side-prevalence with respect to the abdominal wall stimulation. TMC asymmetry 1) was generated in strict relation with cystitis, and was absent in disease-free and mesna-treated animals, 2) was restricted to the anterior portion of the paraventricular pars anterior and reuniens nuclei subregion, i.e., the rostralmost part of the paraventricular thalamic nucleus, the only thalamic area associated with viscero-vagal and somatic inputs, via the nucleus of the solitary tract, and via the medial contingent of the spinothalamic tract, respectively, and 3) originated from somatic tissues, i.e., the abdominal wall where bladder inflammation generates secondary somatic hyperesthesia leading to referred pain in humans. Present data suggest that TMCs may be involved in thalamic sensory processes, including some aspects of visceral pain and abnormal visceral/somatic interactions.

Increase of rat medial habenular mast cell numbers by systemic administration of cyclophosphamide.

Cyclophosphamide administration generates systemic toxicity having immune and nervous consequences. After focusing on nervous consequences by studying neuronal activity, we now consider cyclophosphamide impact on diencephalic mast cells as part of the brain immune system. Diencephalon, the ultimate sensory relay before neocortical processing, is the only brain structure containing mast cells. Single cyclophosphamide administration (100 mg/(kg 1 ml ip)) was performed in naturally behaving rats and diencephalic mast cell numbers were analyzed once all drug effects had developed (4 h postinjection). Significant increases were observed only in the medial habenular nucleus--bilaterally and especially in its caudal portion. Mast cell increase is temporally related to behavioral impairment and evoked neuronal activity in a restricted number of visceral/limbic extrathalamic structures. The medial habenular nucleus belongs to the limbic system involved in processing emotional reactions and regulation of the autonomic nervous system. Its involvement during toxic challenge is highly compatible with its presumed function in the maintenance of vital functions.

Developmental study in the circadian clock of the golden hamster: a putative role of astrocytes.

The hypothalamic suprachiasmatic nuclei (SCN) house the circadian clock in the mammalian brain. A glial fibrillary acidic protein immunoreactivity (GFAP-ir) distribution rhythm has been observed in the SCN of adult Syrian hamster. The implication of astrocytes in photic entrainment was analyzed through developmental studies of the photic pathway and of SCN astrocytes appearance. Using anterograde tracing we studied the timing of penetration of the retinohypothalamic tract (RHT) fibers into the SCN. Using c-fos induction by light we followed the maturation of RHT synapses in the SCN. When RHT terminals reach the SCN, c-fos induction can be obtained. Using GFAP immunoreactivity we demonstrated that the number of astrocytes increased in parallel with RHT development from PN5 to PN15. At PN15, a time when pups can shift from maternal to photic entrainment, RHT terminals and GFAP-ir exhibit an adult-like pattern. One demonstrated role of astrocytes is to control extracellular glutamate concentration. Glutamate is the neurotransmitter released at RHT terminals; its content fluctuates according to a circadian rhythm within the SCN. Thus the present data tend to indicate that SCN astrocytes are participating in the circadian rhythm of SCN glutamate content.

Photic induction and circadian expression of Fos-like protein. Immunohistochemical study in the retina and suprachiasmatic nuclei of hamster.

Fos-immunohistochemistry was performed in the retina and at four rostro-caudal levels of the suprachiasmatic nuclei (SCN) in hamsters. Animals were sacrificed at four circadian times (CT) relative to activity onset (CT12): CT07, 11, 14, 19 either in permanent darkness (DD) or 1 h after light stimulation. Quantification of immunoreactive nuclei showed (i) endogenous CT related changes exclusively within the rostral SCN with maximum immunoreactivity at CT07, (ii) CT related responses to light in retinal displaced amacrines, ganglion cells and caudal SCN (maximum at CT19), (iii) expression differences in four subsets of SCN cells according to CT. The rostral subset could be implicated in the endogenous clock mechanism since it exhibited a fluctuation of Fos immunoreactivity in DD and expression of Fos protein at CTs 06 and 18 when light provokes transients in the free-running period. In the caudal SCN, a ventro-laterally localized set responded to light at CTs 13 and 18, a dorsal crescent of cells responded only at CT18 and a group located laterally between these two responded at CT18. These cellular subsets may have different functions in the light-entrainment mechanism since light stimuli at CT13 induced phase-delays and, at CT18, phase-advances in the onset of the free-running locomotor activity rhythm.