Normal physiological functions in two animal species with highly different vitamin d status compared to that of humans / Funciones fisiológicas normales en dos especies animales con estatus de vitamina d muy diferentes del actual en seres humanos

Mole rats live in permanent darkness, in networks of underground tunnels (which extend up to 1 km in the subsoil), excavated with their incisors, in warm and semi-arid areas of South Africa. Mole rats have an unusually impoverished vitamin D3 status with undetectable and low plasma concentrations of 25- hydroxyvitamin D3 and 1α,25-dihydroxyvitamin D3, respectively. They express 25-hydroxylase in the liver and 1-hydroxylase and 24-hydroxylase in their kidneys. The presence of specific receptors (VDR) was confirmed in the intestine, kidney, Harderʼs glands and skin. In spite of their poor vitamin D3 status, the apparent fractional intestinal absorption of calcium, magnesium and phosphate was high, always greater than 90%. Oral supplementation with cholecalciferol to mole rats did not improve the efficiency of gastrointestinal absorption of these minerals. Mole ratsdo not display the typical lesion of rickets: hypertrophic and radiolucent growth cartilages. Histological studies reported normal parameters of trabecular and cortical bone quality. Marmosets (monkeys of the New World) are not hypercalcaemic, eventhough they exhibit much higher levels of 25-hydroxyvitamin D3, 1α,25-dihydroxyvitamin D3 and parathyroid hormonethan that of rhesus monkeys and humans. Fed a high vitamin D3 intake (110 IU/day/100 g of body weight), a fraction of the experimental group was found to display osteomalacic changes in their bones: distinct increases in osteoid surface, relative osteoid volume, and active osteoclastic bone resorption. These findings suggest that some marmosets appears to suffer vitamin D-dependent rickets, type II. The maximum binding capacity of the VDR or the dissociation constant of VDR1α,25(OH)2D3 complex of mole rats and New World monkeys are distinctly different of VDR isolated from human cells. Health status of those species appears to be adaptations to the mutations of their VDR. Though rare, as mutations may occur at any time in any patient, the overall message of this review to clinicians may be: recent clinical studies strongly suggests that the normality of physiological functions might be a better indicator of the health status than the serum levels of vitamin D metabolites. (AU)

Las ratas topo viven en la oscuridad permanente, en redes de túneles subterráneos excavadas con sus incisivos (que se extienden hasta 1 km en el subsuelo), en áreas cálidas y semiáridas de Sudáfrica. Las ratas topo tienen un estatus de vitamina D3 inusualmente empobrecido con concentraciones plasmáticas indetectables de 25-hidroxivitamina D3 y bajas de 1α, 25-dihidroxivitamina D3. Poseen 25-hidroxilasa en el hígado y 1-hidroxilasa y 24-hidroxilasa en sus riñones. La presencia de receptores específicos (VDR) ha sido confirmada en el intestino, el riñón, las glándulas de Harder y la piel. A pesar de su pobre estatus de vitamina D3,la absorción fraccional intestinal aparente de calcio, magnesio y fosfato fue alta, siempre superior al 90%. La suplementación oral con colecalciferol a las ratas topo no mejoró la eficacia de la absorción gastrointestinal de estos minerales. No muestran la lesión típica del raquitismo: cartílagos de crecimiento hipertróficos y radiolúcidos. Varios estudios histológicos confirman los hallazgos radiológicos y se informan parámetros normales de la calidad ósea trabecular y cortical. Los titíes (monos del Nuevo Mundo) exhiben calcemias normales con niveles más elevados de 25-hidroxivitamina D3, 1α,25-dihidroxivitamina D3 y hormona paratiroidea que los monos rhesus y los seres humanos. Un tercio de un grupo de titíes alimentados con una alta ingesta de vitamina D3 (110 I/día/100 g de peso corporal) exhibió cambios osteomalácicos en sus huesos: aumento en la superficie osteoide, volumen osteoide y activa reabsorción osteoclástica. Estos hallazgos sugieren que una fracción de la población de titíes padece raquitismo dependiente de vitamina D, tipo II. Debido a mutaciones ocurridas hace millones de años, las máximas capacidades de ligamiento del VDR o los valores de la constante de disociación del complejo VDR-1α,25(OH)2D3 de las ratas topo o monos del Nuevo Mundo son muy diferentes de los verificables en receptores aislados de células humanas actuales. El mensaje de esta revisión a los médicos clínicos podría ser: varios estudios clínicos recientes indican que la normalidad de las funciones fisiológicas de un paciente es un mejor indicador de su salud que los niveles séricos de los metabolitos de la vitamina D. (AU)

Social condition and oxytocin neuron number in the hypothalamus of naked mole-rats (Heterocephalus glaber).

The naked mole-rat is a subterranean colonial rodent. In each colony, which can grow to as many as 300 individuals, there is only one female and 1-3 males that are reproductive and socially dominant. The remaining animals are reproductively suppressed subordinates that contribute to colony survival through their cooperative behaviors. Oxytocin is a peptide hormone that has shown relatively widespread effects on prosocial behaviors in other species. We examined whether social status affects the number of oxytocin-immunoreactive neurons in the paraventricular nucleus and the supraoptic nucleus by comparing dominant breeding animals to subordinate non-breeding workers from intact colonies. We also examined these regions in subordinate animals that had been removed from their colony and paired with an opposite- or same-sex conspecific for 6 months. Stereological analyses indicated that subordinates had significantly more oxytocin neurons in the paraventricular nucleus than breeders. Animals in both opposite- and same-sex pairs showed a decreased oxytocin neuron number compared to subordinates suggesting that status differences may be due to social condition rather than the reproductive activity of the animal per se. The effects of social status appear to be region specific as no group differences were found for oxytocin neuron number in the supraoptic nucleus. Given that subordinate naked mole-rats are kept reproductively suppressed through antagonism by the queen, we speculate that status differences are due either to oxytocin's anxiolytic properties to combat the stress of this antagonism or to its ability to promote the prosocial behaviors of subordinates.

Orexinergic neuron numbers in three species of African mole rats with rhythmic and arrhythmic chronotypes.

In the present study, orexinergic cell bodies within the brains of rhythmic and arrhythmic circadian chronotypes from three species of African mole rat (Highveld mole rat-Cryptomys hottentotus pretoriae, Ansell's mole rat--Fukomys anselli and the Damaraland mole rat--Fukomys damarensis) were identified using immunohistochemistry for orexin-A. Immunopositive orexinergic (Orx+) cell bodies were stereologically assessed and absolute numbers of orexinergic cell bodies were determined for the distinct circadian chronotypes of each species of mole rat examined. The aim of the study was to investigate whether the absolute numbers of identified orexinergic neurons differs between distinct circadian chronotypes with the hypothesis of elevated hypothalamic orexinergic neurons in the arrhythmic chronotypes compared with the rhythmic chronotypes. We found statistically significant differences between the circadian chronotypes ofF. anselli, where the arrhythmic group had higher mean numbers of hypothalamic orexin neurons compared with the rhythmic group. These differences were observed when the raw data was compared and when the raw data was corrected for body mass (M(b)) and brain mass (M(br)). For the two other species investigated, no significant differences were noted between the chronotypes, although a statistically significant difference was noted between all rhythmic and arrhythmic individuals of the current study when the counts of orexin neurons were corrected for M(b)--the arrhythmic individuals had larger numbers of orexin cells.

Cortical, callosal, and thalamic connections from primary somatosensory cortex in the naked mole-rat (Heterocephalus glaber), with special emphasis on the connectivity of the incisor representation.

We investigated the distribution of cortical, callosal, and thalamic connections from the primary somatosensory area (S1) in naked mole-rats, concentrating on lower incisor and forelimb representations. A neuronal tracer (WGA-HRP) was injected into the center of each respective representation under guidance from microelectrode recordings of neuronal activity. The locations of cells and terminals were determined by aligning plots of labeled cells with flattened cortical sections reacted for cytochrome oxidase. The S1 lower incisor area was found to have locally confined intrahemispheric connections and longer connections to a small cluster of cells in the presumptive secondary somatosensory (S2) and parietal ventral (PV) incisor fields. The S1 incisor area also had sparse connections with anterior cortex, in presumptive primary motor cortex. Homotopic callosal projections were identified between the S1 lower incisor areas in each hemisphere. Thalamocortical connections related to the incisor were confined to ventromedial portions of the ventral posterior medial subnucleus (VPM) and posterior medial nucleus (Po). Injections into the S1 forelimb area revealed reciprocal intrahemispheric connections to S2 and PV, to two areas in frontal cortex, and to two areas posterior to S1 that appear homologous to posterior lateral area and posterior medial area in rats. The S1 forelimb representation also had callosal projections to the contralateral S1 limb area and to contralateral S2 and PV. Thalamic distribution of label from forelimb injections included ventral portions of the ventral posterior lateral subnucleus (VPL), dorsolateral Po, the ventral lateral nucleus, and the ventral medial nucleus and neighboring intralaminar nuclei.

Auditory activation of "visual" cortical areas in the blind mole rat (Spalax ehrenbergi).

The mole rat (Spalax ehrenbergi) is a subterranean rodent whose adaptations to its fossorial life include an extremely reduced peripheral visual system and an auditory system suited for the perception of vibratory stimuli. We have previously shown that in this blind rodent the dorsal lateral geniculate nucleus, the primary visual thalamic nucleus of sighted mammals, is activated by auditory stimuli. In this report we focus on the manifestation of this cross-modal compensation at the cortical level. Cyto- and myeloarchitectural analyses of the occipital area showed that despite the almost total blindness of the mole rat this area has retained the organization of a typical mammalian primary visual cortex. Application of the metabolic marker 2-deoxyglucose and electrophysiological recording of evoked field potentials and single-unit activity disclosed that a considerable part of this area is activated by auditory stimuli. Previous neuronal tracing studies had revealed the origin of the bulk of this auditory input to be the dorsal lateral geniculate nucleus which itself receives auditory input from the inferior colliculus.