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Synthesis of dehydroepiandrosterone (DHEA) by the fetal adrenal gland is important for placental oestrogen production, and may also be important for modulating the effects of glucocorticoids on the developing brain. We have preciously shown that the enzymes and accessory proteins needed for DHEA synthesis—cytochrome P450 enzyme 17α-hydroxylase/17,20 lyase (P450c17), cytochrome-b5 (Cytb5), 3β-hydroxysteroid dehydrogenase (3βHSD)—are expressed in the adrenal gland from 30 days gestation, and DHEA, cortisol and aldosterone are present in fetal plasma from this time. Explant culture of fetal adrenal tissue showed that the spiny mouse adrenal gland, can synthesize and secrete DHEA from at least 0.75 of gestation, and suggest that DHEA may have an important role(s) in placental biosynthesis of oestrogens and in modulating the actions of glucocorticoids in the developing brain in this species. Post-natally, increased immuno-expression of P450c17 and Cytb5 expression in the zona reticularis of the adrenal gland and a significant increase in the synthesis and secretion of DHEA in plasma from 8 to 20 days of age in the spiny mouse, are representative of a period of high adrenal androgen production consistent with the human phenomenon of adrenarche. The studies summarised in this review also show that DHEA is produced de novo in the developing brain of the spiny mouse. These results showed that the spiny mouse brain can indeed produce DHEA from pregnenolone in a time-dependant manner, and coupled with the identification of P450c17 and Cytb5 protein in several regions of the brain, support the idea that DHEA is an endogenous neuro-active steroid in this species. Together, the studies outlined in this review indicate that the androgen DHEA is an important hormone of adrenal and Central Nervous System (CNS) origin in the fetal and postnatal spiny mouse. Disturbance of the development of these fetal tissues, and/or of the relationship between the fetal adrenal gland and placenta during pregnancy, may have significant consequences for fetal development, placental function, and maturation of the brain. It is proposed that such disturbances of normal adrenal function could account for some of the neuropathologies that arise in juvenile and adult offspring following illness and stress experienced by the mother during pregnancy. [ABSTRACT FROM AUTHOR]

Birth asphyxia or hypoxia arises from impaired placental gas exchange during labor and remains one of the leading causes of neonatal morbidity and mortality worldwide. It is a condition that can strike in pregnancies that have been uneventful until these final moments, and leads to fundamental loss of cellular energy reserves in the newborn. The cascade of metabolic changes that occurs in the brain at birth as a result of hypoxia can lead to significant damage that evolves over several hours and days, the severity of which can be ameliorated with therapeutic cerebral hypothermia. However, this treatment is only applied to a subset of newborns that meet strict inclusion criteria and is usually administered only in facilities with a high level of medical surveillance. Hence, a number of neuropharmacological interventions have been suggested as adjunct therapies to improve the efficacy of hypothermia, which alone improves survival of the post-hypoxic infant but does not altogether prevent adverse neurological outcomes. In this review we discuss the prospect of using creatine as a dietary supplement during pregnancy and nutritional intervention that can significantly decrease the risk of brain damage in the event of severe oxygen deprivation at birth. Because brain damage can also arise secondarily to compromise of other fetal organs (e.g., heart, diaphragm, kidney), and that compromise of mitochondrial function under hypoxic conditions may be a common mechanism leading to damage of these tissues, we present data suggesting that dietary creatine supplementation during pregnancy may be an effective prophylaxis that can protect the fetus from the multi-organ consequences of severe hypoxia at birth. [ABSTRACT FROM AUTHOR]

While regeneration occurs in a number of taxonomic groups across the Metazoa, there are very few reports of regeneration in mammals, which generally respond to wounding with fibrotic scarring rather than regeneration. A recent report described skin shedding, skin regeneration and extensive ear punch closure in two rodent species, Acomys kempi and Acomys percivali. We examined these striking results by testing the capacity for regeneration of a third species, Acomys cahirinus, and found a remarkable capacity to repair full thickness circular punches in the ear pinna. Four-millimeter-diameter wounds closed completely in 2 months in 100% of ear punches tested. Histology showed extensive formation of elastic cartilage, adipose tissue, dermis, epidermis and abundant hair follicles in the repaired region. Furthermore, we demonstrated abundant angiogenesis and unequivocal presence of both muscle and nerve fibers in the reconstituted region; in contrast, similar wounds in C57BL/6 mice simply healed the borders of the cut by fibrotic scarring. Our results confirm the regenerative capabilities of Acomys, and suggest this model merits further attention. [ABSTRACT FROM AUTHOR]

Neacomys (Sigmodontinae) comprises 8 species mainly found in the Amazonian region. We describe 5 new karyotypes from Brazilian Amazonia: 2 cytotypes for N. paracou (2n = 56/FNa = 62-66), 1 for N. dubosti (2n = 64/FNa = 68), and 2 for Neacomys sp. (2n = 58/FNa = 64-70), with differences in the 18S rDNA. Telomeric probes did not show ITS. We provide a phylogeny using Cytb, and the analysis suggests that 2n = 56 with a high FNa is ancestral for the genus, as found in N. paracou, being retained by the ancestral forms of the other species, with an increase in 2n occurring independently in N. spinosus and N. dubosti. Alternatively, an increase in 2n may have occurred in the ancestral taxon of the other species, followed by independent 2n-reduction events in Neacomys sp. and in the ancestral species of N. tenuipes, N. guianae, N. musseri, and N. minutus. Finally, a drastic reduction event in the diploid number occurred in the ancestral species of N. musseri and N. minutus which exhibit the lowest 2n of the genus. The karyotypic variations found in both intra- and interspecific samples, associated with the molecular phylogeny, suggest a chromosomal evolution with amplification/deletion of constitutive heterochromatin and rearrangements including fusions, fissions, and pericentric inversions. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Pregnancy induces adaptations in maternal metabolism to meet the increased need for nutrients by the placenta and fetus. Creatine is an important intracellular metabolite obtained from the diet and also synthesised endogenously. Experimental evidence suggests that the fetus relies on a maternal supply of creatine for much of gestation. However, the impact of pregnancy on maternal creatine homeostasis is unclear. We hypothesise that alteration of maternal creatine homeostasis occurs during pregnancy to ensure adequate levels of this essential substrate are available for maternal tissues, the placenta and fetus. This study aimed to describe maternal creatine homeostasis from mid to late gestation in the precocial spiny mouse. Methods: Plasma creatine concentration and urinary excretion were measured from mid to late gestation in pregnant (n = 8) and age-matched virgin female spiny mice (n = 6). At term, body composition and organ weights were assessed and tissue total creatine content determined. mRNA expression of the creatine synthesising enzymes arginine:glycine amidinotransferase (AGAT) and guanidinoacetate methyltransferase (GAMT), and the creatine transporter (CrT1) were assessed by RT-qPCR. Protein expression of AGAT and GAMT was also assessed by western blot analysis. Results: Plasma creatine and renal creatine excretion decreased significantly from mid to late gestation (P < 0.001, P < 0.05, respectively). Pregnancy resulted in increased lean tissue (P < 0.01), kidney (P < 0.01), liver (P < 0.01) and heart (P < 0.05) mass at term. CrT1 expression was increased in the heart (P < 0.05) and skeletal muscle (P < 0.05) at term compared to non-pregnant tissues, and creatine content of the heart (P < 0.05) and kidney (P < 0.001) were also increased at this time. CrT1 mRNA expression was down-regulated in the liver (<0.01) and brain (<0.01) of pregnant spiny mice at term. Renal AGAT mRNA (P < 0.01) and protein (P < 0.05) expression were both significantly up-regulated at term, with decreased expression of AGAT mRNA (<0.01) and GAMT protein (<0.05) observed in the term pregnant heart. Brain AGAT (<0.01) and GAMT (<0.001) mRNA expression were also decreased at term. Conclusion: Change of maternal creatine status (increased creatine synthesis and reduced creatine excretion) may be a necessary adjustment of maternal physiology to pregnancy to meet the metabolic demands of maternal tissues, the placenta and developing fetus. [ABSTRACT FROM AUTHOR]

Stable isotope analysis is frequently applied as a tool to examine dietary patterns in animals. However, some of the underlying assumptions associated with using this approach are increasingly being questioned. We carried out a controlled diet experiment on the southern African spiny mouse ( Acomys spinosissimus Peters, 1852) to test a number of aspects relating to these assumptions and also examine the hypothesis that stable isotopes, especially δ15N, can be used to provide evidence of nutritional stress. We compared the δ13C and δ15N values of livers and blood from animals that were fed ad libitum with animals undergoing a 10% reduction in food supply. Food-restricted animals showed no significant difference in δ15N; however, δ13C values of both liver and blood were depleted. Restricted animals also had a significantly lower C:N ratio. We examined the role of lipids and found following lipid extraction that both livers and lipids still showed the same separation in carbon values. Tissue-diet discrimination values were also calculated and found to be higher for both Δ13C and Δ15N compared with other mice species. Empirical values for discrimination rates were then compared with values calculated using an alternative method based on employing generic values and were found to be dissimilar, suggesting the use of generic values are not always appropriate. Our results highlight the need for greater understanding of the assumptions associated with using stable isotope analysis to examine diet and we suggest that studying a single species under captive conditions presents an ideal method to begin to test these hypotheses. [ABSTRACT FROM AUTHOR]

We studied the effects of early weaning on immunocompetence and parasite resistance in a precocial rodent Acomys cahirinus. We hypothesized that if parasite resistance is energetically expensive and nutritional and immunological support from mothers are necessary for the long-term health of offspring, then early weaned animals would be immunologically weaker and less able to defend themselves against parasites than later weaned animals. We weaned pups at 14, 21 or 28 days after birth and assessed their immunocompetence and resistance against fleas Parapulex chephrenis when they attained adulthood. Immunocompetence was assessed using leukocyte concentration (LC) and a phytohaemagglutinin injection assay (PHA test). To estimate resistance against fleas, we measured performance of fleas via the number of produced eggs and duration of development and resistance to starvation of the flea offspring. We found a significant positive effect of weaning age on the PHA response but not on LC. The effect of age at weaning on flea egg production was manifested in male but not female hosts, with egg production being higher if a host was weaned at 14 than at 28 days. Weaning age of the host did not affect either duration of development or resistance to starvation of fleas produced by mothers fed on these hosts. We conclude that even in relatively precocial mammals, weaning age is an important indicator of future immunological responses and the ability of an animal to resist parasite infestations. Hosts weaned at an earlier age make easier, less-resistant targets for parasite infestations than hosts weaned later in life. [ABSTRACT FROM AUTHOR]

An increased incidence of mental illness disorders is found in children and adolescents born to mothers who experienced an infection-based illness during pregnancy. Animal models to study the prenatal origin of such outcomes of pregnancy have largely used conventional rodents, which are immature (altricial) at birth compared with the human neonate. In this study, we used the precocial spiny mouse (Acomys cahirinus), whose offspring have completed organogenesis at birth, and administered a single subcutaneous injection of a 5 mg/kg dose of the viral mimetic poly I:C (polyriboinosinic-polyribocytidylic acid) at mid gestation (20 days; term is 39 days). Prenatal exposure to poly I:C caused a transient weight loss in the pregnant dam, produced a downregulation of the proinflammatory cytokine tumour necrosis factor-α in the fetal brain, and resulted in abnormalities in sensorimotor gating and reduced social interaction, memory and learning in juvenile offspring. No changes in exploratory activity or anxiety and fear behaviours were found between the treatment groups. This study provides evidence that, in a rodent model that more closely resembles human brain development, prenatal infection can lead to behavioural abnormalities in postnatal life. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The circadian rhythm of locomotory activity in the Arabian spiny mouse, a desert living species, was investigated under controlled laboratory conditions. Ten individuals were subjected to successive light cycles. When subjected to a 12L:12D light cycle, locomotor activity was confined mainly to the dark phase (mean 94.2% ± 1.6%). During a period of constant darkness (DD), all animals expressed free running rhythms of locomotor activity (mean 23h49 ± 0h04). Following a second LD cycle, the light and dark phases were inversed (12D:12L). Activity shifted with the lights and was masked during the light phase, re-entrainment was rather slow (up to 10 days). The effect of varying ambient temperature (20–35 °C) on the locomotor activity under a 12L:12D cycle revealed that temperature had no distinct effect on the level of locomotor activity. When the dark component of the day was lengthened to 8L:16D, the mean percentage of activity during the dark increased to 96.0 ± 0.8%, while a significant decrease in night time activity was observed when the dark phase length was decreased to 16L:8D (78.29 ± 2.52%). The Arabian spiny mouse therefore behaves as other desert dwelling rodents and can be described as truly nocturnal. [ABSTRACT FROM AUTHOR]

Regeneration of adult mammalian central nervous system (CNS) axons is abortive, resulting in inability to recover function after CNS lesion, including spinal cord injury (SCI). Here, we show that the spiny mouse (Acomys) is an exception to other mammals, being capable of spontaneous and fast restoration of function after severe SCI, re-establishing hind limb coordination. Remarkably, Acomys assembles a scarless pro-regenerative tissue at the injury site, providing a unique structural continuity of the initial spinal cord geometry. The Acomys SCI site shows robust axon regeneration of multiple tracts, synapse formation, and electrophysiological signal propagation. Transcriptomic analysis of the spinal cord following transcriptome reconstruction revealed that Acomys rewires glycosylation biosynthetic pathways, culminating in a specific pro-regenerative proteoglycan signature at SCI site. Our work uncovers that a glycosylation switch is critical for axon regeneration after SCI and identifies β3gnt7 , a crucial enzyme of keratan sulfate biosynthesis, as an enhancer of axon growth. [Display omitted] • Acomys spontaneously regains motor and urinary functions following complete SCI • The Acomys SCI site shows abundant axon regeneration and nerve conduction • Acomys assembles a pro-regenerative environment with rewired ECM glycosylation • β3gnt7 is a novel axon regeneration enhancer Nogueira-Rodrigues et al. report that Acomys can recover function after complete spinal cord injury (SCI), assembling a scarless tissue at the injury site, unlike other adult mammals. Transcriptomic analysis of the SCI site shows that injured Acomys builds a specific pro-regenerative proteoglycan signature with a unique glycosylation network. [ABSTRACT FROM AUTHOR]

Animals show daily rhythms in most bodily functions, resulting from the integration of information from an endogenous circadian clock and external stimuli. These rhythms are adaptive and are expected to be related to activity patterns, i.e., to be opposite in diurnal and nocturnal species. Melatonin is secreted during the night in all mammalian species, regardless of their activity patterns. Consequently, in diurnal species the nocturnal secretion of melatonin is concurrent with the resting phase, whereas in nocturnal species it is related to an increase in activity. In this research, we examined in three diurnal and three nocturnal rodent species whether a daily rhythm in anxiety-like behavior exists; whether it differs between nocturnal and diurnal species; and how melatonin affects anxiety-like behavior in species with different activity patterns. Anxiety-like behavior levels were analyzed using the elevated plus-maze. We found a daily rhythm in anxiety-like behavior and a significant response to daytime melatonin administration in all three nocturnal species, which showed significantly lower levels of anxiety during the dark phase, and after melatonin administration. The diurnal species showed either an inverse pattern to that of the nocturnal species in anxiety-like behavior rhythm and in response to daytime melatonin injection, or no rhythm and, accordingly, no response to melatonin. [ABSTRACT FROM AUTHOR]

The genus Acomys is represented by 19 species in a vast area in the African and eastern Mediterranean regions. Acomys cilicicus, belonging to the genus Acomys, is an endemic species in Turkey. In this study, by evaluating the reproductive data in laboratory conditions and the natural habitat of A. cilicicus, the reproductive biology of the species was researched in detail for the first time. The data concerning the reproduction of 1404 samples, reproduced from 1 male and 2 females in the laboratory and 34 samples obtained from 6 localities near Silifke, were recorded. For A. cilicicus, it was determined that the pregnancy period was 38-40 days, litter size was 1-3 (n = 321, mean = 2.05), and time to maturity was 2-4 months. The newborns' eyes were closed, their auricles were bonded to the head, they had short hair, their abdomens were hairless, and their backs were dark gray. Dentition was completed within 9-10 days and therefore the newborn could easily take food. Suckling was under control of the mother and carried on for approximately 2-3 months. Furthermore, the reproductive, infanticidal, and cannibalistic behaviors of this species were monitored periodically. These data were compared with A. cahirinus, russatus, nesiotes, minous, and dimidiatus, whose reproductive biologies are known and who are close to A. cilicicus geographically. Finally, it was determined that some reproductive findings of A. cilicicus were compatible with the findings of other species, and some findings were different from those of the species above. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: It has been hypothesized that male fetuses down regulate placental growth during periods of accelerated fetal growth. We aimed to investigate this, and determine whether sexual dimorphism was apparent in the spiny mouse placenta. We hypothesized that expression of fetal growth promoters would be higher in placentas of males, whereas genes involved in placental structural development would be more highly expressed in placentas of females. Methods: Spiny mouse dams, a precocial rodent with an in utero endocrine milieu dissimilar from other rodents, but akin to humans, were sacrificed at gestational ages 15–37 (term = 39 days). Placentas were collected and processed for histology or qPCR analysis of selected genes (GCM1, MAP2K1, SLC2A1, NR3C1, IGF1, IGF1R). Results: Fetal and placental weights were similar for both sexes. Placentas of female fetuses had less spongy zone (P SEX < 0.0001), and more labyrinth (P SEX < 0.0001) than males. Early placenta and labyrinth expression of SLC2A1 was higher in males than females (P SEX < 0.05). Labyrinthine IGF1R remained constant until term in the female, compared with male where expression increased until term. Peak MAP2K1 expression occurred earlier in the male placenta than the female. Spongy zone SLC2A1 remained constant until term in the female, compared with male where expression increased until term. Conclusions: The spiny mouse is a species that exhibits sexually dimorphic placental development. We suggest that these sex differences in placental gene expression and structure may underlie or compound the male vulnerability to a sub-optimal in utero environment. [Copyright &y& Elsevier]

Abstract: Epidemiological studies have suggested a link between prenatal exposure to bacterial or viral infections and subsequent development of mental disorders such as schizophrenia and autism. Animal models to study the prenatal origin of such outcomes of pregnancy have largely used conventional rodents which are immature at birth compared to the human neonate, and doses of the infective agent (i.e., lipopolysaccharide, Poly I:C) have been large enough to cause sickness behaviour in the mother. In this study we have used the spiny mouse (Acomys cahirinus) whose offspring have completed organogenesis at birth, and a single subcutaneous injection of a low (0.5mg/kg) dose of polyriboinosinic–polyribocytidilic acid (Poly I:C) at mid gestation (20days, term is 39days). The treatment had no effect on maternal, fetal or neonatal survival, or postnatal growth of the offspring. However, offspring showed significant impairments in non-spatial memory and learning tasks, and motor activity. Brain histology examined at 1 and 100days of age revealed significant decreases in reelin, increased GFAP expression, and increased numbers of activated microglia, specifically in the hippocampus. This study provides evidence that a prenatal subclinical infection can have profound effects on brain development that are long-lasting. [Copyright &y& Elsevier]

Abstract: Studies of human neonates, and in animal experiments, suggest that birth asphyxia results in functional compromise of the hippocampus, even when structural damage is not observable or resolves in early postnatal life. The aim of this study was to determine if changes in hippocampal function occur in a model of birth asphyxia in the precocial spiny mouse where it is reported there is no major lesion or infarct. Further, to assess if, as in human infants, this functional deficit has a sex-dependent component. At 37 days gestation (term=39 days) spiny mice fetuses were either delivered immediately by caesarean section (control group) or exposed to 7.5min of in utero asphyxia causing systemic acidosis and hypoxia. At 5 days of age hippocampal function was assessed ex vivo in brain slices, or brains were collected for examination of structure or protein expression. This model of birth asphyxia did not cause infarct or cystic lesion in the postnatal day 5 (P5) hippocampus, and the number of proliferating or pyknotic cells in the hippocampus was unchanged, although neuronal density in the CA1 and CA3 was increased. Protein expression of synaptophysin, brain-derived neurotrophic factor (BDNF), and the inositol trisphosphate receptor 1 (IP3R1) were all significantly increased after birth asphyxia, while long-term potentiation (LTP), paired pulse facilitation (PPF), and post-tetanic potentiation (PTP) were all reduced at P5 by birth asphyxia. In control P5 pups, PPF and synaptic fatigue were greater in female compared to male pups, and after birth asphyxia PPF and synaptic fatigue were reduced to a greater extent in female vs. male pups. In contrast, the asphyxia-induced increase in synaptophysin expression and neuronal density were greater in male pups. Thus, birth asphyxia in this precocial species causes functional deficits without major structural damage, and there is a sex-dependent effect on the hippocampus. This may be a clinically relevant model for assessing treatments delivered either before or after birth to protect this vulnerable region of the developing brain. [Copyright &y& Elsevier]

This study was designed to determine follicular atresia in the newborn and the prepubertal spiny mouse. We analyzed the processes of follicle loss using classical markers of apoptosis (TUNEL reaction, active caspase-3) and autophagy (Lamp1). Numerous small clear vacuoles and autophagosomes as well as strong Lamp1 staining were observed in dying oocytes of all follicle types, especially of the primordial and primary ones. Active caspase 3 and the TUNEL reaction were detected only in the granulosa cells of large secondary and antral follicles. The expression of apoptosis and autophagy markers was also changing during the prepubertal period. Western blot analysis indicated that at the moment of birth, females undergo an increased rate of follicular atresia mediated by autophagy, while apoptosis is the dominant form of ovarian atresia in consecutive postnatal days. On the basis of these observations, we concluded that apoptosis and autophagy are involved in follicular atresia and these processes are cell and developmental stage-specific. [ABSTRACT FROM AUTHOR]

Abstract: The possible role of increased dietary salinity as a proximate regulator of reproduction in xeric population of golden spiny mice (Acomys russatus) and mesic population of common spiny mice (A. cahirinus) was tested. In the wild, as the dry season progresses, evaporative water loss in the vegetation increases. This leads to increase in particle concentration of plant tissues. Thus, species consuming a plant diet are exposed to increased dietary salinity. Both male and female individuals of A. russatus were subjected to gradually increasing dietary salinity (0.9%, 2.5%, 3.5%, and 5%) while those of A. cahirinus only up to 3.5% for a total period of 8 and 6 weeks, respectively. Urine osmolarity showed a significant increase under 3.5% and 5% salinity in A. russatus and 2.5% and 3.5% in A. cahirinus. Testis mass and spermatogenesis were significantly reduced while uterine mass and vaginal estrus cycles were not affected in A. russatus. None of the parameters was significantly affected in A. cahirinus. Increase in salinity also significantly reduced body mass in A. russatus but not in A. cahirinus. Mass-specific daily digestible energy intake was not significantly affected by increased salinity in both species. Recovery individuals regained body mass quickly and surpassed initial values after four weeks. However, testis mass and spermatogenesis did not show recovery. The results suggest that increase in dietary salinity could be used as a proximate signal to regulate reproduction in A. russatus by halting it in males, as the dry season progresses while such role in the mesic population of A. cahirinus is unlikely. [Copyright &y& Elsevier]

Abstract: Circadian locomotor rhythms were examined in adult common spiny mice, Acomys cahirinus. Spiny mice demonstrated nocturnal activity, with onset of activity coinciding promptly with onset of darkness. Re-entrainment to 6-h delays of the light–dark cycle was accomplished faster than to 6-h advances. Access to running wheels yielded significant changes in period and duration of daily activity. Novelty-induced wheel running had no effect on phase of activity rhythms. Circadian responses to light at various times of the circadian cycle were temporally similar to those observed in other nocturnal rodent species. No gender differences were observed in any of the parameters measured. [Copyright &y& Elsevier]

The common spiny mice Acomys dimidiatus and golden spiny mice Acomys russatus coexist in the extreme warm and dry parts of the Rift Valley in Israel. However, they are temporally segregated in that the former is nocturnal, whereas the latter is diurnal. Daily rhythms of physiological and behavioral variables in A. russatus responded to semiochemical signals released by A. dimidiatus (in the urine and feces). Both species feed upon the same food items but at different times of the 24-hr cycle. The main aim of the present study was to test under field conditions the foraging response of A. russatus to odors of different ages released by A. dimidiatus. Various feeding and behavioral variables were compared in three groups of A. russatus. The results show that fresh semiochemical signals released by A. dimidiatus decrease the feeding efficiency and increase the rate of smelling from a distance in A. russatus. These results support the idea that temporal segregation between the two coexisting species is at least partly through semiochemicals present in the urine and feces. [ABSTRACT FROM AUTHOR]