Infant Guinea Pigs Research Articles

Co-existence of myopia and amblyopia in a guinea pig model with monocular form deprivation.

BackgroundForm deprivation myopia is a type of ametropia, with identifiable causes in humans, that has been induced in many animals. The age of onset of myopia induced by monocular form deprivation coincides with the period of visual development in guinea pigs. However, visual acuity of form-deprived eyes in guinea pigs is not understood yet. In this study, we investigated whether monocular form deprivation would affect visual acuity in infant guinea pigs by evaluating the development of myopia and amblyopia after monocular form deprivation, and whether form deprivation myopia and amblyopia occurred simultaneously or successively.MethodsTwenty pigmented guinea pigs (2 weeks old) were randomly assigned to two groups: monocularly form-deprived (n=10), in which facemasks modified from latex balloons covered the right eye, and normal controls (n=10). Refraction, axial length, and visual acuity were measured at 4 intervals (after 0, 1, 4, and 8 weeks of form deprivation), using cycloplegic streak retinoscopy, A-scan ultrasonography (with an oscillation frequency of 10 MHz), and sweep visual evoked potentials (sweep VEPs), respectively. Sweep VEPs were performed with correction of the induced myopic refractive error.ResultsLonger deprivation periods resulted in significant refractive errors in form-deprived eyes compared with those in contralateral and normal control eyes; the axial lengths of form-deprived eyes increased significantly after 4 and 8 weeks of form deprivation. These results revealed that myopia was established at 4 weeks. The acuity of form-deprived eyes was unchanged compared to that at the pretreatment time point, while that of contralateral eyes and eyes in normal control guinea pigs improved; there were significant differences between the deprived eyes and the other two open eyes from 1 to 8 weeks of form deprivation, showing that amblyopia was possibly established during 1 week of form deprivation.ConclusionsThis study demonstrated the feasibility of using sweep VEPs to estimate the visual acuity of guinea pigs. Further, our results revealed that amblyopia likely occurred earlier than myopia; amblyopia and myopia coexisted after a long duration of monocular form deprivation in guinea pigs. Understanding this relationship may help provide insights into failures of treatment of amblyopia associated with myopic anisometropia.

Adult males buffer the cortisol response of young guinea pigs: Changes with age, mediation by behavior, and comparison with prefrontal activity

In the guinea pig, the presence of the mother buffers hypothalamic-pituitary-adrenal (HPA) responses of her young during exposure to a novel environment, and can do so even if she is anesthetized. In contrast, under comparable conditions other conspecifics (siblings, other adult females) are less effective or ineffective in doing so. However, we recently observed that an unfamiliar adult male reduced plasma cortisol elevations and increased Fos in the prefrontal cortex of preweaning pups exposed to a novel enclosure for 120min. Here we found adult males buffered the adrenocortical response of preweaning pups at 60 as well as 120min and of periadolescent guinea pigs if exposure was of 120min. Further, because males vigorously engaged in social interactions with the young during exposure, we examined the effect of behavior by comparing the impact of conscious and unconscious (anesthetized) adult males. When tested with a conscious but not unconscious male, pups exhibited reduced plasma cortisol elevations. Pups, particularly females, had greater Fos induction in the prefrontal cortex when with a conscious versus unconscious adult male. Overall, we found that an unfamiliar adult male can buffer the cortisol response of guinea pigs both before and after weaning, though more-prolonged exposure appears necessary in the older animals. Further, unlike buffering by the biological mother, the effect of the male is mediated by behavioral interactions. Thus, the buffering of the infant guinea pig's cortisol response by the mother and an unfamiliar adult male involve different underlying mechanisms.

Hippocampal neurogenesis regulates forgetting during adulthood and infancy.

Throughout life, new neurons are continuously added to the dentate gyrus. As this continuous addition remodels hippocampal circuits, computational models predict that neurogenesis leads to degradation or forgetting of established memories. Consistent with this, increasing neurogenesis after the formation of a memory was sufficient to induce forgetting in adult mice. By contrast, during infancy, when hippocampal neurogenesis levels are high and freshly generated memories tend to be rapidly forgotten (infantile amnesia), decreasing neurogenesis after memory formation mitigated forgetting. In precocial species, including guinea pigs and degus, most granule cells are generated prenatally. Consistent with reduced levels of postnatal hippocampal neurogenesis, infant guinea pigs and degus did not exhibit forgetting. However, increasing neurogenesis after memory formation induced infantile amnesia in these species.

Sensitization of depressive-like behavior during repeated maternal separation is associated with more-rapid increase in core body temperature and reduced plasma cortisol levels

Infant guinea pigs exhibit a 2-stage response to maternal separation: an initial active stage, characterized by vocalizing, and a second passive stage marked by depressive-like behavior (hunched posture, prolonged eye-closure, extensive piloerection) that appears to be mediated by proinflammatory activity. Recently we found that pups showed an enhanced (i.e., sensitized) depressive-like behavioral response during repeated separation. Further, core body temperature was higher during the beginning of a second separation compared to the first, suggesting a more-rapid stress-induced febrile response to separation the second day, though the possibility that temperature was already elevated prior to the second separation could not be ruled out. Therefore, the present study examined temperature prior to, and during, 2 daily separations. We also examined the temperature response to a third separation conducted 3days after the second, and assessed the effect of repeated separation on plasma cortisol levels. Core temperature did not differ just prior to the separations, but showed a more-rapid increase and then decline during both a second and third separation than during a first. Temperature responses were not associated with changes in motor activity. Depressive-like behavior was greater during the second and third separations. Pups separated a first time showed a larger plasma cortisol response at the conclusion of separation than did animals of the same age separated a third time. In all, the results indicate that the sensitization of depressive-like behavior during repeated separations over several days is accompanied by a more-rapid febrile response that may be related to a reduction of glucocorticoid suppression.

Infant guinea pig retina model of glutamate toxicity and intervention of basic fibroblast growth factor

Impaired vision with oligemic ophthalmopathy is a result of excitotoxicity caused by excitatory amino acids, resulting in pathological changes, such as loss of retinal neurons and in particular retinal ganglionic cells. The present study utilized infant guinea pigs, aged 45-50 days, to establish injury models via intraperitoneal injection of fixed sodium glutamate doses. Results from hematoxylineosin staining revealed significantly reduced retinal ganglionic cell numbers and retinal damage at 10 days after 7 consecutive days of 3 g/kg sodium glutamate treatment; these animals served as the injury model group. In addition, models of moderate injury (glutamate 3 g/kg daily, for 7 consecutive days) were intraperitoneally pretreated with basic fibroblast growth factor (800 U/kg daily). Immunohistochemistry results confirmed reduced anti-apoptotic gene bcl-2 expression in the ganglion cell layer of glutamate-injured guinea pigs. Expression of the pro-apoptotic gene caspase-3 was increased in the ganglion cell layer and inner plexiform layer. Somatostatin expression was primarily distributed in the ganglion cell layer and inner nuclear layer. Expression of the presynaptic element synaptophysin was weak. However, following basic fibroblast growth factor injection, expressions of the above-described bioactive molecules were reversed, which suggested that basic fibroblast growth factor exerted protective effects on sodium glutamate-induced retinal injury in infant guinea pigs by regulating expression of synaptophysin, somatostatin, Bcl-2, and caspase-3.

An investigation of the effects of maternal separation and novelty on central mechanisms mediating pituitary-adrenal activity in infant guinea pigs (Cavia porcellus).

In mammalian species in which the young exhibit a strong filial attachment (e.g., monkeys, guinea pigs), numerous studies have shown that even brief separation from the attachment figure potently elevates circulating concentrations of glucocorticoids and adrenocorticotropic hormone (ACTH). However, effects of separation on central regulation of this stress response are not known. Therefore, we investigated central mechanisms mediating pituitary-adrenal activation during maternal separation and novelty exposure in guinea pig (Cavia porcellus) pups. Corticotropin-releasing factor (CRF) mRNA expression in the hypothalamic paraventricular nucleus (PVN), and plasma cortisol and ACTH levels, were elevated only during separation in a novel environment. C-Fos activity was elevated in the medial amygdala (MeA) and reduced in the bed nucleus of the stria terminalis (BNST) during novelty exposure, regardless of separation. On the other hand, c-Fos activity was elevated in the PVN during separation, regardless of novelty exposure. These results demonstrate independent and combined effects of separation and novelty in regions of the guinea pig CNS that regulate pituitary-adrenal activity. Moreover, they suggest that a pathway from MeA to BNST to PVN mediates responses to novelty in the guinea pig pup, as in the adult rat, though inputs from other cell populations appear required to fully account for the HPA activity observed here.

Reduced spontaneous relaxation in immature guinea pig airway smooth muscle is associated with increased prostanoid release

Airway smooth muscle (ASM) from infant guinea pigs has less spontaneous relaxation during stimulation than ASM from adults. Inhibition of cyclooxygenase (COX), which catalyzes the production of prostanoids, increases this relaxation in infant ASM and abolishes age differences, thus suggesting that prostanoids reduce relaxation in infant ASM. In this study, we investigated whether leukotrienes are also involved in reducing spontaneous relaxation; whether the two COX isoforms, COX-1 and COX-2, differentially regulate spontaneous relaxation; and whether prostanoid release is developmentally regulated in guinea pig ASM. In different age groups, we measured relaxation during and after electrical stimulation in tracheal strips as well as prostanoid release from tracheal segments. Relaxation was studied in the absence and in the presence of a lipoxygenase inhibitor, a cysteinyl leukotriene receptor-1 antagonist, a COX-1 inhibitor, or a COX-2 inhibitor. We found that inhibition of lipoxygenase or cysteinyl leukotriene receptor-1 antagonism did not increase spontaneous relaxation at any age, thus excluding a role for leukotrienes in this phenomenon. Inhibition of COX-2, but not COX-1, promoted spontaneous relaxation. The basal release of prostanoids was more abundant in tissue from infant animals and decreased significantly with age. Thromboxane B2 was the most abundant metabolite released at all ages. Electrical stimulation and epithelium removal did not affect the age difference in prostanoid release. We conclude that increased basal prostanoid release contributes to the reduced spontaneous relaxation in immature guinea pig ASM compared with older animals. By regulating ASM relaxation, prostanoids may play a role in the airway hyperresponsiveness at a young age.

Recovery from axial myopia induced by a monocularly deprived facemask in adolescent (7-week-old) guinea pigs

Purpose Guinea pigs have been increasingly used as an animal model for experimental myopia. Infant guinea pigs are susceptible to recovery from myopia within 2 weeks of form deprivation. This study investigated whether adolescent guinea pigs are susceptible to recovery from myopia after a longer period of form deprivation. Method Twenty-two guinea pigs (age of 3 weeks) were randomly assigned to two groups: MDF (monocularly deprived facemask, n = 11) and normal control (free of form deprivation, n = 11). All animals underwent biometric measurement (refraction, corneal curvature and axial length) prior to the experiment. Animals in the MDF group wore a facemask that covered the right eye for 4 weeks. The MDF was then removed and biometric measurement was performed immediately and at 2, 6, 10 and 14 days. The same measurement was performed in the normal control group at time-points matching those of the MDF group. Results The MDF eyes were approximately 4 D more myopic with a greater increase in vitreous length by 0.12 mm compared to either the fellow or the normal control eyes after form deprivation ( p < 0.01). This relative myopia shifted rapidly towards hyperopia within 2 days after removal of the MDF, followed by a more gradual recovery. A complete recovery occurred by 6 days after removal of the MDF compared to the fellow and normal control eyes ( p > 0.05). Vitreous length in the MDF eyes slightly reduced within 2 days after removal of the MDF and then remained steady. The MDF eyes were similar to both the fellow and normal control eyes in vitreous length ( p > 0.05) 6 days after removal of the MDF. There was no significant difference between the MDF, fellow and normal control eyes in the other axial components during the form deprivation and recovery period. Conclusion Adolescent guinea pigs are susceptible to recovery from MDF-induced myopia. The refractive recovery is mainly correlated to the inhibited axial elongation of the vitreous chamber of the previously deprived eyes.

Length oscillation induces force potentiation in infant guinea pig airway smooth muscle

Deep inspiration counteracts bronchospasm in normal subjects but triggers further bronchoconstriction in hyperresponsive airways. Although the exact mechanisms for this contrary response by normal and hyperresponsive airways are unclear, it has been suggested that the phenomenon is related to changes in force-generating ability of airway smooth muscle after mechanical oscillation. It is known that healthy immature airways of both humans and animals exhibit hyperresponsiveness. We hypothesize that the profile of active force generation after mechanical oscillation changes with maturation and that this change contributes to the expression of airway hyperresponsiveness in juveniles. We examined the effect of an acute sinusoidal length oscillation on the force-generating ability of tracheal smooth muscle from 1 wk, 3 wk, and 2- to 3-mo-old guinea pigs. We found that the length oscillation produced 15-20% initial reduction in active force equally in all age groups. This was followed by a force recovery profile that displayed striking maturation-specific features. Unique to tracheal strips from 1-wk-old animals, active force potentiated beyond the maximal force generated before oscillation. We also found that actin polymerization was required in force recovery and that prostanoids contributed to the maturation-specific force potentiation in immature airway smooth muscle. Our results suggest a potentiated mechanosensitive contractile property of hyperresponsive airway smooth muscle. This can account for further bronchoconstriction triggered by deep inspiration in hyperresponsive airways.

Development of Isolation-Induced Vocal Behavior in Normal-Hearing and Deafened Guinea Pig Infants

Infants in many different animal species require auditory information from conspecifics to learn appropriate responses to important environmental and social cues. Isolation calls are emitted by infant guinea pigs in contexts of social separation from their mothers. The aim of the present study was to examine the ontogeny of the isolation calls in normal-hearing and deafened infant guinea pigs, from 2 to 40 days postpartum and to determine the role of hearing maternal vocalization in infant guinea pig vocal responses in contexts of social proximity and isolation. Female newborn pigmented guinea pigs (Cavia porcellus) were housed with their birth mother and siblings. Water and dry food were available ad libitum. One day postpartum, the cochlea of infants in the experimental group was destroyed. The control group consisted of normal-hearing female siblings. Vocalizations from infants in the experimental and control groups were recorded for 6 minutes when with the mother before isolation, 6 minutes when alone, and then 6 minutes when with the mother after reunion. Recordings were made 5 days per week from 2 to 40 days after birth. The duration of calling was calculated for each 6-minute period of recording. Results demonstrated that deaf infants vocalize more than normal-hearing infants during social isolation from their mothers. Vocal activity of isolated deaf and normal-hearing infants decreased substantially over development, almost disappearing by the end of the study period. These results indicate that maternal vocal behavior modulates the vocal responses of guinea pigs early in infant development and supports other evidence that the guinea pig offers a viable model for investigating audition in deaf and normal-hearing human infants.

Developmental patterns of aluminum and five essential mineral elements in the central nervous system of the fetal and infant guinea pig.

Al is found in the developing conceptus, but little information is available concerning its tissue distribution and its changes in concentration with age. Because Al has affinity for many of the same biological ligands as the essential mineral cations Ca, Mg, Zn, Fe, and Mn, we hypothesized that Al might show a pattern of developmental concentrations that was similar to one or more of these elements in the brain, a major target of Al toxicity. Concentrations of Al, Ca, Mg, Zn, Fe, and Mn were measured in spinal cord, brainstem, cerebellum, and forebrain of guinea pig fetuses on gestation day (GD) 30 and 45, at birth, and on postnatal day (PND) 3, 6, and 12. Dams were fed commercial guinea pig chow, which contained 47 micrograms Al/g. Tissue Al and Mn were measured with electrothermal atomic absorption spectrophotometry (ETAAS), and the other elements with inductively coupled axial plasma spectroscopy (ICAP-AES). Al concentrations in the brain regions were highest in spinal cord, brainstem, and cerebellum, and decreased during late gestation and lactation. Al did not show marked increases in regional brain concentrations during the final third of gestation as did Fe, Mg, and Zn. In contrast to Fe and Ca, Al did not accumulate in placenta. Al was the only element to show higher concentrations in spinal cord than in any other tissue at birth. In summary, the tissue distribution of Al did not follow that of essential cations as examined in this study.

Response to maternal separation in infant guinea pigs exposed to intrapartum meperidine.

We investigated whether opiate analgesics as commonly administered to women during labor would affect later response to maternal separation in infant guinea pigs. Meperidine hydrochloride (10-15 mg/kg i.m.) was administered to late-pregnant guinea pigs 5 min prior to labor induction with oxytocin. On Day 11 or 12 postnatal, pup distress vocalizations, locomotor activity, and plasma cortisol were measured under one of two conditions: alone (alone in a novel environment for 30 min) or mother (with the dam in the novel environment). Female pups exposed to intrapartum meperidine emitted fewer vocalizations than controls in the alone condition. Plasma cortisol was higher in meperidine females in the alone condition than in controls at the end of the separation period, but the difference was not significant. There was no drug effect on vocalizations or cortisol in males. Neither test condition nor drug affected activity level. The data suggest that intrapartum opiates may alter separation-induced distress in female guinea pig infants.

The Role of the Dura in Cranial Bone Regeneration in the Immature Animal

In an animal model, the effect of transferring mature pericranial tissues to immature animals with cranial bone defects was tested. Isogeneic guinea pigs of different ages were used: "infants" (3-4 weeks) and "adults" (> 18 months). Bilateral parietal cranial defects were made in infant guinea pigs and the guinea pigs were divided into three groups. In group 1 (n = 6), the infant periosteum was resected and replaced as an autograft on one side (control), and adult periosteum was transplanted as an isograft on the other (experiment). In group 2 (n = 5), dura was used as the variable. In group 3 (n = 5), combined dura and periosteum were the variables. After 8 weeks, there was complete or near complete bone regeneration in all animals in which infant dura was present. There was minimal to no bone regeneration in defects in which adult dura was present. Unlike dura, periosteum had little influence on the capacity of the bone to regenerate.

Light-dark variation and changes across the lactational period in the behaviors of undisturbed mother and infant guinea pigs (Cavia porcellus).

Lactating guinea pigs (Cavia porcellus) and their litters were observed by videophotography across the light/dark cycle at 1, 11, 21, and 31 days postpartum. The highest level of behavioral activity was seen in the dark, particularly in the hour after light offset. This circadian pattern was evident from Day 1 in mothers and from Day 11 in pups. Contact between mothers and pups was inversely related to activity, occurring more frequently during light. Maternal grooming of pups occurred on Day 1 and then declined: self-grooming by pups increased across days. Intake of solid food and water by pups occurred on Day 1 and increased thereafter. A nearly complete transition from nursing to independent ingestion was observed between 21-31 days of age. Overall, we document several ontogenetic changes in young guinea pigs and demonstrate that under laboratory conditions mother and infant guinea pigs exhibit a nocturnal activity pattern.

Light^dark variation and changes across the lactational period in the behaviors of undisturbed mother and infant guinea pigs (Cavia porcellus).

Light^dark variation and changes across the lactational period in the behaviors of undisturbed mother and infant guinea pigs (Cavia porcellus).

Factors influencing cortisol and behavioral responses to maternal separation in guinea pigs.

Infant guinea pigs recently were found to respond to brief maternal separation with an increase in plasma cortisol levels. The present experiments were conducted to further characterize this response and compare it with the cortisol separation response previously observed in primates. In Experiment 1, separation of guinea pig pups from their mothers did not elevate the plasma cortisol levels of the pups at either 30 or 180 min when they remained alone in their home cages during the separation. Experiment 2 showed that cortisol levels of pups placed alone in a novel cage were greater at 30, 90, and 180 min than were those of pups placed in the cages together with their mothers. In contrast, the separated pups vocalized more than did pups tested with their mothers during the initial 30 min only. In Experiment 3, pups raised on inanimate surrogates responded less intensely to rearing-figure separation in terms of both cortisol and vocalizations than did mother-reared controls. Taken together, these results indicate both differences (response to home cage separation) and similarities (dissociation of cortisol and vocalization responses, effect of surrogate separation) in the separation responses of guinea pig and primate infants. The guinea pig model may provide a useful adjunct to primate studies for examining particular issues concerning physiological effects of brief separation from an attachment object.

Hormonal and behavioral attachment responses in infant guinea pigs.

Infant guinea pigs, 11/12 and 18/19 days of age, exhibited high rates of vocalizing and increases in plasma concentrations of cortisol when separated from their mothers for 30 min in a novel environment (unfamiliar cage in an unfamiliar room). Levels of vocalizations and plasma cortisol were significantly reduced when the pup was exposed to the novel environment with its own conscious or anesthetized mother, but not when it was exposed with an unfamiliar anesthetized lactating female. Pups spent equivalent amounts of time in physical contact with their own conscious mother, their own anesthetized mother and an unfamiliar anesthetized lactating female. Unexpectedly, when the unfamiliar cage was placed in an environmental chamber during separation, pups showed negligible increases in vocalizations and plasma cortisol levels, even when administered footshock just prior to exposure. These findings demonstrate that guinea pig pups exhibit adrenocorticoid as well as behavioral responses to maternal separation, provide further evidence for the existence of filial attachment in this species, and document an unexpected role of the test environment in determining responses during maternal separation. The guinea pig may afford a rodent model for examining the effects of attachment-object separation on the activity of the pituitary-adrenal system.

Cortisol and behavioral responses to separation in mother and infant guinea pigs

In Experiment 1, lactating guinea pigs 3 days postpartum exhibited an elevation of plasma levels of cortisol when their litters were taken from the home cage and placed out of auditory range for 30 min. If pups were left within auditory range during the period of separation, or if the litter was disturbed but not removed, no increase in plasma cortisol levels was observed. In Experiment 2, 11/12- and 18/19-day-old guinea pig pups placed alone in a novel environment for 30 min displayed levels of plasma cortisol and vocalizations that were greater than those of pups tested in the same environment but with their mother. Pups tested with littermates but not with their mother exhibited plasma cortisol levels that were as great as those of pups tested alone. Pups tested with littermates vocalized much less than pups tested alone but more than pups tested with their mother. These results indicate that brief mother-infant separation can activate the pituitary-adrenal system in mother as well as infant guinea pigs and they provide further evidence for the existence of a reciprocal mother-infant attachment in this species.

Heart-rate responses of infant rats and guinea pigs to stimulus onset and offset: tests of the generality of a bidirectional effect

To test the generality, across modality and across species, of a bidirectional effect of photic stimulation in infant rats found in previous experiments, two experiments examined the effects on heart rate (HR) of onset and offset of auditory stimulation in rats and of photic stimulation in guinea pigs. Experiment 1 demonstrated a unidirectional, decelerative response in rats 17 and 21 days of age to the onset and offset of a 1-kHz tone, at both low (80 dB) and high (100 dB) intensity levels and at 14 days to the onset of the high-intensity tone. Experiment 2 demonstrated that infant guinea pigs, which unlike infant rats are precocial and not nocturnal, responded to the offset but not to the onset of light, and that this response was decelerative. These results indicated a lack of generality of the bidirectional HR effect, and were discussed in terms of the orienting/defensive reflex distinction.

Guinea pig herpesvirus detected as a guinea pig kidney cell culture contaminant in Mexico.

A cytopathic virus was isolated from the primary kidney cell cultures of apparently healthy guinea pigs reproduced in Mexico between 1982 and 1983. This virus produced intranuclear type A inclusion bodies in the infected cell cultures. Viral replication was inhibited by IUdR, indicating that the viral nucleic acid was DNA. The virus was sensitive to ether, chloroform and acid (pH 3.0), and passed readily through a 200 nm filter, but not through a 100 nm filter. Electron microscopy showed a spherical particle with envelope. These properties were consistent with those of Herpesviridae. In serologic survey of guinea pigs in Mexico and Japan, and of mice, hamsters, rats, rabbits, pigs, goats, horses and calves in Japan, neutralizing antibody against the isolate GPM 83-11 was detected in 4 of 46 infant guinea pigs about 3-4 weeks of age and in 9 of 30 breeding guinea pigs reproduced in Mexico, but neither in any of guinea pigs nor other animals in Japan.