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PubMed1990

Auditory brainstem of the ferret: early cessation of developmental sensitivity of neurons in the cochlear nucleus to removal of the cochlea.

The role of primary afferent innervation in the maintenance of neurons in the mammalian auditory system was assessed by performing unilateral removals of the cochlea in neonatal and mature ferrets of known birth dates. Removals were performed under steroid anesthesia and resulted in the complete destruction of the organ of Corti and the loss of at least 80% of type I spiral ganglion neurons. Four main age groups [postnatal days (P)5, P24, P90, and P180] were used. Additional animals received no surgery, partial removals, or complete removals at older ages. Three months after the cochlear removal the animals were reanesthetized and perfused. The brainstem and the temporal bones were wax-embedded, frontally sectioned, and Nissl-stained. Sections of the right and left cochlear nuclei were compared quantitatively. Removal of the cochlea at P5 resulted in the loss of more than 50% of large (nongranular) neurons throughout the ipsilateral cochlear nucleus. Lesions at older ages did not produce any neuron loss. The size of the remaining neurons was reduced by 10-15% in all age groups. Partial lesions at P5 produced a graded response in the cochlear nucleus that was related to the extent of the lesion. The developmental sensitive period for the effects of cochlear removal on the ferret cochlear nucleus is therefore over before the age (P28-P30) at which the animal begins to hear. The present result differs markedly from the chicken, in which the sensitive period for removal of the cochlea persists for at least 2 months after the onset of hearing.

Afferent Pathways↗
PubMed1991

A Golgi study of dendritic development in the dorsal lateral geniculate nucleus of normal ferrets.

The development of neurons in the dorsal lateral geniculate nucleus (dLGN) of pigmented ferrets was studied by using the Golgi-Hortega technique. In adult ferrets, four dLGN cell classes were defined on the basis of somatic and dendritic morphology. Classes 1 and 2 were divided into stellate and oriented subtypes. Class 1 and 4 cells are characterized by filiform appendages, class 2 cells by club-like appendages, and class 3 cells by stalked appendages. At birth, dLGN neurons have simple dendritic arbors. During the first postnatal week, dendritic length and proximal branching density increase markedly. By postnatal day 21 (P21), dendritic morphology begins to take on mature characteristics and by the time of eye opening (P30-P35), most neurons can be classified. Also by that time, dLGN cells are covered with abundant filiform appendages. Developmental changes in appendage density were quantified for class 1 stellate cells. These data reveal that appendage density reaches a peak at P56, decreases sharply until P90, and then gradually declines to mature levels by P180. Elaboration and elimination of transient appendages occurs centrifugally; at maturity appendage density remains greater distally.

Aging↗
PubMed1991

Dendritic morphology and development in the ferret lateral superior olivary nucleus.

The dendritic morphology of cells in the lateral superior olivary nucleus was studied with the Golgi method in adult and postnatal ferrets. The lateral superior olivary nucleus in the adult ferret is a convoluted structure with an M-shape in frontal sections. The major cell type appears to have disk-shaped dendritic trees. Most dendritic trees appear to be approximately orthogonal to the curved medial-lateral axis of the nucleus. Depending on their position in the limb and on the plane of section with respect to the dendritic tree, the disk-shaped cells are either bipolar or radiate in orientation. One subclass of disk-shaped cells has secondary dendritic branches that end as tufts of tendril-like processes. In a second subclass of cells, the dendrites exhibit several orders of dichotomous branching and lack obvious tufts of terminal processes. Marginal cells are observed at the border of the nucleus and have dendrites restricted to the margins of the cell plate. The bipolar orientation of disk-shaped cells orthogonal to the axis of the limbs is already apparent by the time of birth. Transient spines and other appendages are abundant on somata and dendrites during the first postnatal week. By the end of the first postnatal month only distal appendages are found. Tufts of fine tendril-like processes appear at the ends of dendrites between postnatal days 28 and 56.

Animals↗
PubMed1992

Immunohistochemical evidence for transient expression of fibronectin in the developing dorsal lateral geniculate nucleus of the ferret.

In recent years, the important role of the extracellular matrix in neural development has been increasingly recognized. In order to begin to examine what role might be played by the extracellular matrix in the developing dorsal lateral geniculate nucleus (dLGN), the present study used immunocytochemistry to assess the distribution of a recognized extracellular matrix molecule, fibronectin (FN), during postnatal development of the ferret dLGN. Prior to the segregation of cell layers, no clear pattern of FN distribution can be distinguished within the dLGN. By P16, when layers A and A1 are separated by an interlaminar space, FN is localized in that space. By P24, FN is present not only between layers A and A1, but also within layers A and A1 as bands parallel to the laminar borders. These bands appear to correspond spatially and temporally to the development of sublaminar boundaries in the ferret (Hahm and Sur, Neurosci Abstr 14:460, 1988). By the end of the first postnatal month, immunoreactivity is diminished but still present. FN is no longer present at P44 or in the adult. Adjacent sections were incubated with antiserum to glial fibrillary acid protein (GFAP). When a laminar pattern of GFAP can be distinguished, it coincides with the interlaminar distribution of FN. The findings described here are consistent with a role for FN in the development of a laminar organization in the dLGN.

Animals↗
PubMed1992

Lucifer yellow, retrograde tracers, and fractal analysis characterise adult ferret retinal ganglion cells.

The dendritic morphology of retinal ganglion cells in the ferret was studied by the intracellular injection of lucifer yellow in fixed tissue. Ganglion cells were identified by the retrograde transport of red or green fluorescent microspheres that had been injected into different target nuclei, usually the lateral geniculate nucleus or superior colliculus. This approach allows the comparison of dendritic morphologies of ganglion cells in the same retina with different central projections and also identifies cells with branching axons. The digitised images of dendritic arbors were analysed quantitatively by a variety of measures. Dendritic complexity was assessed by calculating the fractal dimension of each arbor. The ferret has distinct alpha, beta, and gamma morphological classes of cells similar to those found in the cat. The gamma cell class was morphologically diverse and could be subdivided into "sparse," "loose," and "tight" groups, reflecting increasing dendritic complexity. Whereas the beta cell projection was limited to the lateral geniculate nucleus alone, alpha and gamma cells could project to either or both nuclei. Retinal ganglion cells labelled from the pretectal nuclei formed a morphologically distinct class of retinal ganglion cells. The ipsilateral projection lacked alpha cells and the most complex, "tight" gamma cells. However, ipsilaterally projecting "loose" gamma cells overlapped alpha cells in both soma and dendritic dimensions. Different morphological classes of retinal ganglion cells hence show characteristic axon behaviour both in their decussation at the chiasm and in which targets they innervate. Fractal measures were used to contrast variation within and between these identified classes.

Animals↗
PubMed1992

Ultrastructural development of the medial superior olive (MSO) in the ferret.

When ferrets are born, four weeks before the onset of hearing, few synapses are evident in the medial superior olive (MSO). The synapses present are immature and almost exclusively found in the neuropil. The MSO somata are virtually devoid of synaptic contacts but are contacted by fine glial processes that increasingly ensheathe the somata during the first postnatal week. By P12, somatic synaptogenesis in the MSO is evident. Initially the terminals contain vesicles of irregular shape, size, and distribution. The glial lamellae appear to withdraw as the synaptic contacts form but continue to cover the asynaptic portions of the cell surface. The lamellae frequently extend from ensheathing the soma to encapsulate the immature terminals. During the next two weeks, synaptic density and terminal encapsulation proceed until the somata is surrounded by encapsulated synaptic terminals as in the adult ferret MSO. While most immature terminals contain round vesicles, during the first postnatal week some terminals with nonround vesicles can be distinguished. The first distinction between types of nonround vesicle-containing terminals, i.e., pleiomorphic and ovoid, is in the second postnatal week. This distinction becomes increasingly clear and by the end of the first postnatal month, terminal types can be reliably categorized. These observations indicate that: (1) synapses are present in the MSO neuropil one month prior to the onset of hearing, (2) the major period of synaptogenesis begins approximately two weeks prior to the onset of hearing, and (3) glial lamellae ensheathe MSO somata prior to the onset of somatic synaptogenesis, withdraw as synapses form, and subsequently re-extend to encapsulate newly formed synapses.

Animals↗
PubMed1994

Auditory brainstem of the ferret: long survival following cochlear removal progressively changes projections from the cochlear nucleus to the inferior colliculus.

Some effects on auditory brainstem connections of long (1-2.3 years) survival following unilateral cochlear removal in infant and adolescent ferrets were examined by making multiple injections of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) in either the left or the right inferior colliculus (IC). Previous studies have shown that, in normal adult ferrets, about 50 times as many cochlear nucleus (CN) neurons project to the contralateral as to the ipsilateral IC. Right cochlear removal at P25 increased, within 30 days, the number of retrogradely labeled left CN neurons projecting to the left ipsilateral IC by 17% (from n = 235 to n = 275), relative to normals. In this study, longer survival (3 months to 1 year) after right cochlear removal at P25 resulted in larger increases (38-47%; n = 100) in the number of neurons labeled in the left CN after injections of WGA-HRP in the left IC. No change occurred in the number of neurons labeled in the right CN. Taken together, the results of these experiments show that the ratio of the number of labeled neurons in the left CN to that in the right CN increases progressively with survival time out to the maximum time tested (1 year). In contrast to these results, we have previously reported that right cochlear removal at P90 did not change the number of neurons projecting from the left CN to the left IC after 90 days of survival. However, in this study, very long survival (2.3 years) following right cochlear removal at P90 resulted in an increased (51%, from n = 235 to n = 355) number of left CN neurons labeled by WGA-HRP injections into the left IC, relative to normals. The increased number of labeled neurons included neurons throughout each division of the CN and all of the principal morphological types. In a separate series of experiments involving long survival (1-2 years), right cochlear removal at P25 or P40 did not significantly change the number of neurons in either CN retrogradely labeled by injections of WGA-HRP in the right IC, or the ratio between the number of neurons labeled in each CN. Long survival following cochlear removal at P25-P90 did not result in any loss of neurons in the ipsilateral CN or in any shrinkage of CN neurons further than the 10-20% seen at a shorter survival time (90 days).(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗
PubMed1994

Expression of a keratin sulfate proteoglycan during development of the dorsal lateral geniculate nucleus in the ferret.

ABAKAN is a keratin sulfate proteoglycan that was identified in rat brain by monoclonal antibody TED15 (Geisert et al. [1992] Brain Res. 571:165-168). It blocks neuronal attachment and neurite outgrowth in culture, is associated with astrocytes, and marks the boundaries of areas in the developing rat brain (Geisert and Bidanset [1993] Dev. Brain Res., 75:163-173). In the present study TED15 was used to examine the distribution of ABAKAN during laminar development of the dorsal lateral geniculate nucleus in ferrets. This distribution was also compared with that of astrocytes as displayed with antibodies to GFAP. In the adult, TED15 and anti-glial fibrillary acidic protein (GFAP) labeling are similar. Both are fairly uniform in the nucleus although somewhat elevated near the optic tract and in the interlaminar zone between laminae A and A1. During development the pattern is quite different. At postnatal day 1 (P1), before lamination is evident, TED15 and anti-GFAP labeling are light in the nucleus. By P10, when laminae are emerging, both are elevated in the A-A1 interlaminar zone and in the C laminae. At P18, when laminae are distinct, TED15 labels the A-A1 interlaminar zone, and it marks the borders between the ON and OFF leaflets within A and A1 (Stryker and Zahs [1983] J. Neurosci. 3:1943-1951). In comparison, anti-GFAP marks the interlaminar zone but not the ON/OFF leaflets. By 6 weeks the nucleus resembles the adult nucleus. These results show that ABAKAN marks the boundaries of the major functional subdivisions of the lateral geniculate nucleus in the developing ferret and suggest that it plays a role in lamination.

Animals↗
PubMed1976

Position reversal deficit in young ferrets.

Young ferrets (6 and 10 weeks old at the start of the experiments) were compared to adult ferrets on learning (1) a Lashley III maze, (2) a left-right discrimination in T-maze with identical choice arms, and (3) a reversal of the left-right discrimination. The young were not inferior to the adults in learning either the Lashley III maze or the initial discrimination in the T-maze. However, the young were markedly (and significantly) inferior to the adults in learning to reverse.

Age Factors↗
PubMed1982

Effects of early social experience on activity and object investigation in the ferret.

Earlier experiments have shown that many of the effects of early social isolation in the rat may be due to deprivation of social play. The isolated ferret, like the isolated rat, is hyperactive; furthermore, its hyperactivity appears to be related to deprivation of social play. However, the relationship between object investigation and social rearing is more complex in the ferret than it is in the rat.

Animals↗
PubMed1987

Inhalation toxicity of ribavirin in suckling ferrets.

Ribavirin is a broad-spectrum antiviral agent useful for treatment of infants. To study the effects in developing mammalian lungs, four groups of jill ferrets and their litters were given whole body inhalation exposures for 6 h a day for 10 or 30 consecutive days to concentrations of 0 (vehicle control), 162, 355 or 620 mg/m3. The effects, including special lung observations in suckling kits, were evaluated after exposures at weaning and at puberty. First the high dose, then the mid dose jills developed lactation failure. Probably due to nutritional deficiency, approximately half of the mid dose and three quarters of the high dose kits were found dead or killed whilst moribund. There were no test compound-related deaths in the control or low dose level groups. Reductions in body weight gain were observed in both 10 and 30 day exposed kits, and high dose kits actually lost weight as exposure continued. Some recovery was apparent in survivors. Some discoloration of the liver was seen in malnourished kits at necropsy. There were no gross or histopathologic lesions in the lungs or tracheas of suckling ferrets attributable to the test material. Ribavirin exposure had no effect on the lavageable cell pool, while lung DNA to protein ratios showed a mild, reversible, proliferative response in smaller kits. There were no differences in lung function between controls and low dose kits of either group. Effects seen in the higher dose groups are due to differences in size. While there may have been a real dose-related enlargement of alveolar diameters at 40 days of age, this disappeared in males by puberty and did not seem toxicologically significant in females. The low dose, which corresponds to an exposure dose 4 to 6 times that used clinically, appeared to be a no-effect level.

Administration, Inhalation↗
PubMed1992

Jaw-muscle activity in ferrets, Mustela putorius furo.

Electromyographical (EMG) activity was recorded bilaterally from the masseter and temporalis muscles of alert ferrets (Mustela putorius furo) during mastication and crushing. Electromyographic activity was also recorded during biting while a bite-force transducer placed between the carnassial teeth registered forces ranging from 1.5 to 48.8 N. Linear regression analysis demonstrates that temporalis and masseter EMG activity are linearly related to bite force. Electromyographic activity from the balancing-side muscles is nearly equal to EMG activity of the working-side muscles during bone crushing with the carnassial teeth. It is hypothesized that a high percentage of balancing-side muscle activity in ferrets can be recruited during carnassial biting because the postglenoid process prevents ventral displacement of the working-side mandibular condyle.

Animals↗
PubMed2003

Role of calcineurin in activity-dependent pattern formation in the dorsal lateral geniculate nucleus of the ferret.

In the retinogeniculate pathway of the ferret, in addition to the separation of the inputs from the two eyes to form eye-specific layers, there is also an anatomical segregation of the terminal arbors of on-center retinal ganglion cells from the terminal arbors of off-center retinal ganglion cell axons to form on/off sublaminae. Sublamination normally occurs during postnatal weeks 3-4 and requires the activity of retinal afferents, N-methyl-D-aspartate receptors, nitric oxide synthase, and a target of nitric oxide, cyclic guanosine monophosphate. Calcineurin is a calcium/calmodulin dependent serine, threonine protein phosphatase suggested to mediate NMDA-receptor dependent synaptic plasticity in the hippocampus. We have examined whether calcineurin plays a role during on/off sublamination in the dorsal lateral geniculate nucleus (dLGN) of the ferret. Immunohistochemistry showed that calcineurin expression is transiently up-regulated in dLGN cells and neuropil during the period of on/off sublamination. A functional role for calcineurin during sublamination was investigated by blocking the enzyme locally via intracranial infusion of FK506. Treatment with FK506 during postnatal weeks 3-4 disrupted the appearance of sublaminae. These results suggest that calcineurin may play a role during this process of activity-dependent pattern formation in the visual pathway.

Afferent Pathways↗
PubMed1983

Normal and abnormal appearances of the 35-day ferret fetus studied by freehand (razor blade) sections and gross examination.

This communication reports the sectioning and subsequent examination of 1-mm freehand razor blade sections of the normal 35-day ferret fetus; pregnancy in the ferret lasts for 42 days. Skeletal and other abnormalities obtained after maternal treatment with teratogens, such as trypan blue, mustine hydrochloride, and sodium salicylate are included for comparison with the normal.

Abnormalities, Drug-Induced↗
PubMed1984

Fetal alcohol syndrome in the ferret (Mustela putorius).

Gastric intubation of 1.5 g ethanol/kg maternal body weight produced a significant teratogenic response in ferrets (Mustela putorius) treated once daily from gestational days 15 through 35. This response was evident by a rise in the frequency of fetuses with one or more malformations (21%), and by a rise in the frequency of litters with one or more malformed fetuses (50%). Palatoschisis and greater relative intermedial canthi distance observed in this study are diagnostic features of the fetal alcohol syndrome (FAS). Although mean (+/- SEM) peak blood alcohol levels of 207 +/- 9 mg/dl did not affect other reproductive parameters, high doses of alcohol (3.0 g/kg) resulted in the inability of treated females to consume adequate food or water, in the complete resorption of litters, and in significant maternal mortality (88%). Fetal deaths occurred prior to gestation day 17 in the high-dose alcohol group. Based on objective evaluation of differences among ethanol-treated, pair-fed sucrose-treated, and untreated ad libitum diet controls, the ferret would seem a valuable alternative animal species for future studies of FAS.

Animal Diseases↗
PubMed1997

Energy metabolism in normal and hypertrophied right ventricle of the ferret heart.

Using an isolated ferret heart preparation (Langendorff perfusion, perfusion pressure 90 mmHg), energy metabolism has been characterized in right and left ventricles from control and hypertrophied hearts. Hypertrophy was induced by pulmonary artery clipping for 30-45 days (right ventricle wall weight/body weight ratio increased by 70%). Myocardial contents of high energy phosphate compounds, glycogen and lactate, and the activities of some enzymes were biochemically measured in perfused hearts and also after ischemic arrest (30 min global ischemia). In hypertrophied right ventricles, PCr (-46%), Cr (-34%) levels, creatine kinase activity (-18%) were significantly decreased compared with control. ATP and Pi levels were not affected by hypertrophy. The adenylate energy charges were similar (0.85-0.86) in both types of heart. The activities of hexokinase (+26%), aldolase (+212%), pyruvate kinase (+14%) and glucose 6-phosphate dehydrogenase (+107%) were increased by hypertrophy. The LDH isozyme pattern was significantly changed such that LDH3 was decreased by 11%, and LDH4 and LDH5 were increased by a factor 1.4 and 2.9 respectively in hypertrophy. After 30 min of global ischemia, PCr level was decreased by 89 and 79% in control and hypertrophied ventricles respectively. ATP level was depressed by 41 in control and only by 21% in hypertrophied muscles. Altogether, the present data suggested that, in the adult ferret heart, the capacity for the ATP synthesis could be maintained during hypertrophy by the enhancement of the glycolytic pathway. The smaller decline of ATP after ischemia in hypertrophied tissue could be explained by a lower consumption of ATP in the hypertrophied compared to the control heart during the earliest period of ischemia.

Adenosine Triphosphate↗
PubMed1999

Effect of fenspiride, a non-steroidal antiinflammatory agent, on neurogenic mucus secretion in ferret trachea in vitro.

Neural mechanisms contribute to control of mucus secretion in the airways. Fenspiride is a non-steroidal antiinflammatory agent which has a variety of actions, including inhibition of neurogenic bronchoconstriction. The effect of fenspiride on neurally-mediated mucus secretion was investigated in vitro in electrically-stimulated ferret trachea, using(35)SO(4)as a mucus marker. Cholinergic secretory responses were isolated using adrenoceptor and tachykinin receptor antagonists. Tachykinin responses were isolated using cholinoceptor and adrenoceptor antagonists. Electrical stimulation increased cholinergic secretion by;90% and tachykininergic secretion by;40%. Fenspiride (1 microM-1 mM) tended to inhibit cholinergic secretion in a concentration-dependent manner, although only at 1 mM was inhibition (by 87%) significant. Inhibition by fenspiride of tachykininergic secretion was not concentration-dependent, and again significant inhibition (by 85%) was only at 1 mM. Inhibition was not due to loss of tissue viability, as assessed by restitution of secretory response after washout. Fenspiride also inhibited secretion induced by acetylcholine, but did not inhibit substance P-induced secretion. Histamine receptor antagonists increased basal secretion by 164%, whereas fenspiride did not affect basal secretion. We conclude that, in ferret trachea in vitro, fenspiride inhibits neurally-mediated mucus secretion, with antimuscarinic action the most plausible mechanism of action, but not necessarily the only mechanism.

Animals↗
PubMed1988

Peptidergic neurohormonal systems in the basal hypothalamus of the ferret and the mink: immunocytochemical study of variations during the annual reproductive cycle.

The hypothalamic systems secreting corticotropin-releasing hormone (CRF), somatostatin, oxytocin, vasopressin and luteinizing hormone-releasing hormone (LHRH) were characterized using immunochemistry, and variations were studied in relation to the recrudescence of testicular activity in the ferret and the mink, two species with opposite photoregulation of their annual reproductive cycles. Under the present conditions of study, the immunoreactivity of the CRF, somatostatin, and oxytocin systems showed no significant variation in either species. In contrast, in these two species, the immunoreactivity of the LHRH system varied considerably depending on the date of observation. The increase in the number and immunoreactivity of the LHRH-secreting neurons that occurred in November in the mink and in January in the ferret, is in agreement with previous results showing that the photoperiod plays an essential role in regulating the annual activity of the testis and that the photoperiodic environmental conditions required for the activation of the LHRH system differ between the species. Similarly, correlations could be found between an increase in immunoreactivity of the vasopressinergic axons projecting to the external median eminence and the recrudescence of testicular activity.

Animals↗