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Biomedical subjects

F Haun

Publications and source records attributed to F Haun.

At least 19 recordsLinked to original sources
PubMed1996

Lesion of the habenular efferent pathway produces anxiety and locomotor hyperactivity in rats: a comparison of the effects of neonatal and adult lesions.

Recent studies have implicated the habenula in modulating states of arousal and chronic responses to stress. We examined whether lesion of the habenula efferent pathway, the fasciculus retroflexus (FR), at either 3 (P3) or 70 (P70) days of age affects stress-related anxiety (elevated plus-maze test) and activity levels (open-field test) in rats tested as adults. Both P3- and P70-lesioned rats showed chronically elevated plasma levels of corticosterone. Rats receiving FR lesions as neonates (P3) exhibited greater open arm avoidance on the elevated plus-maze than controls 2 months postoperatively, suggesting a heightened state of anxiety. In contrast, P70-lesioned rats behaved similarly to controls on the plus-maze, but showed increased locomotion and increased grooming in the open field, effects not observed in P3-lesioned rats. When an additional stressful condition was imposed (5 days of social isolation plus 24 h food deprivation) before testing, both FR-lesion groups showed an attenuation of the normal behavioral responses (decreased open-arm entries/time in open arms, increased freezing). The effects of FR lesions on activity and behavioral indices of anxiety may be due to disruption of lateral habenular projections to dopaminergic neurons in the ventral tegmentum and/or projections to regions containing high concentrations of benzodiazepine receptors, the median and dorsal raphe and dorsal periaqueductal gray. Behavioral differences observed as a function of lesion age suggest differential capabilities of P3- and P70-lesioned rats to utilize compensatory mechanisms to correct FR lesion-induced deficits.

Aging↗
PubMed1995

A role for Grb2 in apoptosis?

Src homology type 2 (SH2) and type 3 (SH3) domains appear to have an important role in signal transduction pathways initiated by tyrosine kinases. SH2 domains allow proteins with signalling functions to interact with tyrosine kinases and tyrosine-phosphorylated proteins at the plasma membrane, whereas SH3 domains allow a distinct type of interaction through binding to proline-rich sequences. The adaptor protein Grb2 consists of one SH2 domain and two SH3 domains and connects tyrosine kinase receptors to activation of the Ras pathway. Its closely related counterpart, Grb3-3, thought to arise by alternative splicing of Grb2 transcripts, lacks a functional SH2 domain but retains functional SH3 domains. We recently presented evidence that Grb3-3 might deliver specific signals causing cells to undergo apoptosis. This review will document the mechanism of Grb3-3 function and discuss its putative involvement in several pathologies. It also further strengthens the notion that cells may use alternative splicing as a means to drive either a proliferative or a suicidal program.

Journal Article↗
PubMed1994

Transient and permanent patterns of expression of the low-affinity neurotrophin receptor in the interpeduncular nucleus of the rat.

There is a prominent cholinergic projection from the medial habenular to the interpeduncular nucleus (IPN) which develops postnatally. In this study we examined the developmental course of expression of the low-affinity neurotrophin receptor (LANR), a receptor that binds to all members of the neurotrophin family, in the IPN. Three systems express LANR in the IPN. The cholinergic habenular axons that project to the intermediate and central subnuclei of the IPN are immunoreactive only during the time that the axons are growing and forming characteristic crest synapses in the intermediate subnuclei. The dorsomedial (DM) subnuclei, which are neither cholinergic targets nor contain cholinergic neurons, develop LANR immunoreactivity postnatally and the expression remains high in the adult. The walls of the prominent system of arterioles and venules that penetrate the IPN and ascend through the intermediate subnuclei are strongly immunoreactivity during the time of active angiogenesis and retain detectable but diminished levels of immunoreactivity in the adult. The LANR immunoreactivity seen in the vessels is likely to be associated with the peripheral sympathetic axons that innervate the smooth muscle in the vessels. These three systems within the same nucleus, which differ in phenotype, develop neurotrophin receptor immunoreactivity contemporaneously but their levels of expression differ in the adult, suggesting that they are regulated in different ways, possibly by different members of the neurotrophin family.

Animals↗
PubMed1994

Dissociation of behavioral changes in rats resulting from lesions of the habenula versus fasciculus retroflexus and their possible anatomical substrates.

Lesions in either the habenula or its primary efferent pathway, the fasciculus retroflexus (FR), impaired avoidance responding. However, lesions of only the FR provided a persistent elevation of locomotor activity. Immunocytochemical study of the interpeduncular nucleus (IPN) through injection of retrograde tracers into the IPN and the overlying ventral tegmental area indicated that habenular lesions spared both rostral habenula and forebrain projections to the caudal midbrain, but these projections were axotomized by FR lesions. Rostral sparing of the habenula resulted in normal peptidergic staining in the IPN, and normal cholinergic innervation was absent. Performance of individual rats in behavioral tests was consistent with variations in anatomical sparing. Such considerations may account for previous discrepancies in functional effects of habenular lesions.

Animals↗
PubMed1993

Recovery of frontal cortex-mediated visual behaviors following neurotrophic rescue of axotomized neurons in medial frontal cortex.

Unilateral lesions extending across the boundary region of visual and parietal cortex in adult rats result in the death of 20-35% of neurons in layers II-III of the caudal third of medial frontal cortex ipsilaterally, a neuron population labeled with 3H-thymidine on the 19th day of gestation (E19). Additionally, there is a consistent 15% loss of these labeled neurons in an area between 50% and 60% of the distance along the caudal-rostral extent of medial frontal cortex, an area that may function analogously to the frontal eye field of primates. All of these neurons are rescued from axotomy-induced death by delivering into the posterior cortex lesion cavity for 2 weeks a macromolecular fraction of culture medium conditioned by embryonic primordia of the frontal-occipital pathway (CM). Moreover, the rescue is apparently permanent, with normal numbers of these neurons present in CM animals 6-7 weeks after the neurotrophic factor is no longer being supplied exogenously. Behaviorally, control operates receiving a similarly prepared fraction of unconditioned medium are significantly impaired in the number of trials needed to learn two visual discrimination tasks. This deficit is attributable in part to a bias in erroneous responses to the side contralateral to the lesion. The error bias reflects a failure to inhibit repeated incorrect responding contralaterally. In contrast, the CM animals learn both visual tasks in a normal number of trials and have no contralateral error bias. Rather, all CM animals have an contralateral error bias. Rather, all CM animals have an ipsilateral error bias (interpreted as an unmasking of the contralateral neglect expected after a parietal cortex lesion).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Rescue of both rapidly and slowly degenerating neurons in the dorsal lateral geniculate nucleus of adult rats by a cortically derived neuron survival factor.

We investigated the death of dorsal lateral geniculate nucleus (dLGN) neurons after lesions to the visual cortex of adult rats and the effects of supplying target-derived neurotrophic molecules to the lesion cavity. The neurotrophic factor is retrieved from cocultures of the embryonic primordia of the geniculocortical pathway and its survival promoting properties for different populations of dLGN neurons (based on their time of origin) have been documented in previous studies of neonatal rats with occipital cortex lesions. In the present study, rats were exposed to [3H]thymidine on E14 or E15/16 to label either earlier or later generated dLGN neurons. When animals were at least 45 days old we made discrete lesions to the principal projection zones in area 17 of these two dLGN populations. Counts of surviving labeled cells show a relatively rapid death of E15/16 dLGN neurons in control animals, with a maximal loss by 2 weeks postlesion. The death of E14 dLGN neurons is more protracted, with a maximal loss by 2 months postlesion. A 2-week infusion of the CM fraction rescues the majority of the neurons that would otherwise die in both populations compared to the controls which receive a similarly prepared fraction of unconditioned medium. Moreover, this CM fraction can sustain E14-generated dLGN neurons up to 6 weeks after the neurotrophic factor(s) is no longer being supplied exogenously. Thus the rescue of axotomized adult dLGN neurons appears to be permanent, at least for the early generated population. These findings are consistent with the idea that target-derived molecules have a role in the survival of mature neurons, as they are known to have for developing neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Habenula and thalamus cell transplants mediate different specific patterns of innervation in the interpeduncular nucleus.

Innervation of specific peptidergic and cholinergic compartments of the interpeduncular nucleus (IPN) was investigated using embryonic cell suspension transplants immunoreactive for substance P (SP) and ChAT. In both neonatal and adult host rats, the IPN was first denervated of its normal SP and cholinergic input from the medial habenula by bilateral lesions of the fasciculi retroflexi (FR). In adult hosts, transplants of embryonic habenular cells placed near the denervated IPN mediated a return of the normal pattern of SP staining restricted to habenula-target subnuclei, plus an increase in staining intensity of SP cells intrinsic to the IPN. There was no recovery of ChAT staining. A similar pattern of SP staining resulted following habenular transplants into neonatal hosts, but in addition there was a partial recovery of normal ChAT staining in cholinergic subnuclei and anomalous ChAT staining in normally peptidergic subnuclei. Control transplants of embryonic thalamus cells placed into adult hosts produced a surprising pattern of ChAT staining in the IPN identical to that seen with habenula transplants placed into neonatal hosts; the adult IPN was thus able to support reinnervation mediated by an aberrant cholinergic source while being refractory to its normal habenular cholinergic afferents. This pattern of results implies regulation by the IPN of habenular SP and cholinergic innervation, and some interaction between the maturing normal cholinergic afferents and their targets that is missing when these afferent sources are abnormal.

Animals↗
PubMed1992

Habenula and thalamus cell transplants restore normal sleep behaviors disrupted by denervation of the interpeduncular nucleus.

The preceding companion study (Eckenrode et al., 1992) showed that cell suspension transplants of fetal habenula cells placed near the interpeduncular nucleus (IPN) following lesions of the fasciculus retroflexus (FR) restore the normal pattern of substance P (SP) staining in habenular target subnuclei of the IPN in both perinatal and adult hosts, and restore ChAT staining in the IPN of perinatal hosts. Similarly placed transplants of fetal thalamus cells only restore ChAT staining in the IPN of adult hosts. In this study, we examined the functional significance of these restored staining patterns. We used a behavioral measure of the integrity of REM-stage and non-REM-stage sleep, the "flower pot" test, and assayed (1) normal adult rats, (2) FR-lesioned control animals (neonatal or adult operates), (3) animals receiving FR lesions and transplants of fetal habenula cells (perinatal or adult hosts), and (4) animals receiving FR lesions and transplants of fetal thalamus cells (adult hosts). FR lesions decrease markedly the muscle atonia component of REM sleep and reduce duration of sleep episodes. Transplants that restore SP staining in the IPN (habenular transplants into either perinatal or adult lesion hosts) restore normal frequency of REM atonia; transplants that restore ChAT staining (habenular transplants into perinatal hosts or thalamic transplants into adult hosts) restore normal duration of sleep episodes. The number of SP-immunoreactive cells in the transplants predicts recovery of REM atonia, and the number of ChAT cells in habenular (but not thalamic) transplants predicts restoration of sleep duration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Different populations of dorsal lateral geniculate nucleus neurons have concentration-specific requirements for a cortically derived neuron survival factor.

A macromolecular fraction of conditioned culture medium (CM) derived from explant cocultures of embryonic rat posterior cortex and caudal thalamus is able to support the survival of neurons in the dorsal lateral geniculate nucleus (dLGN) of newborn rats following ablation of dLGN cortical target areas. In the present study we tested whether the survival-promoting activity of this target-derived neurotrophic agent was concentration dependent and whether different subpopulations of dLGN neurons were equally responsive. With the starting concentration of the CM fraction designated X, increasing concentration results in a progressive falloff in trophic activity so that at 200X overall dLGN survival is similar to that seen in unconditioned medium (UM) controls. In contrast, diluting the fraction produces an increase in activity until maximal survival is achieved at 0.2X. Further dilutions result in a decline in trophic activity until control values are reached at 0.001X. Two populations of neurons within the dLGN, defined by their time of origin, respond in a specific manner to the different concentrations. Neurons generated during the early stages of neurogenesis (E14) have maximal survival (25.8%) at 0.05X, whereas those neurons generated later (E15/16) are maximally supported (30.7% survival) at 10X, a 200-fold difference in concentration. While it is possible that separate neurotrophic and neurotoxic molecules exist for each of these populations of dLGN neurons, the most parsimonious interpretation of the data is that a single cortically derived neurotrophic factor exists whose production is strictly controlled during development to achieve maximal effect on different populations of thalamic neurons that may be functionally distinct.

Animals↗
PubMed1989

Neurotrophic and behavioral effects of occipital cortex transplants in newborn rats.

Cell suspensions of embryonic occipital cortex were transplanted into newborn rats with large unilateral visual cortex lesions. When the animals were adults, they were tested on a difficult visual discrimination, and subsequently their brains were analyzed for possible neurotrophic effects of the transplants on nonvisual cortical areas which normally form connections with the occipital cortex. Behaviorally, animals with lesions and transplants learn to discriminate between columns and rows of squares at a rate which is identical to normal rats while animals with lesions and no transplants are impaired. Volume and cell-density measures show that the transplants also rescue neurons in cortical area 8 that would normally degenerate following the cortical lesion. No such neurotrophic effect of the transplants is found in cortical area 24 or area 17 contralateral to the lesion. In rats with lesions and no transplants, there is a significant correlation between the amount of area 8 remaining after the lesion and trials to criterion on the columns-rows discrimination, a relationship that does not exist in transplant animals because of their normal learning curve and the consistent sparing of area 8. Injections of HRP into the visual cortex contralateral to the lesion result in variable numbers of labeled cells within the transplant. However, there is no consistent relationship between the number of transplant cells which project to the opposite hemisphere and learning of the discrimination. It is suggested that the learning deficit following the lesion is largely attentional and that the sparing of cortical area 8 (which in rats may include the analog of the frontal eye fields present in the primate cortex) contributes to the sparing of function.

Animals↗
PubMed1987

Diffusible proteins prolong survival of dorsal lateral geniculate neurons following occipital cortex lesions in newborn rats.

Removal of the occipital cortex in newborn rats results in the rapid and nearly complete degeneration of the dorsal lateral geniculate nucleus (dLGN) in 5 days. In previous studies we have shown that transplants of embryonic posterior cortex neurons, which are allowed to develop in culture for 5 days prior to transplantation into the site of the lesion, prolong the survival of a particular population of host dLGN neurons for an additional week. In this study we tested the possibility that the transplant cells synthesize diffusible proteins which are responsible for this neurotrophic effect. Culture medium conditioned by explants of embryonic occipital cortex and diencephalon was concentrated by vacuum dialysis or ultrafiltration through membranes with at least a 10-kDa cut-off. This concentrated medium was loaded into polyacrylamide or sodium alginate gels which were then implanted into the cavity of the lesion. Five days after implantation, the alginate-conditioned-medium implants result in a 3-fold increase in dLGN survival compared to unconditioned medium controls, while a two-fold increase in survival of the nucleus is found with the polyacrylamide-conditioned-medium implants. Proteolysis of the conditioned medium eliminates all neurotrophic activity. The results suggest that the death of dLGN neurons following the cortical lesion is due to the loss of diffusible proteinaceous neurotrophic factors--factors that may operate during normal in vivo development of the geniculocortical pathway.

Animals↗
PubMed1987

Specific neurotrophic interactions between cortical and subcortical visual structures in developing rat: in vivo studies.

The specificity of trophic interactions in the rat visual system is investigated in vivo by using a combination of tissue culture and CNS transplantation methods. In a companion paper (Repka and Cunningham: '87) we showed that explants of embryonic day 14 (E14) occipital cortex are biased to contain different cortical cell populations depending on whether the explants develop in culture with diencephalon or with optic tectum. In this study we transplanted these precultured cortical explants into the cavity created by a lesion of the occipital cortex in newborn rats and then measured the neuron-occupied volume and the numbers of thymidine-labeled cells in the surviving ipsilateral dorsal lateral geniculate nucleus (dLGN) of the host rats. The results were compared to animals with lesions but no transplants, animals with transplants of E14 cortical tissue that had not been precultured, and animals with cerebellar transplants that had been similarly precultured either with other cerebellar tissue or with diencephalon. At 5 days postlesion, both the largest dLGN volume and the greatest number of labeled dLGN neurons survive in animals with cortical transplants precultured with diencephalon or other cortex. The surviving dLGN neurons that are rescued by these transplants are generated on E15 or E16, a period that corresponds to the latter part of geniculate neurogenesis. Relatively few cells generated on E14 survive in any group of animals. Furthermore, animals with all types of cortical transplants have significantly larger volumes of surviving dLGN than animals with either lesions only or cerebellar transplants.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Cortical transplants reveal CNS trophic interactions in situ.

Five days after transplanting fetal rat posterior cortex into newborn host rats with posterior cortex lesions, the host's dorsal lateral geniculate nucleus (dLGN) contains 2-5 times as many neurons as the dLGN of lesion-only controls. This effect is temporary and restricted to neurons created later in dLGN neurogenesis. Similar transplants of cerebellar plate are ineffective. These findings suggest that intracranial transplants of CNS tissue can be a source of specific trophic support to particular host neurons.

Animals↗
PubMed1982

[Scanning electron microscope demonstration of wall colonization of water-bearing plastic tubes].

A polyethylene and a silicone tube from water leading system of a dental unit, in which Pseudomonas aeruginosa could be isolated, were investigated by S.E.M. (Scanning Electron Microscopy). In the tubes thick deposits of extracellular material were found, in which microorganisms were embedded or on which they were free-lying. Pretreatment of the water systems by irrigating and by disinfection was unsuccessful. The possible protection of microorganisms by the demonstrated extracellular material against hydraulic forces and disinfection is discussed.

Adhesiveness↗