PubMed Health⌕ Search

Biomedical subjects

D Albeck

Publications and source records attributed to D Albeck.

At least 19 recordsLinked to original sources
PubMed2000

Glial cell line-derived neurotrophic factor is essential for postnatal survival of midbrain dopamine neurons.

Glial cell line-derived neurotrophic factor (GDNF) is one of the most potent trophic factors that have been identified for midbrain dopamine (DA) neurons. Null mutations for trophic factor genes have been used frequently for studies of the role of these important proteins in brain development. One problem with these studies has been that often only prenatal development can be studied because many of the knockout strains, such as those with GDNF null mutations, will die shortly after birth. In this study, we looked at the continued fate of specific neuronal phenotypes from trophic factor knockout mice beyond the time that these animals die. By transplanting fetal neural tissues from GDNF -/-, GDNF +/-, and wild-type (WT) mice into the brain of adult wild-type mice, we demonstrate that the continued postnatal development of ventral midbrain dopamine neurons is severely disturbed as a result of the GDNF null mutation. Ventral midbrain grafts from -/- fetuses have markedly reduced DA neuron numbers and fiber outgrowth. Moreover, DA neurons in such transplants can be "rescued" by immersion in GDNF before grafting. These findings suggest that postnatal survival and/or phenotypic expression of ventral mesencephalic DA neurons is dependent on GDNF. In addition, we present here a strategy for studies of maturation and even aging of tissues from trophic factor and other knockout animals that do not survive past birth.

Animals↗
PubMed1999

Changes in brain nerve growth factor levels and nerve growth factor receptors in rats exposed to environmental enrichment for one year.

This study examined the effects of long-term differential rearing on levels of brain nerve growth factor, its receptors, and their relationships to cognitive function. Adult rats (two months old) were placed into either enriched or standard housing conditions where they remained for 12 months. Animals from the enriched condition group had significantly higher levels of nerve growth factor in hippocampus, visual and entorhinal cortices compared with animals housed in isolated condition. Immunohistochemical analysis of brain tissue from the medial septal area revealed higher staining intensity and fibre density with both the low-affinity and the high-affinity nerve growth factor receptors. Enriched rats performed better than isolated rats in acquisition of spatial learning and had lower locomotion scores in the open field. These results provide further evidence that experimental stimulation results in increased production of trophic factors and structural reorganization in specific brain regions known to be involved in cognitive function.

Age Factors↗
PubMed1998

A peptidergic basis for sexual behavior in mammals.

Vasopressin (VP) is a peptide neurotransmitter in the limbic system of rats. It is synthesized in the medial amygdaloid nucleus in the presence of sex steroids, transported to other limbic structures such as the hippocampus and septum and secreted there by a calcium-dependent process. In the hippocampus, VP acts on cerebral microvessels and local circuit interneurons. Its excitatory action on the inhibitory interneurons produces near-total shutdown of electrical activity of the efferent fibers of pyramidal cells, the projection neurons of the hippocampus. Stimulation of the medial amygdala and release of the endogenous VP duplicates these effects and, since they are blocked by ventricular application of a VP antagonist, the effects are almost certainly mediated by endogenous VP. Recording from the VP-containing cell bodies or of the hippocampal action of the peptide indicates that the system is selectively involved with the early stages of sexual behavior, specifically those appetitive behaviors that anticipate coitus. Stimulation of the VP cells produces alterations in sexual behavior in a manner consistent with the hypothesis that the medial amygdala organizes the appetitive phase of recognition of an appropriate partner and sexual arousal. This role for the medial amygdala complements the proposed role of nearby structures in the consummatory, reward and learned aspects of sexual behavior. Association between VP, oxytocin (OT) and homologs with sexual behavior is very widespread among vertebrates, including amphibians, reptiles, primates and humans. Humans and other primates display a phenomenon called 'concealed ovulation' that may have played a role in the evolution of social structures. The review concludes with a discussion of possible experimental strategies for evaluating the possible role of VP in concealed ovulation and other conditions in which sexual behavior occurs outside of estrus.

Animals↗
PubMed1998

A non-invasive system for delivering neural growth factors across the blood-brain barrier: a review.

Intraventricular administration of nerve growth factor (NGF) in rats has been shown to reduce age-related atrophy of central cholinergic neurons and the accompanying memory impairment, as well as protect these neurons against a variety of perturbations. Since neurotrophins do not pass the blood-brain barrier (BBB) in significant amounts, a non-invasive delivery system for this group of therapeutic molecules needs to be developed. We have utilized a carrier system, consisting of NGF covalently linked to an anti-transferrin receptor antibody (OX-26), to transport biologically active NGF across the BBB. The biological activity of this carrier system was tested using in vitro bioassays and intraocular transplants; we were able to demonstrate that cholinergic markers in both developing and aged intraocular septal grafts were enhanced by intravenous delivery of the OX-26-NGF conjugate. In subsequent experiments, aged (24 months old) Fischer 344 rats received intravenous injections of the OX-26-NGF conjugate for 6 weeks, resulting in a significant improvement in spatial learning in previously impaired rats, but disrupting the learning ability of previously unimpaired rats. Neuroanatomical analyses showed that OX-26-NGF conjugate treatment resulted in a significant increase in cholinergic cell size as well as an upregulation of both low and high affinity NGF receptors in the medial septal region of rats initially impaired in spatial learning. Finally, OX-26-NGF was able to protect striatal cholinergic neurons against excitotoxicity and basal forebrain cholinergic neurons from degeneration associated with chemically-induced loss of target neurons. These results indicate the potential utility of the transferrin receptor antibody delivery system for treatment of neurodegenerative disorders with neurotrophic substances.

Animals↗
PubMed1994

Activity of peptidergic neurons in the amygdala during sexual behavior in the male rat.

The medial amygdaloid nucleus (AME) occupies a central position in the circuitry that organizes sexual behavior in the male rat. It receives a projection from olfactory structures that are activated by pheromonal cues indicating receptivity in the female and projects in turn to limbic and hypothalamic structures that are thought to organize aspects of coitus. Electrical stimulation of the AME elicits a behavioral state that is indistinguishable by several measures from the post-ejaculatory interval. We used chronic single-unit recording techniques to determine the behavioral conditions in which the AME is normally active. We found that the cells indeed fired selectively during the presence of a receptive female, but that the discharge considerably anticipated copulation in time. We propose that sexual behavior in the male rat is a reaction chain of fixed action patterns, each one acting as a releaser for the next. The AME mediates an early event in the reaction chain, namely recognition of the receptive female, but electrical activation of the AME causes the reaction chain to proceed to its culminating behavior, the post-ejaculatory interval.

Amygdala↗
PubMed1993

Antidromic activation of a peptidergic pathway in the limbic system of the male rat.

Stimulation of the medial amygdaloid nucleus (AME) produces a long-latency and long-lasting inhibition of pyramidal cells in both the dorsal and the ventral hippocampus. The inhibition is blocked by a specific antagonist to vasopressin, which is a candidate neurotransmitter in the system. Antidromic activation of the AME from the hippocampus occurs with a latency suggestive of the conduction velocity of small diameter unmyelinated fibers. Immunocytochemistry for vasopressin reveals small diameter, unmyelinated immunoreactive fibers in the vicinity of the stimulating electrode in the hippocampus, and immunoreactive cell bodies in the vicinity of the recording electrode in the AME.

Amygdala↗
PubMed1992

A peptidergic circuit for reproductive behavior.

A projection from the medial amygdaloid nucleus to the hippocampus and septum probably uses vasopressin as a transmitter. The nucleus synthesizes vasopressin and activation of the nucleus has a hippocampal effect that is completely blocked by a vasopressin antagonist. The afferent and efferent projections of this peptidergic nucleus suggest a possible role for the system in sexual behavior. Stimulation of the nucleus inhibits the output of the hippocampus in both genders and reorganizes behavior for a period of 15-20 min. In males, the effect of peptidergic activation is to produce a behavior that resembles the post-ejaculatory interval in coitus. This state is characterized by an EEG that resembles slow-wave sleep and by ultrasonic vocalizations at a characteristic frequency of 22 kHz. Castration in either gender causes depletion of the peptide from the target fields and eliminates the peptidergic signal in the hippocampus after about 15 weeks. The effects of castration in males can be reversed by testosterone replacement. The fluctuation of estrogen levels in rat plasma during the estrus cycle happens too quickly to impact the peptidergic system, and thus there is no significant change in the strength of the peptidergic signal among the proestrus, estrus, metestrus and diestrus stages. This fact permits study of the physiology of the system without concern for stage of estrus but does not permit conclusions regarding its function in females.

Amygdala↗
PubMed1990

Peptidergic transmission in the brain. I. Vasopressin-like signal in the hippocampus.

Studies of the action of arginine vasopressin (AVP) in the rat hippocampal slice have produced a model of the peptide's neural action. AVP excites local circuit inhibitory interneurons and causes consequent inhibition of pyramidal cells that is apparent as a reduction in the amplitude of the evoked population spike in field potential recording. Here we show that applied AVP does the same thing to the evoked population spike in the whole animal. Then we show that stimulation of the source of hippocampampal AVP, the medial amygdaloid nucleus, also inhibits the evoked population spike. Analysis of the synaptic potential indicates that the same mechanisms are employed by exogenously applied and endogenously released peptide. The inhibition can only be obtained by stimulating those brain structures known to project vasopressin fibers to the hippocampus. The stimulus-response characteristics and kinetics of the endogenous signal correspond to the properties of peptidergic signals in simple systems. The results are taken to support a transmitter role for AVP in the rat hippocampus.

Action Potentials↗
PubMed1990

Peptidergic transmission in the brain. II. Mediation by a vasopressin-like peptide.

The medial amygdaloid nucleus (AME) sends a projection of fibers containing a peptide similar to arginine vasopressin (AVP) to the rat hippocampus. Electrical stimulation of the AME has an impact on evoked hippocampal field potentials that is identical to the effect obtained by applied AVP in vitro or in vivo. Here we show that the AVP-like peptide released by AME stimulation has action that is blocked by a structural AVP analog. The antagonist specificity suggests that the native transmitter is a peptide similar, but not identical, to AVP. We conclude that the AME projection to the hippocampus satisfies all the criteria for recognition as a central peptidergic system important in the generation of behavior.

Amygdala↗
PubMed1989

Microvascular spasm is mediated by vasopressin fibers in the rat hippocampal slice.

Microvessels in the rat hippocampal slice can be used as an in vitro model for the study of cerebral vasospasm. Serum from coagulated blood causes prompt and long-lasting microvascular constriction that is neurogenic in nature. Here we show that a candidate spasmogen, thromboxane B2, has excitatory action on neural elements in the slice. However, spasmogenic serum lacks this excitatory effect. Instead, it is inhibitory for a major population of slice neurons. Thus, neurogenic microvascular spasm is produced by a subpopulation of slice neurons or projection fibers, not all neurons acting in concert. Arginine vasopressin (AVP) is contained in fibers that project to the hippocampus, and hippocampal microvessels contain pressor (V1) receptors for the peptide. AVP causes vasoconstriction in the slice, and a specific V1 antagonist for the peptide blocks the microvascular spasm induced by blood serum. The results are interpreted to mean that neurogenic microvascular spasm is mediated by locally released AVP.

Animals↗
PubMed1988

A mechanism for vasopressin action in the hippocampus.

The action of arginine vasopressin (AVP) in the rat hippocampal slice has been extensively studied. Extracellular recording indicates that the peptide excites spontaneously active neurons in the slice, though uncertainty exists regarding the identity of this cell type. Intracellular recording from pyramidal cells also reveals an excitatory action of the peptide, but these results are confounded by simultaneous constriction of small blood vessels that surround each pyramidal cell. Here we use field potential recordings to show that AVP inhibits pyramidal cell discharge and employs a pressor-type (V1) receptor to bring about its action. The results resolve issues regarding the identity of AVP targets in the slice. Each reported result is consistent with a model that posits direct AVP excitation of inhibitory interneurons and direct AVP constriction of slice microvessels. Inhibition of pyramidal cells recorded extracellularly and excitation of pyramidal cells recorded intracellularly are respective indirect consequences of the two direct effects.

Animals↗
PubMed1987

Neurogenic mediation of serum-induced microvascular constriction.

We have used the rat hippocampal slice preparation as a model system for the study of microvascular vasospasm. Penetrating cerebral microvessels in the slice constrict in response to a variety of stimuli, including serum from coagulated blood. Microvascular responses to many stimuli are associated with changes in the activity of nearby neurons, and in some cases can be shown to be neurogenically mediated. Here we use the selective neurotoxin, tetrodotoxin (TTX), to show that serum-induced constriction is also neurogenically mediated. This neural regulation of microvessel caliber may participate in pathological vasoconstriction mechanisms in the whole animal.

Action Potentials↗
PubMedDate not supplied

Peptidergic transmission in the brain. VI. Behavioral consequences of central activation.

Having described a peptidergic transmitter system in the rat brain, we now begin to evaluate its behavioral function. We stimulated cell bodies in the medial amygdaloid nucleus (AME) with indwelling bilateral electrodes. These cell bodies contain a vasopressin-like peptide and send fibers to the hippocampus where the peptide is released upon stimulation. There the peptide inhibits hippocampal output in the awake rat just as it does in the anesthetized rat and in the rat brain slice. The stimulation reorganizes behavior with the same latency and duration as the hippocampal effect. For about 15-20 minutes after the brief stimulus, rats remain motionless with eyes wide open. This "freezing" state is punctuated by episodes of exploratory behavior. The stimulus appears to have a positive affective quality. Review of the literature in light of the present results indicates a probable role for this peptidergic system in the generation of sexual behavior in male rats.

Amygdala↗
PubMedDate not supplied

Peptidergic transmission in the brain. V. Systemic correlates of central activation.

Inhibition of the hippocampus by the medial amygdala is mediated by vasopressin-like peptide. Because vasopressin has action on the periphery as well as the brain, we conducted experiments to evaluate the relationship between possible peripheral actions and the central effects of the endogenous peptide. In the acutely anesthetized rat, peptide-mediated inhibition of the hippocampus is not associated with significant changes in heart rate, blood pressure or body temperature. Peripheral injections of peptide agonist fail to evoke the central inhibition, and peripheral injections of peptide antagonist fail to block the central inhibition. Stimulation of central nuclei that contain vasopressin or a similar peptide also fail to duplicate the effect of stimulating the amygdala. We conclude that the peptidergic transmission is independent of peripheral causes or correlates.

Amygdala↗
PubMedDate not supplied

Peptidergic transmission in the brain. III. Hippocampal inhibition by the amygdala.

The mechanism of arginine vasopressin (AVP) action in the rat hippocampus has been determined. The peptide activates inhibitory interneurons and constricts cerebral microvessels. In the whole animal, each of these direct actions has secondary consequences for the excitability of pyramidal cells. Recent studies have shown that a peptide similar to AVP mediates endogenous neurotransmission in the hippocampus. Here we report experiments showing that the endogenous peptide activates the same mechanisms as exogenously applied AVP. The endogenous AVP-like peptide has no effect on the presynaptic fiber volley, or on pure somatic and dendritic postsynaptic potentials. These results are taken to exclude presynaptic mechanisms as explanations for the peptide's action. The endogenously released peptide inhibits individual pyramidal cells in single unit recording and excites presumed interneurons, just as AVP itself is known to act. The endogenous peptide is released only by stimuli applied to a nucleus that contains immunoreactive AVP and projects to the hippocampus.

Amygdala↗