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Biomedical subjects

N J Lenn

Publications and source records attributed to N J Lenn.

At least 19 recordsLinked to original sources
PubMed1998

Symptoms of depression and anxiety in pediatric epilepsy patients.

PURPOSE: We assessed rates of symptoms of anxiety and depression among pediatric patients with epilepsy. METHODS: We administered the Revised Child Manifest Anxiety Scale (RCMAS), and Child Depression Inventory (CDI) to 44 epilepsy patients aged 7-18 years (mean age 12.4 years). Demographic, socioeconomic, and epilepsy-related information was examined in relation to depression and anxiety scores. RESULTS: No patients had been previously identified to have depression or anxiety. However, 26% had significantly increased depression scores and 16% met criteria for significant anxiety symptomatology. CONCLUSIONS: Symptoms of depression and anxiety are common among pediatric patients with epilepsy and appear to be overlooked by care providers.

Adolescent↗
PubMed1995

Differential spatiotemporal expression of K+ channel polypeptides in rat hippocampal neurons developing in situ and in vitro.

Hippocampal neurons are highly plastic in their excitable properties, both during development and in the adult brain. As voltage-sensitive K+ channels are major determinants of membrane excitability, one mechanism for generating plasticity is through regulation of K+ channel activity. To gain insights into the regulation of K+ channels in the hippocampus, we have analyzed the spatiotemporal expression patterns of five K+ channel polypeptides in rat hippocampal neurons developing in situ and in vitro. Delayed rectifier-type channels (Kv1.5, Kv2.1, and Kv2.2) are expressed on all neuronal somata and proximal dendrites, while A-type channels (Kv1.4 and Kv4.2) are present distally on distinct subpopulations of neurons. The development of these patterns in situ is monotonic; that is, while the time and spatial development varies among the channels, each K+ channel subtype initially appears in its adult pattern, suggesting that the mechanisms underlying spatial patterning operate through development. Immunoblots confirm the differential temporal expression of K+ channels in the developing hippocampus, and demonstrate developmentally regulated changes in the microheterogeneity of some K+ channel polypeptide species. Temporal expression patterns of all five K+ channels observed in situ are retained in vitro, while certain aspects of cellular and subcellular localization are altered for some of the K+ channel polypeptides studied. Similarities in K+ channel polypeptide expression in situ and in vitro indicate that the same regulatory mechanisms are controlling spatiotemporal patterning in both situations. However, differences between levels of expression for all subtypes studied except Kv2.1 indicate additional mechanisms operating in situ but absent in vitro that are important in determining polypeptide abundance.

Aging↗
PubMed1995

TrkA expression in the CNS: evidence for the existence of several novel NGF-responsive CNS neurons.

NGF acts as a neurotrophic factor by binding and activating its receptor on certain neuronal populations in the CNS and PNS. TrkA is a receptor for NGF. Recent findings in vitro indicate that this NGF-activated receptor tyrosine kinase transduces the NGF signal. To further define NGF actions in the CNS, we examined trkA expression in the adult rat brain. We found that trkA mRNA and immunoreactivity (IR) coincided in specific, defined neuronal populations in the forebrain and brainstem. In addition to cholinergic neurons in the basal forebrain and neostriatum, trkA expression was found in noncholinergic neurons in (1) the paraventricular anterior and reuniens thalamic nuclei, (2) the rostral and intermediate subnuclei of the interpeduncular nucleus (IPN), (3) scattered neurons in the ventrolateral and paramedian medulla, (4) the prepositus hypoglossal nucleus, and (5) the area postrema. NGF responsiveness was demonstrated for each of these populations. In contrast to trkA, p75NGFR was found only in a minority of NGF-responsive populations. Our data provide further evidence that expression of trkA marks NGF-responsive CNS neurons and suggests novel roles for NGF in the brain.

Animals↗
PubMed1994

Dopaminergic regulation of a transfected preproenkephalin promoter in primary rat astrocytes in vitro and in vivo.

The clinical benefit of transplantation therapies utilizing genetically modified cells could be enhanced if expression of engineered genes was regulated by clinically useful pharmacological agents. Toward this end, we examined pharmacologic effects on the expression of hybrid gene constructs transfected into primary rat striatal astrocytes. These astrocytes are known to express receptors for the neurotransmitter dopamine (DA). In vitro, we found that expression of a transiently transfected human ppEnk promoter-driven chloramphenicol acetyltransferase (CAT) reporter construct was induced by DAergic agonists, as much as 20-fold. This induction was blocked by a DA receptor antagonist. The same concentration of DA also increased the endogenous rat ppEnk mRNA, by > 2-fold. In vivo, regulation of CAT expression by DA was tested by implanting the genetically modified astrocytes into the normal striatum and the contralateral striatum which had > 95% DA depletion induced by a previous 6-hydroxy-DA lesion of the substantia nigra. As hypothesized on the basis of the in vitro data, CAT activity on the lesioned side, where the stimulating effect of endogenous DA was lacking, was 30% lower than on the control side where the normal DA content was present. The data suggest that control of the enkephalin gene in astrocytes may involve second messenger pathways activated by DA receptors. Moreover, the evidence that clinically applicable drugs can regulate inducible genes introduced into the brain by astrocyte implantation is of potential importance in development of therapeutic strategies.

Animals↗
PubMed1993

Chronic paroxysmal hemicrania in a young child: possible relation to ipsilateral occipital infarction.

We report a child with chronic paroxysmal hemicrania beginning at 3 years of age with more than 2 years of daily episodes. Indomethacin produced total relief. An ipsilateral, occipital hemorrhagic infarction, probably predating the headaches, may have contributed to their pathogenesis. This is an unusually early onset and persistent chronic paroxysmal hemicrania of possible symptomatic type.

Cerebral Infarction↗
PubMed1992

Clinical utility of unbound antiepileptic drug blood levels in the management of epilepsy.

We tabulated all unbound and total antiepileptic blood levels collected in 13 months. According to strict criteria, 24% of phenytoin and 15% of valproate unbound blood levels but none of the carbamazepine unbound levels had clinical significance in the management of seizures or side effects. These data support frequent use of unbound phenytoin or valproate blood levels in the management of epilepsy.

Anticonvulsants↗
PubMed1990

The hippocampus in experimental chronic epilepsy: a morphometric analysis.

The effect of intermittent seizures on the pyramidal neurons of the hippocampus is largely unknown. To determine whether recurrent seizures centered in the hippocampus can produce neuronal loss in this region, a morphometric analysis was performed from standardized sections of hippocampus using 5 groups of animals: (1) surgical control subjects, (2) rats kindled by the rapidly recurring hippocampal seizure (RRHS) paradigm, (3) kindled rats with a few additional limbic seizures (528 +/- 66 seizures), (4) kindled rats with many limbic seizures (1,523 +/- 130 seizures), and (5) rats experiencing limbic status epilepticus (SE) induced by "continuous" hippocampal stimulation. The RRHS and SE protocols induced significant neuronal loss in the CA1 region, but no evidence was found for additional cell loss with increasing numbers of intermittent seizures. These intermittent seizures were, however, associated with a significant thickening of the basal and apical dendritic fields of the CA1 region. These findings indicate that intermittent seizures produce no significant hippocampal neuronal loss and may result in a hypertrophy of CA1 dendritic fields.

Animals↗
PubMed1990

Hemicholinium-3 binding sites in subnuclei of the rat interpeduncular nucleus: quantitative in vitro autoradiography.

The interpeduncular nucleus (IPN) receives dense cholinergic input from the medial habenulae (MH) via the fasciculus retroflexus (FR). This projection is known to terminate in the rostral, central and intermediate subnuclei. Correspondingly, the concentration of hemicholinium-3 (HC-3) binding sites in these subnuclei was equal to or greater than that reported in any other brain areas. Moderate values in the distal FR and in the lateral subnuclei indicate that choline uptake sites are located on nonterminal portions of MH afferent axons as well. Possible relationships of HC-3 binding to the unusual metabolic properties of FR and IPN, and to the distribution of choline acetyltransferase-containing axons and terminals in FR and IPN are suggested.

Animals↗
PubMed1989

Modification of left-right pairing during the development of individual crest synapses in the rat interpeduncular nucleus.

The synaptic organization of the rat interpeduncular nucleus is highly ordered in the normal adult. By 90 days of age, 90% of crest synapses in its intermediate subnuclei are formed by two cholinergic endings, one from each medial habenula. Stereological calculation of the number of crest synapses per intermediate subnucleus, based on total samples of crest synapses in 3-4 sections through the subnucleus, allows comparisons of afferent pairing among ages without interference by other developmental changes. Between 21 and 90 days of age, the total number of crest synapses per intermediate subnucleus increases tenfold (p less than 10(-8], from 90,000 at 21 days of age, through 130,000 at 28 days, 440,000 at 45 days, to 1,000,000 at 90 days. The volume of the intermediate subnucleus increases fivefold during the same interval. Electron microscopic degeneration was used to estimate the pairing of left and right habenula afferents at crest synapses at the same ages. Through 21 days of age, only one-third of crest synapses are formed with pairing of one left and one right medial habenula afferent, whereas two-third have both afferent endings arising from the same medial habenula. At 28 days of age left-right pairing has increased to 43%, and at 45 days of age 53%, or 240,000, are so paired. The number of same-side paired crest synapses at 45 days, 210,000, is 3.5 times the number so paired at 21 days (p = .003). This indicates continued formation of considerable numbers of crest synapses with this transient mode of airing as late as 45 days of age.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1989

Fetal medial habenula transplants: innervation of the rat interpeduncular nucleus.

The effects of donor age and site of placement on the survival of fetal medial habenula (MH) transplants into adult rats hosts were examined. The innervation of the interpeduncular nucleus (IPN) in such cases was also examined. Explants of MH consisting of the medial-dorsal lip of the third ventricle were held in vitro for 1-2 days. Colloidal gold conjugated to wheat germ agglutinin was added for the last 18 hours to label the cells. Four of 16 cases with E19 derived transplants contained donor neurons. Markedly larger transplants were present in 95% of 20 cases with E16 derived transplants. Sites in the ventral midbrain were successful, while limited or no survival occurred at sites more remote from IPN. Retrograde labeling of transplant neurons was present in each case studied with HRP injection into host IPN. Colloidal gold-labeled macrophages, some oriented capillaries and GFAP-positive processes marked the donor-host interface. In EM the interface was evident only by the difference in tissue elements in the transplant versus host. Numerous synapses of Gray types I and II were present in the transplant. Excellent survival of MH neurons, donor/host interfaces, innervation of IPN by the transplant and fine structure in and around the transplants, all suggest that such preparations are suitable for further experimental analysis of the habenulo-interpeduncular system.

Animals↗
PubMed1988

Behavioral and metabolic alterations in the opiate withdrawal syndrome induced by lesions of fasciculus retroflexus.

The interpeduncular nucleus (IPN) appears to be an important integrative center within the limbic system based on its extensive afferent and efferent connections and the presence of numerous neurotransmitters and peptides. Opiate receptors are present within particular subregions of IPN, which is one of the limbic structures showing an increase in regional glucose utilization (RGU) during withdrawal of morphine-addicted rats. The possible role of neural connections in withdrawal was studied by lesioning the main afferent pathway to IPN, the fasciculus retroflexus (FR) bilaterally. Four subnuclei of IPN, lateral, central, rostral and intermediate and FR showed significantly smaller increases in RGU during naloxone-induced withdrawal when compared to sham-operated controls. No difference was found in the apical, dorsal medial or dorsal lateral subnuclei. This metabolic effect of the lesions is not related in any simple way to the localization of opiate receptors or other neurochemical features of IPN. The lesioned animals also had greater weight loss due to diarrhea during withdrawal, consistent with IPN's presumed connection to the vagal nuclei. IPN appears to exhibit local and independent effects of FR lesions during opiate withdrawal.

Animals↗
PubMed1987

Neuroplasticity and the developing brain: implications for therapy.

Normal brain development consists of a series of interdependent and temporally overlapping processes. These include cell division, migration and aggregation, dendritic elaboration, axonal elongation and arborization, and synaptogenesis. There is a general pattern in all of these of predictable early development with evidence of specificity, followed by a period of remodeling. Lesions of the central nervous system occurring during development will affect these developmental processes at different points in the sequence and therefore have disparate effects on different portions of the brain at any given time of occurrence, as well as different effects depending on the time when the insult occurs. Unlike lesions occurring in the more steady-state condition of the adult nervous system, lesions during development have additional effects in redirecting subsequent development. It is arguable that this implies enhanced opportunities to mitigate the deleterious effects of such lesions. Potential therapeutic interventions can be divided by whether they are applied acutely, subacutely or late after injury. There are reasons for optimism regarding development of powerful new treatments in each of these categories. Further delineation of plasticity and the application of the resulting insights promise exciting and therapeutically important advances.

Animals↗
PubMed1986

Auditory processing deficit in a patient with Rett syndrome.

Because of the consistent and prominent language failure in Rett syndrome, a patient with the characteristic phenotype was tested for subtle auditory processing deficits by visual reinforcement audiometry. In spite of excellent detection threshold and frequency discrimination, frequency sweep discrimination was at a chance level. This discrimination is normally performed by 5-8 month old infants. This observation suggests a defect in the specialized units of the inferior colliculus or higher auditory centers which subserve frequency sweep discrimination.

Audiometry↗
PubMed1986

Neurogenesis in subnuclei of the rat interpeduncular nucleus and medial habenula.

Development of the rat habenulo-interpeduncular system is of interest because of its highly ordered adult structure, including seven subnuclei within the interpeduncular nucleus (IPN), localization of synapses of different types and medial habenular (MH) sites of origin within the subnuclei, and differential localization of neurochemicals amongst the subnuclei. In order to further investigate the mechanisms by which these features are produced, the birthdays of neurons within IPN and MH were investigated. All IPN neurons were formed on embryonic days (E) 12 to 16. Birthdays varied for the subnuclei of IPN with the earliest being the serotonin containing apical subnucleus (p less than 0.0001) and the latest being the rostral subnucleus (p less than 0.0001). Rostral lateral and lateral subnuclei were approximately simultaneous with apical, and the intermediate and central subnuclei, related to each other in a number of other ways, had simultaneous birthdays earlier than the rostral subnucleus (p less than 0.0001) and later than the other subnuclei (p less than 0.0001). The medial habenula was found to consist of three regions, termed medial, lateral and dorsal, whose neurons undergo their final mitoses on E15-16, 16-17 and 17-18, respectively. These findings provide additional support for the validity of IPN subnuclei as currently delineated. They suggest mechanisms of development which involve early interactions between specific groups of MH neurons and specific groups of IPN neurons. It is proposed that a sequence of several control mechanisms operates during development to produce this complex system.

Animals↗