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Biomedical subjects

L A Shapiro

Publications and source records attributed to L A Shapiro.

At least 19 recordsLinked to original sources
PubMed2005

Newly generated dentate granule cells from epileptic rats exhibit elongated hilar basal dendrites that align along GFAP-immunolabeled processes.

Previous studies showed that neurogenesis occurs in the dentate gyrus of the adult rodent. Recent evidence suggests that the resulting newly born neurons integrate into pre-existing hippocampal circuitry. Newly born neurons in the developing and adult dentate gyrus exhibit a transient basal dendrite. In adult pilocarpine-induced epileptic rats, basal dendrites persist and are ectopically located in the hilus where they receive synaptic input from mossy fiber axons. We hypothesize that these hilar basal dendrites are derived from newly born neurons that are born after the pilocarpine-induced seizures. To test this hypothesis, the length of basal dendrites from epileptic rats was compared with that from control rats using doublecortin immunocytochemistry, which labels newly born neurons and their processes for up to 3 weeks after their genesis. The data on hilar basal dendrites in pilocarpine animals indicate that those from newly born neurons are significantly longer than those found in the control rats. We also demonstrate that 20% of newly born neurons in the epileptic rat have a basal dendrite that enters the hilus at an angle greater than 30 degrees from its cell body as compared with <2% in the control rats. Lastly, we provide evidence that the hilar basal dendrites in the epileptic rats are adjacent to glial fibrillary acidic protein-labeled astrocytic processes in the hilus and suggest that an ectopic glial scaffold in the hilus is involved with the formation of hilar basal dendrites. In conclusion, the data show that newly born neurons from epileptic rats have longer hilar basal dendrites and their formation might relate to gliosis which occurs as a result of hilar neuronal cell loss after status epilepticus.

Animals↗
PubMed1998

Increase in serotonin-1A autoreceptors in the midbrain of suicide victims with major depression-postmortem evidence for decreased serotonin activity.

It has been hypothesized that a deficit in serotonin may be a crucial determinant in the pathophysiology of major depression. Serotonin-1A receptors are located on serotonin cell bodies in the midbrain dorsal raphe (DR) nucleus, and the activation of these receptors inhibits the firing of serotonin neurons and diminishes the release of this neurotransmitter in the prefrontal cortex. Repeated treatment with some antidepressant medications desensitizes serotonin-1A receptors in the rat midbrain. The present study determined whether the binding of [3H]8-hydroxy-2-(di-n-propyl)aminotetralin (8-OH-DPAT), an agonist at serotonin-1A receptors, is altered in the midbrain of suicide victims with major depression. Radiolabeling of the serotonin-1A receptor in the DR varied significantly along the rostral-to-caudal extent of the human midbrain. The binding of [3H]8-OH-DPAT to serotonin-1A receptors was increased significantly in the midbrain DR of suicide victims with major depression as compared with psychiatrically normal control subjects. In suicide victims with major depression, the increase in the binding of [3H]8-OH-DPAT to serotonin-1A receptors was detected in the entire DR and specifically localized to the dorsal and ventrolateral subnuclei. Enhanced radioligand binding of an agonist to inhibitory serotonin-1A autoreceptors in the human DR provides pharmacological evidence to support the hypothesis of diminished activity of serotonin neurons in suicide victims with major depression.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1997

Serotonin receptors in suicide victims with major depression.

Serotonin1A (5-HT1A) and serotonin2A (5-HT2A) receptors in the brain have been implicated in the pathophysiology of suicide. Brain samples were collected at autopsy from suicide victims with a current episode of major depression and matched comparison subjects who died of natural or accidental causes. Retrospective psychiatric assessments were collected from knowledgeable informants for all suicide victims and most of the comparison subjects. Psychiatric diagnoses were determined according to DSM-III-R criteria. Any subjects with current psychoactive substance use disorders were excluded. Quantitative receptor autoradiography was used in serial sections of the right prefrontal cortex (area 10) and hippocampus to measure the binding of [3H]8-hydroxy-2-(di-n-propyl)-aminotetralin ([3H]8-OH-DPAT) to 5-HT1A receptors and [3H]ketanserin to 5-HT2A receptors. Analysis of covariance was used to compare control subjects and suicide victims with major depression. The age of subjects, the time from death to freezing the tissue (postmortem interval), and the storage time of tissues in the freezer were used as covariates in the analyses. There were no significant differences between suicide victims with major depression and comparison subjects in 5-HT1A or 5-HT2A receptors in area 10 of the right prefrontal cortex or the hippocampus. The current results suggest that the number of 5-HT1A and 5-HT2A receptors in the right prefrontal cortex (area 10) or hippocampus are not different in suicide victims with major depression.

Adult↗
PubMed1996

Quantitative subregional distribution of serotonin1A receptors and serotonin transporters in the human dorsal raphe.

Subregional distributions of serotonin1A receptors and serotonin transporters within the human dorsal raphe nucleus (DR) were determined by quantitative autoradiographic analyses of radioligand binding in tissue sections. [3H]8-Hydroxy-2-(di-n-propyl)aminotetralin (8-OH-DPAT) and [3H]paroxetine were used to label, respectively, serotonin1A receptors and serotonin transporters in the subnuclei of the DR, which were delineated on the basis of tryptophan hydroxylase (TrpOH) immunoreactivity. [3H]8-OH-DPAT binding was coextensive with the TrpOH-immunoreactive cell bodies and fibers but was distributed unevenly among the subnuclei. In contrast, [3H]paroxetine binding was present throughout the central gray matter, with relatively homogeneous labeling across the subnuclei of the DR. In rostral sections, [3H]8-OH-DPAT binding (fmol/mg protein) in the dorsal subnucleus was lower than that in the ventral or the interfascicular subnucleus. Within the interfascicular subnucleus, [3H]8-OH-DPAT binding decreased progressively in a rostral-to-caudal fashion. The highest levels of [3H]8-OH-DPAT binding were found in the ventrolateral subnucleus at the level of the caudal extent of the trochlear nucleus. The influence of age and postmortem interval on radioligand binding was also examined. These data in the human DR indicate that serotonin1A receptors are differentially distributed among the subnuclei and along the rostro-caudal axis of the midbrain raphe, and serotonin transporters appear to be relatively evenly distributed throughout the DR. Subregional analyses of such serotonergic markers may prove useful in evaluating the role that serotonin may play in depression, schizophrenia, and suicide.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1995

The effect of chronic treatment with a novel aryl-piperazine antipsychotic on monoamine receptors in rat brain.

The effects of chronic treatment of rats with RWJ 37796, a novel aryl-piperazine containing antipsychotic drug, on brain monoamine receptors were studied. Rats were treated daily with RWJ 37796 (1.3 mg/kg), the typical antipsychotic haloperidol (1 mg/kg) or vehicle (control) for 21 days, and were sacrificed 3 days after the last injection. Binding of [3H]Sch-23390 and [3H]spiperone to D1 and D2 dopamine receptors, respectively, and [3H]8-hydroxy-2-(di-n-propylamino)-tetralin ([3H]8OH-DPAT) to 5-HT1A receptors were measured in various brain regions using quantitative autoradiography. Binding to D2 dopamine receptors was significantly elevated in the caudate-putamen of rats treated with haloperidol or RWJ 37796 as compared to controls. However, the magnitude of the increase in D2 binding was significantly greater in haloperidol-treated (+38%) compared to RWJ 37796-treated (+21%) rats. Haloperidol treatment also increased binding (+35%) to D2 dopamine receptors in the nucleus accumbens, where RWJ 37796 treatment had a considerably smaller effect (+12). No changes in D1 dopamine or 5-HT1A receptor binding were detected following either antipsychotic treatment in any brain regions studied. Thus, at comparable doses, the novel antipsychotic RWJ 37796 produces less up-regulation of D2 dopamine receptor binding in the striatum than does the typical antipsychotic haloperidol.

Animals↗
PubMed1994

Repeated treatment with ascorbate or haloperidol, but not clozapine, elevates extracellular ascorbate in the neostriatum of freely moving rats.

Acute administration of neuroleptic drugs alters the extracellular level of ascorbate in the neostriatum, and increasing evidence suggests a role for this vitamin in the behavioral, and possibly therapeutic, effects of these drugs. To shed further light on this issue, extracellular ascorbate was recorded in the neostriatum and nucleus accumbens of awake, behaving rats following chronic treatment with either classical (haloperidol) or atypical (clozapine) neuroleptics or ascorbate itself. Electrochemically modified, carbon-fiber microelectrodes were lowered in place the day after the last of 21 daily injections of either haloperidol (0.5 mg/kg, SC), clozapine (20 mg/kg, IP), sodium ascorbate (500 mg/kg, IP) or vehicle. Voltammetric measurements were obtained during quiet rest and following administration of d-amphetamine (2.5 mg/kg). Repeated treatment with either haloperidol or ascorbate elevated basal extracellular ascorbate and potentiated the amphetamine-induced increase in ascorbate release in neostriatum but not nucleus accumbens. Both treatment groups also showed a significant increase in amphetamine-induced sniffing and repetitive head movements compared to vehicle-treated animals. In contrast, repeated clozapine had no effect on extracellular ascorbate in either neostriatum or nucleus accumbens, but increased the locomotor response to an amphetamine challenge. Thus, to the extent that increases in neostriatal ascorbate exert neuroleptic-like effects, such effects are likely to parallel haloperidol rather than clozapine.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1988

Protective effect of occlusion on disciform degeneration.

One patient developed disciform degeneration and loss of central vision despite laser application. Sixty-two years before, the contralateral eye had sustained a penetrating steel injury with subsequent scarring and pupillary membrane and cataract formation. This eye, when surgically rehabilitated, showed no signs of macular degeneration. Although alluded to, we know of no other known cases of occluded eyes being spared of senile macular degeneration reported in the literature. We postulate that unfiltered, ambient light may be the cause of macular degeneration and suggest that more emphasis should be placed on prevention of macular degeneration by the use of protective eye wear.

Aged↗
PubMed1987

[Activity of enzymes of glutathione metabolism and regulation by cAMP in human tumors].

Tumors were studied in 38 patients, tissues located far away from tumor being used as control. Breast and stomach tumors revealed relatively high levels of glutathione reductase, glutathione-S-transferase (I) and, particularly, gamma-glutamyl transferase (II). The said changes were not observed in colorectal tumors. Gamma-glutamyl transferase (II) may be used as a marker for breast and stomach malignancies in man but it is not a universal and absolutely specific marker for all tumors. The activity of glutathione peroxidase (III) either did not change or decreased. The activating effect of cAMP on III and I remained generally unchanged in all tumors studied.

Adult↗
PubMed1987

[Regulation by catecholamines and cAMP of enzymes of thiol and disulfide metabolism].

In vivo exo- and endogenous catecholamines have no influence on the activities of thioredoxin reductase, glutathione reductase, thiol transferase and nonselenium-dependent glutathione peroxidase. At the same time catecholamines activate via beta-adrenoceptors glutathione S-transferase and selenium-dependent glutathione peroxidase from many tissues and inhibit gamma-glutamyl transferase from kidney. In vitro cAMP has identical effects on the activities of the above enzymes. The possible significance of regulation of glutathione metabolism enzymes is discussed.

Adrenergic alpha-Agonists↗
PubMed1981

Single-injection epidural anesthesia with bupivacaine and morphine for prostatectomy.

In 30 patients having prostatectomies, 15 patients (group I) given single-injection epidural anesthesia using bupivacaine and morphine (4 mg) were compared with 15 patients (group II) given epidural bupivacaine without morphine. Patients in group I had pain relief for a mean duration of 27 hours and did not request additional analgesia. Patients receiving bupivacaine alone had pain relief for an average of 6.2 hours after surgery; all required narcotics postoperatively. It was concluded that the addition of 4 mg of morphine to the local anesthetic for epidural anesthesia in patients having prostatectomies results in excellent postoperative analgesia.

Aged↗
PubMed1977

Lipid keratopathy following corneal hydrops.

A case of lipid keratopathy occurred following acute rupture of Descemet membrane. The cause of the hydrops remained undetermined. There was no history of any prior corneal inflammation or vascularization in the initially involved eye. Lipid deposition was observed following resolution of the corneal edema, and its course was followed for the next several months. Histopathologic studies of the specimen showed lipid deposits in the posterior and middle corneal stroma and degenerative changes in the corneal lamellae and Bruch membrane. Laboratory examination disclosed a type IV hyperlipemia, with normal serum cholesterol levels and elevation of pre-beta-lipoproteins and triglycerides. It cannot be determined from our study if this condition was a causative factor.

Adult↗