PubMed Health⌕ Search

Biomedical subjects

Nader D Halim

Publications and source records attributed to Nader D Halim.

4 recordsLinked to original sources

A novel ELISA using PVDF microplates.

Here we describe the development of a novel specific, rapid ELISA system, which is performed on modified microplates where polyvinylidine fluoride (PVDF) forms the base of each well. The use of microplates with PVDF membranes as the solid phase allows for a greater binding capacity of protein in comparison to the solid phases of traditional ELISAs. The increased binding capacity of the solid phase provides for the direct binding of antigens, which can subsequently be assayed using a single, specific and well-characterized antibody. This direct assay system eliminates the need for two distinct antibodies that are often necessary in conventional two site ELISA systems. The system is able to specifically detect purified proteins as well as antigens in crude preparations of tissue homogenates. The PVDF-based ELISA performs with similar sensitivity and reproducibility as conventional two site ELISAs in tissue homogenates. The intra- and inter-assay coefficients of variation for the measurement of actin in crude rat brain homogenate were 2.36 and 5.15%, respectively.

Actins↗

Effects of chronic haloperidol and clozapine treatment on neurogenesis in the adult rat hippocampus.

It has been proposed that the therapeutic benefits of treatment with antidepressants and mood stabilizers may arise partially from their ability to stimulate neurogenesis. This study was designed to examine the effects of chronic antipsychotic treatment on cell proliferation and survival in the adult rat hippocampus. Haloperidol (0.05 and 2 mg/kg), clozapine (0.5 and 20 mg/kg), or vehicle were administered i.p. for 28 days, followed by bromodeoxyuridine (BrdU, 200 mg/kg, i.p.), a marker of DNA synthesis. One group of rats was killed 24 h following BrdU administration and BrdU-positive cells were quantified to assess the effects of drug treatment on cell proliferation. The remaining animals continued on antipsychotic medication for an additional 3 weeks following BrdU administration to assess the effects of antipsychotics on cell survival. Our results show that 24 h following BrdU, a low dose of clozapine (0.5 mg/kg) increased the number of BrdU-positive cells in the dentate gyrus (DG) by two-fold. Neither 20 mg/kg of clozapine nor haloperidol had any effect on cell proliferation in DG. Moreover, neither drug at either dose had an effect on the number of newly generated neurons surviving in the DG 3 weeks following BrdU administration. These preliminary findings suggest that clozapine may influence the number of cells which divide, but antipsychotics do not promote the survival of the newly generated neurons at 3 weeks after a BrdU injection.

Analysis of Variance↗

Behavioral effects of neonatal and adult excitotoxic lesions of the mediodorsal thalamus in the adult rat.

We examined in the rat, the effects of neonatal (postnatal Day 7) and adult excitotoxic lesions of the mediodorsal thalamus (MDT), a brain area innervating the prefrontal cortex and implicated as a site of neuropathology in schizophrenia. Previous studies showed that rats with neonatal excitotoxic damage of the ventral hippocampus (VH), used as an animal model of this disorder, display in young adulthood a variety of abnormalities reminiscent of schizophrenia, including hyperactivity to stressful stimuli and amphetamine. It has been speculated that behavioral abnormalities of the neonatally VH lesioned animals are mediated through MDT projections to the prefrontal cortex. We tested if rats with ibotenic acid (1.5 microg per hemisphere in neonates, 2 microg in adults) lesions of MDT exhibited motor hyperactivity in the same experimental conditions (i.e. in response to novelty, saline injections and amphetamine administration) as rats with the VH lesions. We found that, in contrast to rats with VH lesions, neonatally lesioned MDT rats showed reduced vertical activity in response to amphetamine and no changes in locomotor activity to novelty, saline or amphetamine injections 7 weeks postlesion. Adult lesioned MDT rats exhibited no changes in motor activity as compared to controls at 7 weeks postlesion. These results indicate that neonatal or adult excitotoxic lesions of MDT do not produce behavioral changes analogous to those seen after neonatal VH lesions and do not appear to reproduce animal model-like features of schizophrenia.

Aging↗

Effects of reversible inactivation of the neonatal ventral hippocampus on behavior in the adult rat.

Rats with neonatal excitotoxic damage of the ventral hippocampus display in adulthood a variety of abnormalities reminiscent of schizophrenia and are used as an animal model of this disorder. In the present study, we hypothesized that transient inactivation of ventral hippocampal activity during a critical developmental period may be sufficient to disrupt normal maturation of relevant brain systems and produce similar lasting behavioral changes. We infused tetrodotoxin (TTX) or artificial CSF into the ventral hippocampus on postnatal day 7 (P7) and assessed behavioral changes in response to stress, amphetamine, and (+)-5-methyl-10,11-dihydro-5H-dibenzo [a,d] cyclohepten-5,10-imine maleate in juvenile (P35) and young adult (P56) rats. In adulthood, rats infused neonatally with TTX displayed motor hyperactivity after pharmacological stimulation and after stress compared with sham controls. Analogous TTX infusions in adult animals did not alter these behaviors later in life. These data suggest that transient loss of ventral hippocampal function during a critical time in maturation of intracortical connections permanently changes the development of neural circuits mediating certain dopamine- and NMDA-related behaviors. These results represent a potential new model of aspects of schizophrenia without involving a gross anatomic lesion.

Age Factors↗