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Biomedical subjects

R F Mervis

Publications and source records attributed to R F Mervis.

16 recordsLinked to original sources
PubMed2000

Hippocampal abnormalities and enhanced excitability in a murine model of human lissencephaly.

Human cortical heterotopia and neuronal migration disorders result in epilepsy; however, the precise mechanisms remain elusive. Here we demonstrate severe neuronal dysplasia and heterotopia throughout the granule cell and pyramidal cell layers of mice containing a heterozygous deletion of Lis1, a mouse model of human 17p13.3-linked lissencephaly. Birth-dating analysis using bromodeoxyuridine revealed that neurons in Lis1+/- murine hippocampus are born at the appropriate time but fail in migration to form a defined cell layer. Heterotopic pyramidal neurons in Lis1+/- mice were stunted and possessed fewer dendritic branches, whereas dentate granule cells were hypertrophic and formed spiny basilar dendrites from which the principal axon emerged. Both somatostatin- and parvalbumin-containing inhibitory neurons were heterotopic and displaced into both stratum radiatum and stratum lacunosum-moleculare. Mechanisms of synaptic transmission were severely disrupted, revealing hyperexcitability at Schaffer collateral-CA1 synapses and depression of mossy fiber-CA3 transmission. In addition, the dynamic range of frequency-dependent facilitation of Lis1+/- mossy fiber transmission was less than that of wild type. Consequently, Lis1+/- hippocampi are prone to interictal electrographic seizure activity in an elevated [K(+)](o) model of epilepsy. In Lis1+/- hippocampus, intense interictal bursting was observed on elevation of extracellular potassium to 6.5 mM, a condition that resulted in only minimal bursting in wild type. These anatomical and physiological hippocampal defects may provide a neuronal basis for seizures associated with lissencephaly.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1998

Dendritic alterations in cortical pyramidal cells in the sparse fur mouse.

Ornithine carbamoyltransferase deficiency, an X-linked trait, leads to toxic hyperammonemia in sparse fur (spf/Y) mice. Quantitative analysis of the basilar dendritic tree of layer V pyramidal cells in frontoparietal cortex stained by the Golgi Kopsch method revealed a significant decrease in both the complexity of the dendritic arbor and in dendritic terminal spine density (60%) in spf/Y mice compared with controls. Such reductions may contribute to behavioral dysfunction observed in spf/Y mice.

Animals↗
PubMed1994

gp120 as an etiologic agent for NeuroAIDS: neurotoxicity and model systems.

The search for an agent that can mediate the symptoms of NeuroAIDS has been directed at gp120, the major envelope protein from HIV. The toxicity associated with gp120 was examined as a model and predictor of the neuropathological and neuropsychiatric manifestations of AIDS. Studies of the neurotoxic effects of purified gp120 on neurons from the rodent CNS cell cultures indicated the following: potent and selective killing of subpopulations of hippocampal neurons; varying potency of gp120s obtained from various HIV isolates; complete and potent protection from gp120 killing action after treatment with peptides related to vasoactive intestinal peptide; and obligatory presence of glia for gp120-related toxicity. Investigations of gp120 treatment of rodents revealed: cortical neurodystrophy with reduced arborizations and swollen processes; delays in developmental behaviors involving motor skills; peptide T prevention or attenuation of the morphological and behavioral deficits/delays produced by administration of gp120; and impairment of learning in the Morris swim maze. In addition, studies of subcutaneously administered, radiolabeled gp120 in neonatal animals demonstrated the presence of toxic fragments of gp120 in the developing brain. With the use of model test systems of non-human derived cell cultures and neonatal rats, we have captured and predicted a number of the morphological and behavioral deficits associated with AIDS. These multi-disciplinary studies of the actions of gp120 and associated fragments in rodents and rodent cells predict that the loss of cognitive and neurological function in patients with AIDS are attributed in part to interference of critical brain functions by the envelope protein, gp120.

AIDS Dementia Complex↗
PubMed1993

HIV envelope protein-induced neuronal damage and retardation of behavioral development in rat neonates.

Cognitive and motor impairment are common symptoms among patients infected with the human immunodeficiency virus (HIV), including children who suffer neurological deficits and are frequently developmentally impaired. The HIV envelope protein, gp120, which has been shown to be toxic to neurons in culture, is shed in abundance by infected cells, and thus may play a significant role in the neuropathology of AIDS. To test this possible mechanism, neonatal rats were injected systemically with purified gp120 and the following consequences were observed: (1) radiolabeled gp120 and toxic fragments thereof were recovered in brain homogenates; (2) dystrophic changes were produced in pyramidal neurons of cerebral cortex; (3) retardation was evident in developmental milestones associated with complex motor behaviors. In parallel studies, co-treatment with peptide T, a gp120-derived peptide having a pentapeptide sequence homologous with vasoactive intestinal peptide, prevented or attenuated the morphological damage and behavioral delays associated with gp120 treatment. These studies suggest that gp120 and gp120-derived toxic fragments may contribute to the neurological and neuropsychiatric impairment related to HIV infection, and that peptide T appears to be effective in preventing gp120-associated neurotoxicity in developing rodents.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Exogenous nerve growth factor reverses age-related structural changes in neocortical neurons in the aging rat. A quantitative Golgi study.

The role of chronic exogenous intracerebroventricular administration of nerve growth factor (NGF) on the morphology of layer V pyramidal cell dendrites in aging rats was quantified using Golgi impregnations. Both dendritic branching and dendritic spines from the basilar tree of randomly selected pyramidal neurons of the frontal cortex were evaluated in young control (4-month-old) Fischer 344 rats, in old controls (24-month-old), and in 24-month-old rats administered NGF for 4 weeks. Sholl analysis of basilar dendritic trees showed that neuronal branching in older rats was significantly greater than that in young rats (probably due to compensatory dendritic hypertrophy). The extent of dendritic material in aged rats receiving NGF, however, was identical to that in young rats, that is, the dendritic tree had regressed in size. Dendritic spine response to NGF treatment depended on the region of the dendritic tree sampled. Normal aging resulted in spine loss. However, NGF treatment restored dendritic spine densities to those seen in young controls on terminal tip segments ("plastic" regions). Internal branch segments ("nonplastic" regions) showed no response to NGF. As dendritic spines are thought to represent the neuroanatomic basis of learning and memory, results suggest that NGF can influence the morphology of cortical neurons (probably indirectly via the basal forebrain projections) and therefore may play an efficacious role in the treatment of geriatric cognitive dysfunction and even perhaps in Alzheimer's disease.

Aging↗
PubMed1989

The effects of rHuIFN-alpha A/D on brain lipids and behavior of neonatal ICR Swiss albino mice.

Systemic administration of interferon (IFN) can cause reversible neurologic side effects, but there is little information on its effect on the developing nervous system. We studied the effects of daily, subcutaneous injections of recombinant human interferon-alpha A/D (rHuIFN-alpha A/D) (which has biological activity in mice) on brain development of neonatal ICR Swiss albino mice. Animals were treated daily between 8 and 20 days of age (doa) with 5 x 10(4) units (U) of rHuIFN-alpha A/D and sacrificed at 24, 62, and 111 doa following testing in an active avoidance paradigm. Results show that rHuIFN-alpha A/D causes transient decreases in body and brain weights. There were no changes in brain total lipid, ganglioside, phosphorus, or cholesterol content, but there was a transient decrease in neutral glycolipid content. In addition, treated animals exhibited decreased spontaneous activity levels and an impaired retention of a learned behavior. These results suggest that there are some long-term treatment effects on behavior following administration of rHuIFN-alpha A/D to mice during the neonatal period.

Animals↗
PubMed1985

Dietary choline affects response to acetylcholine by isolated urinary bladder.

Age-related increases occur in the response of isolated urinary bladders to the parasympathetic neurotransmitter acetylcholine (ACh). Experiments were carried out to determine whether long-term elevation or diminution in the amount of ingested choline can also affect the response of the urinary bladder to ACh. Female C57BL/6J mice were maintained on a choline-deficient chow and on drinking water supplemented with either 0, 1.5, or 4.0 mg/ml choline chloride from 8 to 20 months of age. Isolated bladders from choline deficient animals showed a 46% increase in the maximum response to ACh as compared to those from normal choline animals, while bladders from animals on choline enriched diets showed a 15% decrease in maximum contractile response. Radioligand binding experiments suggested that the functional changes result from alterations in the density of muscarinic receptors in the bladder. The results are consistent with the hypothesis that muscarinic receptors are down-regulated to compensate for increased parasympathetic activity associated with choline-enriched diets and up-regulated to compensate for decreased parasympathetic activity associated with choline-deficient diets.

Acetylcholine↗
PubMed1985

Chronic dietary choline modulates synaptic plasticity in the cerebellar glomeruli of aging mice.

A morphometric investigation was carried out on ethanolic phosphotungstic acid (E-PTA) stained synaptic junctions in the cerebellar glomeruli of adult, old, old choline-deficient and old choline-supplemented mice. Numerical (Nv) and surface (Sv) density as well as average length (L) of the synapses were calculated on 100 pictures per group. A significant reduction of Nv and Sv, as well as an increase of L was found during aging. Choline deficient animals did not show any change as compared to old animals of the same age. In choline supplemented mice Nv and Sv were significantly increased and L significantly decreased, respectively, as compared to old control littermates. No difference was found between adult and choline supplemented mice. In the cerebellar glomeruli only a small fraction of fibers are cholinergic, therefore the present findings support the idea that dietary choline can influence systems other than cholinergic. The possible role of choline supplementation in the modulation of synaptic plasticity via the synthesis and/or turnover of neuronal membrane choline phospholipids, is discussed.

Animals↗
PubMed1984

Development and maturation of postural reflexes in normal kittens.

In order to evaluate neurologic development, postural reflexes were tested in normal kittens from birth through 7 weeks of age until stable adult patterns of performance were attained. These reflex tests included: body and air righting, visual placing, chin placing, tactile placing, hopping, and locomotion. A protocol for scoring responses was designed for each individual reflex to differentiate their progression. The first reflexes to mature were visual placing, chin placing, and body righting which attained a maximal score during the 3rd week of life. This was followed by maturation of the forelimb hopping reflex and independent locomotion during the 4th week. Forelimb tactile placing responses, hind limb hopping reflexes, and air righting developed by the 5th week. Hind limb tactile placing responses were the last to mature. They became fully expressed in the 6th week. The pattern of ontogeny of these reflexes proceeded in a cephalocaudal direction. This is in agreement with earlier observations of others who correlated the maturation of reflex responses in kittens with myelination in the central nervous system.

Aging↗
PubMed1976

The split-brain neonate: a surgical method for corpus callosum section in newborn kittens.

One way to determine the importance of interhemispheric interaction in the development of adaptive and acquired behavior is to section completely the corpus callosum about the time of birth before myelination commences and before any significant hemispheric interaction takes place. Therefore, we developed a technique for commissurotomy in the neonatal kitten 36 to 72 hr of age. A specially designed "commissurotomy knife" was used which eliminated retraction of the hemispheres. Histology showed completeness of corpus callosum section as well as commissure of the fornix without any apparent damage to cortical or subcortical structures. This technique meets the following criteria: (1) reproducibility or lesions without additional nonspecific damage; (2)minimal exposure and manipulation of the delicate newborn brain: (3) brief operational procedure minimizing risk of infection; and (4) low mortality rate.

Anesthetics↗
PubMedDate not supplied

Dietary restriction suppresses age-related changes in dendritic spines.

The effects of dietary restriction by every-other-day (EOD) feeding on dendritic spines in the aging rat neocortex were evaluated in Golgi preparations. After weaning, male Wistar rats were offered a 24% protein diet either ad lib (AL) or EOD. AL-fed groups were sacrificed at 6 and 24-25 months of age. EOD-fed groups were sacrificed at 6, 24, and 30 months. To assess the effects of EOD feeding late in life, another group was fed AL for 19 months, then EOD for 5 months and sacrificed when 24 months old. Spine density and configuration were quantified along 20 microns terminal tip segments from the basilar tree of layer V pyramidal cells of the parietal cortex. Evaluation of spine densities from the 6 and 24 months AL-fed groups showed that there was a significant loss of spines with normal aging (-38%). In EOD-fed rats, spine density did not differ significantly from AL age-matched controls at either 6 or 24 months of age. However, spine densities in 24-month-old rats diet restricted late in life and EOD-fed 30-month-old rats were the same as 6-month-old AL-fed controls and EOD 6-month-old rats, an observation suggesting protection of dendritic spines from age-related loss. Spines were categorized as either L-type (lollipop-shaped), which are more prevalent in young adults, or N-type (nubbin). With normal aging (comparing 6- and 24-month-old AL-fed groups) there was a significant decrease in L-type spines. However, all dietarily restricted groups showed retention of L-type spines.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMedDate not supplied

Nimodipine facilitates retention of the classically conditioned nictitating membrane response in aged rabbits over long retention intervals.

Aged rabbits initially underwent 18 days of acquisition of the classically conditioned nictitating membrane response (NMR) using a tone conditioned stimulus (CS) and an air puff unconditioned stimulus (UCS). They were then treated with a low or high dose of nimodipine or a vehicle for 90 days. During this time no further CS-UCS pairings were presented. They underwent testing for retention of the conditioned response (CR) at 30 and 90 days. Retention testing consisted of 20 presentations of the CS alone. Rabbits in the control condition retained 46.4% of their predrug levels of conditioned responding and rabbits receiving the low dose of nimodipine retained 37.3% of their predrug levels after 30 days. After 90 days, retention in these animals declined to 8.1% and 14.1%, respectively. In contrast, rabbits receiving the high dose of nimodipine retained 85% of their predrug learning at 30 days with little decline at 90 days (77.1%). Nonassociative factors such as sensitivity to the CS or UCS could not explain these effects.

Aging↗
PubMedDate not supplied

Oral and subcutaneous administration of the glycosaminoglycan C3 attenuates Abeta(25-35)-induced abnormal tau protein immunoreactivity in rat brain.

High molecular weight glycosaminoglycans (GAG) and proteoglycans (PG) affect pathological changes of the brain in Alzheimer's disease (AD). PG stimulate the processing and aggregation of amyloid-beta (Abeta), protect the protein from proteolysis, and increase the formation of neurofibrillary tangles by inducing the hyperphosphorylation of tau protein. These effects may be competitively inhibited by GAG. We have studied the effects of orally (by gavage) and subcutaneously (s.c.) administered low molecular weight heparin, C3 (4-10 oligosaccharides; MW = 2.1 kDa; USP value = 12 U/mg), on abnormal tau-2 protein immunoreactivity in the rat hippocampus following a single, unilateral intra-amygdaloid administration of Abeta(25-35). Oral administration of C3 (25 mg/kg; once daily) was initiated 3 days prior to Abeta(25-35) administration, and was continued daily for an additional 14 days. S.c. administration of C3 (2.5 mg/kg, twice daily), was started 3 days prior to, and was continued for 32 days after, Abeta(25-35) administration. Animal brains were subsequently processed for tau-2, ChAT-immunoreactivity, choline acetyltransferase (ChAT) activity and acetylcholinesterase (AChE) activity. Both oral and s.c. administration of C3 attenuated Abeta(25-35) induced appearance of tau-2-immunoreactive (IR) perikarya in the ipsilateral hippocampus (P < 0.05). Hippocampal cholinergic enzyme activity in C3 treated animals was not significantly different from control animals. The present findings suggest that C3 might be used successfully to prevent abnormal tau protein formation in chronic neurologic diseases, such as AD. Moreover, our data demonstrate that the mechanism of this effect does not appear to influence the cholinergic system of the brain.

Acetylcholinesterase↗