Microencephalic Rats as a Model for Cognitive Disorders

Balduini, Walter; Cimino, Mauro; Lombardelli, G.; Abbracchio, M.P.; Peruzzi, G.; Cecchini, Tiziana; Gazzanelli, Giancarlo; Cattabeni, F.

doi:10.1097/00002826-198406001-00379

Cited by 12 publications

(6 citation statements)

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“…Since microcephaly is one of the most evident postnatal features of MAM-treated animals (Balduini et al, 1986;Colacitti et al, 1999), we investigated differences in gross anatomical appearance and cortical thickness between MAM-treated and control animals at different developmental stages (Fig. 2).…”

Section: Mam-induced Pathophysiological Changesmentioning

confidence: 99%

Early cerebrovascular and parenchymal events following prenatal exposure to the putative neurotoxin methylazoxymethanol

Bassanini¹,

Hallene²,

Battaglia³

et al. 2007

Neurobiology of Disease

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One of the most common causes of neurological disabilities are malformations of cortical development (MCD). A useful animal model of MCD consists of prenatal exposure to methylazoxymethanol (MAM), resulting in a postnatal phenotype characterized by cytological aberrations reminiscent of human MCD. Although postnatal effects of MAM are likely a consequence of prenatal events, little is known on how the developing brain reacts to MAM. General assumption is the effects of prenatally administered MAM are short lived (24 h) and neuroblast-specific. MAM persisted for several days after exposure in utero in both maternal serum and fetal brain, but at levels lower than predicted by a neurotoxic action. MAM levels and time course were consistent with a different mechanism of indirect neuronal toxicity. The most prominent acute effects of MAM were cortical swelling associated with mild cortical disorganization and neurodegeneration occurring in absence of massive neuronal cell death. Delayed or aborted vasculogenesis was demonstrated by MAM's ability to hinder vessel formation. In vitro, MAM reduced synthesis and release of VEGF by endothelial cells. Decreased expression of VEGF, AQP1, and lectin-B was consistent with a vascular target in prenatal brain. The effects of MAM on cerebral blood vessels persisted postnatally, as indicated by capillary hypodensity in heterotopic areas of adult rat brain. In conclusion, these results show that MAM does not act only as a neurotoxin per se, but may additionally cause a short-lived toxic effect secondary to cerebrovascular dysfunction, possibly due to a direct anti-angiogenic effect of MAM itself.

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Section: Mam-induced Pathophysiological Changesmentioning

confidence: 99%

Early cerebrovascular and parenchymal events following prenatal exposure to the putative neurotoxin methylazoxymethanol

Bassanini¹,

Hallene²,

Battaglia³

et al. 2007

Neurobiology of Disease

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show abstract

“…nervous system [65,[68][69][70][71] because the toxin is proposed to selectively target DNA of neuroblasts during development [68,72,73] while sparing postmitotic neurons [68,74] and glial cells [75]. However, the detection of abnormal DNA (presumably alkylated guanine) in the brains of 1-year-old animals [67] treated earlier in life with MAM suggests that mature or postmitotic brain tissue is persistently damaged by the genotoxin.…”

Section: Mechanism Of Cycad-induced Neurodegenerationmentioning

confidence: 99%

Damage and Repair of Nerve Cell Dna in Toxic Stress*

Kisby

Kabel

Hugon

et al. 1999

Drug Metabolism Reviews

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“…Rodents with neuronal migration disorders exhibit various neurological deficits including ataxia in reeler mutant mice [23], learning disabilities in rats with prenatal MAM injection or irradiation [93][94][95] and seizure disorders or at least cortical hyperexcitability (reviewed in [96]). However, these animals also present other cerebral dysgenesis such as cerebellar atrophy in reeler mice or microcephaly in rats with prenatal MAM.…”

Section: Neurological Deficits In Rodents With Neuronal Migration Dismentioning

confidence: 99%

The right neuron at the wrong place: biology of heterotopic neurons in cortical neuronal migration disorders, with special reference to associated pathologies

Chevassus-au-Louis¹,

Represa²

1999

Cellular and Molecular Life Sciences (CMLS)

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During the development of the neocortex, neurogenesis and neuronal differentiation occur in two separate locations. Thus neurons have to migrate through the future white matter. Arrested or excessive migration leads neurons to differentiate in a heterotopic position. Such neuronal migration disorders (NMDs) occur sporadically in normal development but are markedly increased as a consequence of genetic defects or after exposure to toxic drugs during the period of migration. Anatomofunctional studies in rodents with NMDs have revealed that heterotopic neurons form essentially normal afferent and efferent connections, which has been interpreted as evidence that the connection pattern of cortical neurons is specified prior to migration. In addition, recent data show that heterotopic neurons can be contacted by environmental, that is local, fibres that normally never innervate the neocortex. This dual connectivity leads heterotopias to form bridges between their environmental and original network. Such an abnormal pattern of connectivity could contribute to the pathophysiology of disorders associated with NMDs such as epilepsy.

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Microencephalic Rats as a Model for Cognitive Disorders

Cited by 12 publications

References 0 publications

Early cerebrovascular and parenchymal events following prenatal exposure to the putative neurotoxin methylazoxymethanol

Early cerebrovascular and parenchymal events following prenatal exposure to the putative neurotoxin methylazoxymethanol

Damage and Repair of Nerve Cell Dna in Toxic Stress*

The right neuron at the wrong place: biology of heterotopic neurons in cortical neuronal migration disorders, with special reference to associated pathologies

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