Combined toxicity of prenatal bacterial endotoxin exposure and postnatal 6-hydroxydopamine in the adult rat midbrain

Ling, Zaodung; Chang, Qing; Lipton, Jack W.; Tong, Chong Wai; Landers, Teresa M.; Carvey, Paul M.

doi:10.1016/j.neuroscience.2003.12.017

Cited by 111 publications

(82 citation statements)

References 60 publications

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“…Our values of 73967184 (males) and 66377243 (females) closely approximate the average of the published estimates and confirm a maledominant sex difference. There are fewer publications on VTA cell numbers, and, although our data for males (5167 + 118) and females (6202 + 121) fall below other estimates in rats of 10,200 (German and Manaye, 1993) and 18 723 (Ling et al, 2004), they are of a similar magnitude to those for the SNc, which is in agreement with other studies in the rat (German and Manaye, 1993) and the mouse (Blum, 1998). In addition, we believe that our data are the first to show that there is a significant sex difference in DA neuron numbers in the VTA but, unlike the SNc, values are greater in females than males.…”

Section: Midbrain Da Population Sizecontrasting

confidence: 85%

The Size and Distribution of Midbrain Dopaminergic Populations are Permanently Altered by Perinatal Glucocorticoid Exposure in a Sex- Region- and Time-Specific Manner

McArthur

McHale

Gillies

2006

Neuropsychopharmacol

110

106

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Central dopaminergic (DA) systems appear to be particularly vulnerable to disruption by exposure to stressors in early life, but the underlying mechanisms are poorly understood. As endogenous glucocorticoids (GCs) are implicated in other aspects of neurobiological programming, this study aimed to characterize the effects of perinatal GC exposure on the cytoarchitecture of DA populations in the substantia nigra pars compacta (SNc) and the ventral tegmental area (VTA). Dexamethasone was administered non-invasively to rat pups via the mothers' drinking water during embryonic days 16-19 or postnatal days 1-7, with a total oral intake circa 0.075 or 0.15 mg/ kg/day, respectively; controls received normal drinking water. Analysis of tyrosine hydroxylase-immunoreactive cell counts and regional volumes in adult offspring identified notable sex differences in the shape and volume of the SNc and VTA, as well as the topographical organization and size of the DA populations. Perinatal GC treatments increased the DA population size and altered the shape of the SNc and VTA as well as the organization of the DA neurons by expanding and/or shifting them in a caudal direction. This response was sexually dimorphic and included a feminization or demasculinization of the three-dimensional cytoarchitecture in males, and subtle differences that were dependent on the window of exposure. These findings demonstrate that inappropriate perinatal exposure to GCs have enduring effects on the organization of midbrain DA systems that are critically important for normal brain function throughout life.

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Section: Midbrain Da Population Sizecontrasting

confidence: 85%

The Size and Distribution of Midbrain Dopaminergic Populations are Permanently Altered by Perinatal Glucocorticoid Exposure in a Sex- Region- and Time-Specific Manner

McArthur

McHale

Gillies

2006

Neuropsychopharmacol

110

106

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“…The brains were dissected while still frozen as previously described (Ling et al, 2004). The striatum, midbrain, frontal cortex and cerebellum were isolated and weighted.…”

Section: Preparation Of Brain Homogenatesmentioning

confidence: 99%

Age-related changes in glutathione and glutathione-related enzymes in rat brain

2006

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The most reliable and robust risk factor for some neurodegenerative diseases is aging. It has been proposed that processes of aging are associated with the generation of reactive oxygen species and a disturbance of glutathione homeostasis in the brain. Yet, aged animals have rarely been used to model the diseases that are considered to be age-related such as Parkinson's or Alzheimer's disease. This suggests that the results from these studies would be more valuable if aged animals were used. The present study was designed to provide insight into the glutathione redox state in young and aged rat siblings of both genders by studying the enzyme activities related to glutathione synthesis, cycling, and usage. The results suggested a significant age-related reduction of reduced glutathione (GSH) level in all brain regions examined, associated with an increase of GSH oxidation to glutathione disulfide (GSSG) and decrease of the GSH/GSSG ratio. These changes were accompanied by diminished γ-glutamylcysteine synthetase activity in de novo glutathione synthesis and increased lipid peroxidation. In addition, these changes were associated with increased enzyme activities related to the GSH usage (glutathione peroxidase, γ-glutamyl transpeptidase, and glutathione Stransferase). The results indicate that aged animals are likely more vulnerable to oxidative stress and insinuate the roles of aged animals in modeling age-related neurodegeneration diseases.

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“…This model was subsequently investigated but with prenatally LPS-exposed rats treated with rotenone rather than 6-OHDA postnatally. The combined effects of LPS and rotenone produced a synergistic TH + cell loss in the SN relative to controls, which was associated with increased striatal-dopamine activity, TNF and increased reactive microglia (Ling et al, 2004).…”

Section: Systemic Inflammation and Parkinson's Diseasementioning

confidence: 95%