Estrogen receptor alpha containing neurons in the monkey forebrain: lack of association with calcium binding proteins and choline acetyltransferase.

The present study used single and dual immunohistochemistry to determine the topography and chemical phenotype of ERalpha containing neurons within the monkey forebrain utilizing antibodies directed against the full-length human ERalpha (NCL-ER-6F11), calcium-binding proteins calbindin-D(28k), and parvalbumin as well as choline acetyltransferase (ChAT). Our findings demonstrate for the first time ERalpha immunoreactive (-ir) cells in the monkey cerebral cortex (layers I-II) and in the claustrum. In addition, ERalpha-ir cells were seen in the septum, basal forebrain, amygdala and hypothalamus. Double-labeled cells for ERalpha and calbindin-D(28k) were seen only in the ventrolateral part of the ventromedial hypothalamic nucleus. In contrast, the co-localization of ERalpha and parvalbumin or ChAT was not seen in any of the areas of the monkey forebrain examined. These observations suggest that estrogens, at least in part, via ERalpha regulate calbindin-D(28k) hypothalamic but not parvalbumin or ChAT containing neurons in select monkey forebrain regions.

Analysis of gene expression in carbon tetrachloride-treated rat livers using a novel bioarray technology.

The present study successfully utilizes a new ADME Rat Expression Bioarray, containing 1040 metabolism- and toxicology-linked genes, to monitor gene expression from the livers of rats treated with carbon tetrachloride (CCl(4)). Histopathological analysis, hierarchical clustering methods, and gene expression profiling are compared between the control and CCl(4)-treated animals. A total of 44 transcripts were found to be altered in response to the hepatotoxin, 19 of which were upregulated and 25 were downregulated. Some of these gene expression changes were expected and concurred with previously published data while others were novel findings.

Reduction in TrkA-immunoreactive neurons is not associated with an overexpression of galaninergic fibers within the nucleus basalis in Down's syndrome.

Down's syndrome (DS) individuals develop neuropathological features similar to Alzheimer's disease (AD), including degeneration of cholinergic basal forebrain (CBF) neurons. In AD a reduction in CBF/trkA-containing neurons has been suggested to trigger a hyperexpression of galaninergic fibers within the nucleus basalis subfield of the basal forebrain. The present study examined the interrelationship between reductions in CBF/trkA-containing neurons and the overexpression of galaninergic fibers within the nucleus basalis in DS. Within the nucleus basalis stereologic evaluation revealed a 46% reduction in the number of trkA-immunopositive neurons, whereas optical density measurements displayed a nonsignificant 18% reduction in neuronal trkA immunoreactivity in DS as compared with age-matched controls. Western blot analysis also showed a significant reduction in cortical trkA protein levels in DS. A semiquantitative examination of galaninergic fibers in the nucleus basalis revealed only a modest hypertrophy of galaninergic fibers within the nucleus basalis in DS. The present findings indicate a significant reduction in trkA within the nucleus basalis and cortex with only a moderate hypertrophy of galaninergic fibers in DS. These observations suggest that DS may not be an exact genetic model for investigation of changes in the AD basal forebrain.

Distribution and retrograde transport of trophic factors in the central nervous system: functional implications for the treatment of neurodegenerative diseases.

Neurotrophins play a crucial role in the maintenance, survival and selective vulnerability of various neuronal populations within the normal and diseased brain. Several families of growth promoting substances have been identified within the central nervous system (CNS) including the superfamily of nerve growth factor related neurotrophin factors, glial derived neurotrophic factor (GDNF) and ciliary neurotrophic factor (CNTF). In addition, other non-neuronal growth factors such as fibroblast growth factor (FGF) have also been identified. This article reviews the trophic anatomy of these factors within the CNS. Intraventricular and intraparenchymal injections of exogenous nerve growth factor result in retrograde labeling mainly within the cholinergic basal forebrain. Distribution of brain derived neurotrophic factor (BDNF) following intraventricular injection is minimal due to the binding to the trkB receptor along the ventricular wall. In contrast, intraparenchymal injections of BDNF results in widespread retrograde transport throughout the CNS. BDNF has also been shown to be transported anterogradely within the CNS. Infusion of GDNF into the CNS results in retrograde transport limited to the nigrostriatal pathway. Hippocampal injections of NT-3 retrogradely label mainly basal forebrain neurons. Retrograde transport of radiolabeled CNTF has only been observed in sensory neurons of the sciatic nerve. Following intraventricular and intraparenchymal infusion of radiolabeled bFGF, retrograde neuronal labeling was found in the telecephalon, diencephalon, mesencephalon and pons. In contrast retrograde labeling for aFGF was found only in the hypothalamus and midbrain. Since select neurotrophins traffic anterogradely and retrogradely within the nervous system, these proteins could be used to treat neurological diseases such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis.

Morphometry of rat olfactory bulbs stained for cytochrome oxidase reveals that the entire population of glomeruli forms early in the neonatal period.

Cytochrome oxidase staining selectively highlights the synapse-rich neuropil of olfactory bulb glomeruli. Detailed morphometric enumeration of glomeruli in cytochrome oxidase-stained sections from postnatally developing rats reveals that the entire adult population of glomeruli (2400/bulb) forms early in life, the process being complete by days 3-5 postnatal. Newborn's glomeruli range in diameter from a mean of about 50 microns to a maximum of about 70 microns and undergo a 3-fold increase in diameter and a 20-fold increase in volume during days 1-50 postnatal. The presence of the entire adult's glomeruli in the neonate calls for a serious revision of some current views on glomerular development and, given the critical roles of glomeruli as modules, the findings bear important implications for the organization of olfactory system and early development of olfactory functions.

Paradoxical hypertrophy and plasticity of the testis in rats recovering from early thyroid deficiency: a growth study including effects of age and duration of hypothyroidism.

The effects of various durations of postnatal hypothyroidism followed by recovery were studied on testicular growth in Long-Evans and Sprague-Dawley rats from birth to 7 months. Hypothyroidism was induced by adding propylthiouracil (PTU) in drinking water (0.1%, w/v). Recovery was induced by withdrawal of PTU. Testicular growth was reduced in rat pups by 20, 65 and 90% at days 10, 25 and 50. Upon withdrawal of PTU at weaning (25 days), testicular growth resumed and became compensatory; catch-up growth occurred by day 65. Paradoxically, testicular growth progressively increased, surpassing the control weights by 40, 50 and 100% at days 75, 90 and 210. Maximal testicular growth rate in the recovery group was 35% higher, occurred 2 weeks later and lasted 2 weeks longer than controls. Testes of rats subjected to prolonged postnatal hypothyroidism (60 or 120 days) also showed recovery and hypertrophy, amounting to nearly twice the normal maximal growth levels, after at least 6 months of recovery. Body weights of recovering rats remained always significantly below those of controls. When the suckling pups were exposed to short, week-long regimes of PTU treatment, only rats treated during the early postnatal weeks (days 1-8 or 9-16) had enlarged testes; PTU treatment during the late suckling period (days 17-24) or later had no effects. Total duration of hypothyroidism in the suckling period was positively correlated with testicular enlargement. The results indicate that hypothyroidism early in life is stimulatory to testicular growth, resulting in a paradoxical twofold increase in final testicular size which occurs even if hypothyroidism is prolonged. These effects occur similarly in different strains of rat with differing sized testes. It is suggested that there is a sensitive period for this effect, i.e. during the first 2 weeks after birth. The marked plasticity of testicular growth as shown by its recovery and hypertrophy, even after long periods of hypothyroid retardation, is unique in the body and may be a useful model for studying hormonal factors regulating testicular growth and for animal breeding and research into infertility.