Injury-induced neurogenesis in the mammalian forebrain

It has been accepted that new neurons are added to the olfactory bulb and the hippocampal dentate gyrus throughout life in the healthy adult mammalian brain. Recent studies have clarified that brain insult raises the proliferation of neural stem cells/neural progenitor cells existing in the subventricular zone and the subgranular zone, which become sources of new neurons for the olfactory bulb and the dentate gyrus, respectively. Interestingly, convincing data has shown that brain insult invokes neurogenesis in various brain regions, such as the hippocampal cornu ammonis region, striatum, and cortex. These reports suggest that neural stem cells/neural progenitor cells, which can be activated by brain injury, might be broadly located in the adult brain or that new neurons may migrate widely from the neurogenic regions. This review focuses on brain insult-induced neurogenesis in the mammalian forebrain, especially in the neocortex.     

The fate of choline in the circulating plasma of the rat

Summary Labelled free choline injected into the peritoneum failed to enter the brain but preferentially entered the liver. Subsequently labelled phospholipid was found in the plasma with a concurrent increase in the brain. This labelled plasma injected by cardiac puncture caused a rapid incorporation of the choline labelled phospholipid into the brain.     

The fate of choline in the circulating plasma of the rat.

Labelled free choline injected into the peritoneum failed to enter the brain but preferentially entered the liver. Subsequently labelled phospholipid was found in the plasma with a concurrent increase in the brain. This labelled plasma injected by cardiac puncture caused a rapid incorporation of the choline labelled phospholipid into the brain.     

Effect of diabetes on the enzymes of the cholinergic system of the rat brain

Choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activities were determined in several brain regions of normal and streptozotocin-induced diabetic rats. The diabetic rats exhibited significant increase in ChAT activity (p less than 0.05) in all brain regions studied except for the cortex and the midbrain. Meanwhile, the diabetes condition was associated with significant increase (p less than 0.05) in AChE activity of the bulbus olfactorius, medulla oblongata and cerebellum. These data suggest that uncontrolled diabetes is associated with significant alterations in the brain cholinergic systems.     

Morphology of the carnation-light synthetic lethal focus in Drosophila melanogaster

A histological study of the carnation-light lethal focus revealed morphological abnormalities in brain tissue. The ratio of core width to total brain width and brain texture consistently differed between lethal (car-lt) and their non-lethal sibs.     

Morphology of the carnation-light synthetic lethal focus inDrosophila melanogaster

Summary A histological study of the carnation-light lethal focus revealed morphological abnormalities in brain tissue. The ratio of core width to total brain width and brain texture consistently differed between lethal (car-lt) and their non-lethal sibs.     

Transketolase and 2-oxoglutarate dehydrogenase activities in the brain and liver of the developing rat

Rat brain transketolase showed little change in activity from birth to adulthood, whereas the liver enzyme activity increased in a biphasic way. In both brain and liver, 2-oxoglutarate dehydrogenase activity increased gradually after birth and reached a plateau at 5 weeks of age. A developmental change in thiamin content in the brain was similar to the change in the 2-oxoglutarate dehydrogenase activity, but this was not the case in the liver.     

Antiepileptic drugs and the developing brain

Epilepsy is the most common neurological disorder in young humans. Antiepileptic drugs (AEDs) which are used to treat seizures in infants, children and pregnant women can cause cognitive impairment, microcephaly and birth defects. Ion channels, neurotransmitters and second messenger systems constitute molecular targets of AEDs. The same targets regulate brain processes essential both for propagation of seizures and for learning, memory and emotional behavior. Thus, AEDs can influence brain function and brain development in undesired ways. Here we review mechanisms of action of AEDs, examine clinical evidence for their adverse effects in the developing human brain, and present studies on cognitive and behavioral effects in animal models. Furthermore, we discuss mechanisms responsible for adverse effects of AEDs in the developing mammalian brain, including interference with cell proliferation and migration, axonal arborization, synaptogenesis, synaptic plasticity and physiological apoptotic cell death. Received 3 August 2005; received after revision 13 October 2005; accepted 1 November 2005     

Pre- and postnatal lead exposure affects the serotonergic system in the immature rat brain

Summary The effect of pre- and postnatal lead exposure on the development of the serotonergic system in striatum and brain stem was investigated. Serotonin and its metabolite 5-HIAA where determined by HPLC-EC. A significant decrease of 5-HT was detected in the brain stem at postnatal day 28. At both days 6 and 28 postnatal, 5-HIAA was reduced in striatum and brain stem. The results provide support to the hypothesis that developing 5-HT neurons are sensitive to relatively low levels of lead exposure.     

Transketolase and 2-oxoglutarate dehydrogenase activities in the brain and liver of the developing rat

Summary Rat brain transketolase showed little change in activity from birth to adulthood, whereas the liver enzyme activity increased in a biphasic way. In both brain and liver, 2-oxoglutarate dehydrogenase activity increased gradually after birth and reached a plateau at 5 weeks of age. A developmental change in thiamin content in the brain was similar to the change in the 2-oxoglutarate dehydrogenase activity, but this was not the case in the liver.     

Aneuploidy in the normal and diseased brain

The brain is remarkable for its complex organization and functions, which have been historically assumed to arise from cells with identical genomes. However, recent studies have shown that the brain is in fact a complex genetic mosaic of aneuploid and euploid cells. The precise function of neural aneuploidy and mosaicism are currently being examined on multiple fronts that include contributions to cellular diversity, cellular signaling and diseases of the central nervous system (CNS). Constitutive aneuploidy in genetic diseases has proven roles in brain dysfunction, as observed in Down syndrome (trisomy 21) and mosaic variegated aneuploidy. The existence of aneuploid cells within normal individuals raises the possibility that these cells might have distinct functions in the normal and diseased brain, the latter contributing to sporadic CNS disorders including cancer. Here we review what is known about neural aneuploidy, and offer speculations on its role in diseases of the brain. Received 13 April 2006; received after revision 2 June 2006; accepted 13 July 2006     

Pre- and postnatal lead exposure affects the serotonergic system in the immature rat brain.

The effect of pre- and postnatal lead exposure on the development of the serotonergic system in striatum and brain stem was investigated. Serotonin and its metabolite 5-HIAA where determined by HPLC-EC. A significant decrease of 5-HT was detected in the brain stem at postnatal day 28. At both days 6 and 28 postnatal, 5-HIAA was reduced in striatum and brain stem. The results provide support to the hypothesis that developing 5-HT neurons are sensitive to relatively low levels of lead exposure.     

Delineating multiple functions of VEGF-A in the adult brain

Vascular endothelial growth factor-A (abbreviated throughout this review as VEGF) is mostly known for its angiogenic activity, for its activity as a vascular permeability factor, and for its vascular survival activity [1]. There is a growing body of evidence, however, that VEGF fulfills additional less ‘traditional’ functions in multiple organs, both during development, as well as homeostatic functions in fully developed organs. This review focuses on the multiple roles of VEGF in the adult brain and is less concerned with the roles played by VEGF during brain development, functions described elsewhere in this review series. Most functions of VEGF that are essential for proper brain development are, in fact, dispensable in the adult brain as was clearly demonstrated using a conditional brain-specific VEGF loss-of-function (LOF) approach. Thus, in contrast to VEGF LOF in the developing brain, a process which is detrimental for the growth and survival of blood vessels and leads to massive neuronal apoptosis [2–4], continued signaling by VEGF in the mature brain is no longer required for maintaining already established cerebral vasculature and its inhibition does not cause appreciable vessel regression, hypoxia or apoptosis [4–7]. Yet, VEGF continues to be expressed in the adult brain in a constitutive manner. Moreover, VEGF is expressed in the adult brain in a region-specific manner and in distinctive spatial patterns incompatible with an angiogenic role (see below), strongly suggesting angiogenesis-independent and possibly also perfusion-independent functions. Here we review current knowledge on some of these ‘non-traditional’, often unexpected homeostatic VEGF functions, including those unrelated to its effects on the brain vasculature. These effects could be mediated directly (on non-vascular cells expressing cognate VEGF receptors) or indirectly (via the endothelium). Experimental approaches aimed at distinguishing between these possibilities for each particular VEGF function will be described. This review is only concerned with homeostatic functions of VEGF in the normal, non-injured brain. The reader is referred elsewhere in this series for a review on VEGF actions in response to various forms of brain injury and/or brain pathology.     

The effect of proctolin on the adenylate and guanylate cyclases in the Locusta brain at various developmental stages.

Proctolin at concentrations 10(-8)-10(-7) M elevated by 40% brain adenylate cyclase activity of adult Locusta migratoria migratoriodes R.F. In moulting individuals, proctolin caused a decrease in brain adenylate cyclase activity, and it proved to be ineffective in the larvae. Proctolin caused only a slight decrease on guanylate cyclase activity of the brain at every developmental stage.     

Influence of corpora allata and brain extract on the lipid release from the fat body of termite queen Odontotermes assmuthi

Summary Short term in vitro experiments on the influence of the extracts of corpora allata and brain from the termite queenOdontotermes assmuthi on the lipid release from the fat body into the haemolymph indicated that the extract of corpora allata does not influence the lipid mobilization, whereas the brain extract increases the free fatty acid level in the haemolymph. It is believed that the brain extract stimulates triglyceride hydrolysis in the fat body.     

In vivo inactivation of transglutaminase during the acute acrylamide toxic syndrome in the rat

Summary The activity of liver and brain transglutaminase is rapidly lost following i.p. injection of acrylamide (50–200 mg/kg). Other enzymes investigated were not modified by the treatment, with the exception of brain enolase.     

Inter omental-cerebral vascularization induced by omental graft to the rat brain

Summary The omentum of 13 rats were removed from the abdomen and placed directly on the brain. 5–14 days later the omentum and the underlying brain were joined by numerous vascular anastomoses in 9 rats. The purpose of this work was to study the use of omentum to establish extracranial vascularization of the brain.Supported by funds from Grant RR 514 from the Jefferson Medical College General Research Fund.     

Cardioactive peptides of the CNS of the pulmonate snailLymnaea stagnalis

Summary In the pulmonate snailLymnaea stagnalis the cardioactive effects (tested on isolated auricles) of acetylcholine (ACh), 5-hydroxytryptamine (5-HT), the bivalve tetrapeptide FMRFamide, and of chromatographically separated snail brain substances have been established. Besides ACh and 5-HT, in brain extracts, small FMRFamide-like and large cardioexcitatory peptides were found.     

Effect of diabetes on the enzymes of the cholinergic system of the rat brain

Summary Choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activities were determined in several brain regions of normal and streptozotocin-induced diabetic rats. The diabetic rats exhibited significant increase in ChAT activity (p<0.05) in all brain regions studied except for the cortex and the midbrain. Meanwhile, the diabetes condition was associated with significant increase (p<0.05) in AChE activity of the bulbus olfactorius, medulla oblongata and cerebellum. These data suggest that uncontrolled diabetes is associated with significant alterations in the brain cholinergic systems.To whom requests of reprints should be addressed.This work was supported by grants from the National Aeronautics and Space Administration (NSG 2183 and NAG-2-411), a grant from the National Institutes of Health (NIH Grant RR0811) and a grant from the Division of Research Resources, National Institutes of Health (NIH Grant RR03020).     

Immunoreactive luteinizing hormone-containing neurons in the brain of the white-footed mouse, Peromyscus leucopus

The distribution of immunoreactive LH in the brain of the white-footed mouse (Peromyscus leucopus) was determined using immunocytochemical procedures. Immunoreactive fibers are located in the hypothalamus, preoptic area, septum and amygdala. Stained cell bodies are seen in the arcuate nucleus and preoptic area. Gonadectomy enhances staining for LH in the brain.