Adult subventricular zone neuronal precursors continue to proliferate and migrate in the absence of the olfactory bulb.
Neurons continue to be born in the subventricular zone (SVZ) of the lateral ventricles of adult mice. These cells migrate as a network of chains through the SVZ and the rostral migratory stream (RMS) into the olfactory bulb (OB), where they differentiate into mature neurons. The OB is the only known target for these neuronal precursors. Here, we show that, after elimination of the OB, the SVZ and RMS persist and become dramatically larger. The proportion of dividing [bromodeoxyuridine (BrdU)-labeled] or dying (pyknotic or terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end-labeled) cells in the RMS was not significantly affected at 3 d or 3 weeks after bulbectomy (OBX). However, by 3 months after OBX, the percentage of BrdU-labeled cells in the RMS decreased by half and that of dying cells doubled. Surprisingly, the rostral migration of precursors continued along the RMS after OBX. This was demonstrated by focal microinjections of BrdU and grafts of SVZ cells carrying LacZ under the control of a neuron-specific promoter gene. Results indicate that the OB is not essential for proliferation and the directional migration of SVZ precursors. (+info
Effect of individual or combined ablation of the nuclear groups of the lamina terminalis on water drinking in sheep.
The subfornical organ (SFO), organum vasculosum of the lamina terminalis (OVLT), and median preoptic nucleus (MnPO) were ablated either individually or in various combinations, and the effects on drinking induced by either intravenous infusion of hypertonic 4 M NaCl (1.3 ml/min for 30 min) or water deprivation for 48 h were studied. Ablation of either the OVLT or SFO alone did not affect drinking in response to intravenous 4 M NaCl, although combined ablation of these two circumventricular organs substantially reduced but did not abolish such drinking. Ablation of the MnPO or MnPO and SFO together also substantially reduced, but did not abolish, drinking in response to intravenous hypertonic NaCl. Only near-total destruction of the lamina terminalis (OVLT, MnPO, and part or all of the SFO) abolished acute osmotically induced drinking. The large lesions also reduced drinking after water deprivation, whereas none of the other lesions significantly affected such drinking. None of these lesions altered feeding. The results show that all parts of the lamina terminalis play a role in the drinking induced by acute increases in plasma tonicity. The lamina terminalis appears to play a less crucial role in the drinking response after water deprivation than for the drinking response to acute intravenous infusion of hypertonic saline. (+info
Volumetric change of the lateral ventricles in the human brain following glucose loading.
Lateral ventricular volumes were monitored and quantified using accurately registered magnetic resonance images (MRIs) in six healthy individuals 30 min before and up to 4 h after ingestion of a glucose drink. The volume of the lateral ventricles increased by an average (+/- S.E.M.) of 2.4 +/- 0.4% as blood glucose levels rose from 4.8 +/- 0.2 mmol l-1 to 8.4 +/- 0.4 mmol l-1. This was followed by a peak decrease of 5.99 +/- 3.3% below initial fasting volumes as blood glucose levels fell to 5.0 +/- 0.3 mmol l-1. We suggest that the secondary volume decrease demonstrates a homeostatic process of brain volume regulation for which the mechanism remains uncertain. (+info
Hyaline membrane disease, alkali, and intraventricular haemorrhage.
The relation between intraventricular haemorrhage (IVH) and hyaline membrane disease (HMD) was studied in singletons that came to necropsy at Hammersmith Hospital over the years 1966-73. The incidence of IVH in singleton live births was 3-22/1000 and of HMD 4-44/1000. Although the high figures were partily due to the large number of low birthweight infants born at this hospital, the incidence of IVH in babies weighing 1001-1500 g was three times as great as that reported in the 1658 British Perinatal Mortality Survey. Most IVH deaths were in babies with HMD, but the higher frequency of IVH was not associated with any prolongation of survival time of babies who died with HMD as compared with the 1958 survey. IVH was seen frequently at gestations of up to 36 weeks in babies with HMD but was rare above 30 weeks' gestation in babies without HMD. This indicated that factors associated with HMD must cause most cases of IVH seen at gestations above 30 weeks. Comparison of clinical details in infants with HMD who died with or without IVH (at gestations of 30-37 weeks) showed no significant differences between the groups other than a high incidence of fits and greater use of alkali therapy in the babies with IVH. During the 12 hours when most alkali therapy was given, babies dying with IVD received a mean total alkali dosage of 10-21 mmol/kg and those dying without IVH 6-34 mmol/kg (P less than 0-001). There was no difference in severity of hypoxia or of metabolic acidosis between the 2 groups. Babies who died with HMD and germinal layer haemorrhage (GLH) without IVH had received significantly more alkali than those who died with HMD alone, whereas survivors of severe respiratory distress syndrome had received lower alkali doses than other groups. It is suggested that the greatly increased death rate from IVH in babies with HMD indicates some alteration of management of HMD (since 1958) as a causative factor. Liberal use of hypertonic alkali solutions is the common factor which distinguishes babies dying with GLH and IVH from other groups of babies with HMD. Although the causal nature of this association remains unproved, it seems justifiable to lrge caution in alkali usage. (+info
Apparent loss and hypertrophy of interneurons in a mouse model of neuronal ceroid lipofuscinosis: evidence for partial response to insulin-like growth factor-1 treatment.
The neuronal ceroid lipofuscinoses (NCL) are progressive neurodegenerative disorders with onset from infancy to adulthood that are manifested by blindness, seizures, and dementia. In NCL, lysosomes accumulate autofluorescent proteolipid in the brain and other tissues. The mnd/mnd mutant mouse was first characterized as exhibiting adult-onset upper and lower motor neuron degeneration, but closer examination revealed early, widespread pathology similar to that seen in NCL. We used the autofluorescent properties of accumulated storage material to map which CNS neuronal populations in the mnd/mnd mouse show NCL-like pathological changes. Pronounced, early accumulation of autofluorescent lipopigment was found in subpopulations of GABAergic neurons, including interneurons in the cortex and hippocampus. Staining for phenotypic markers normally present in these neurons revealed progressive loss of staining in the cortex and hippocampus of mnd/mnd mice, with pronounced hypertrophy of remaining detectable interneurons. In contrast, even in aged mutant mice, many hippocampal interneurons retained staining for glutamic acid decarboxylase. Treatment with insulin-like growth factor-1 partially restored interneuronal number and reduced hypertrophy in some subregions. These results provide the first evidence for the involvement of interneurons in a mouse model of NCL. Moreover, our findings suggest that at least some populations of these neurons persist in a growth factor-responsive state. (+info
A quantitative MR study of the hippocampal formation, the amygdala, and the temporal horn of the lateral ventricle in healthy subjects 40 to 90 years of age.
BACKGROUND AND PURPOSE: Several investigators have defined normal age-specific values for the medial temporal lobe structures in neurologically normal elderly subjects, but, to our knowledge, no one has reported those values for a large sample of healthy volunteers. The purpose of our study was to define normal age-specific values for the hippocampal formation, the amygdala, and the temporal horn of the lateral ventricle by age group, ranging from 40 to 90 years, in order to generate a guideline for the quantitative MR diagnosis and differential diagnosis for early Alzheimer disease. METHODS: MR-based volumetric measurements of the hippocampal formation, the amygdala, and the temporal horn, standardized by total intracranial volume, were obtained from oblique coronal and sagittal T1-weighted MR images in 619 healthy volunteers and two cadaveric specimens. RESULTS: Differences in standardized volumes of the hippocampal formation, the amygdala, and the temporal horn were significant among the 61- to 70-year-old, 71- to 80-year-old, and 81- to 90-year-old groups, and were not significant between the 40- to 50-year-old and 51- to 60-year-old groups. We found no significant differences in side or sex among the age groups for any of the structures. CONCLUSION: Differences in the mean value and in the 95% normal range of standardized volumes of the hippocampal formation, the amygdala, and the temporal horn correspond to differences in age among healthy subjects; therefore, age should be considered a factor in correlative research, especially in that involving patients in the early stages of Alzheimer disease. (+info
Blood pressure reduction and diabetes insipidus in transgenic rats deficient in brain angiotensinogen.
Angiotensin produced systemically or locally in tissues such as the brain plays an important role in the regulation of blood pressure and in the development of hypertension. We have established transgenic rats [TGR(ASrAOGEN)] expressing an antisense RNA against angiotensinogen mRNA specifically in the brain. In these animals, the brain angiotensinogen level is reduced by more than 90% and the drinking response to intracerebroventricular renin infusions is decreased markedly compared with control rats. Blood pressure of transgenic rats is lowered by 8 mmHg (1 mmHg = 133 Pa) compared with control rats. Crossbreeding of TGR(ASrAOGEN) with a hypertensive transgenic rat strain exhibiting elevated angiotensin II levels in tissues results in a marked attenuation of the hypertensive phenotype. Moreover, TGR(ASrAOGEN) exhibit a diabetes insipidus-like syndrome producing an increased amount of urine with decreased osmolarity. The observed reduction in plasma vasopressin by 35% may mediate these phenotypes of TGR(ASrAOGEN). This new animal model presenting long-term and tissue-specific down-regulation of angiotensinogen corroborates the functional significance of local angiotensin production in the brain for the central regulation of blood pressure and for the pathogenesis of hypertension. (+info
Recovery from anterograde and retrograde amnesia after percutaneous drainage of a cystic craniopharyngioma.
A case is reported of a cystic craniopharyngioma involving the floor and walls of the third ventricle. Pronounced anterograde and retrograde amnesia were documented preoperatively by formal testing. Rapid improvement in both new learning capacity and remote memory occurred after percutaneous twist drill drainage of the cystic portion of the tumour. The relevance of these observations to the amnesic syndrome and its neuropathological basis is discussed. (+info