Changes in dendrites of cortical neurons in experimental alcohol intoxication

Dendrites of cortical neurons were studied in rats in the different stages of alcohol intoxication. Two categories of changes in the dendrites develop under these circumstances: destructive and compensatory. The dynamics of these changes depends on the periods of alcohol intoxication and individual differences in the central nervous system of the animals.Brain Institute, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR N. K. Bogolepov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 85, No. 1, pp. 87–89, January, 1978.     

Alterations of cortical neurons and their dendrites after chronic alcohol intoxication

Alterations occurring in the neurons of rat sensorimotor cortex 1, 2, and 4 months after a 4-month alcohol intoxication and 1 and 4 months after a 1-year alcoholization are studied by the methods of Nissl and Golgi. Pronounced dystrophic changes in cortical neurons and dendrites as well as reparative processes in the cell body are revealed 1 month after a 4-month intoxication. The recovery period for the upper cortical layer neurons (phylogenetically younger) is faster than that of neurons from the lower layers (phylogenetically older), as well as that of hypochromatousvs. hyperchromatous cells. Normalization of dendrite structure is slower than that of the cell body. Four months after a 1-year alcohol intoxication the structure of cortical neurons and dendrites is not restored. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 122, No. 10, pp. 467–470, October, 1996     

Responses of cortical neurons to microiontophoretic application of acetylcholine to their dendrites

Spike responses of neurons to the microiontophoretic application of acetylcholine to the soma and the dendrites were studied. The somatic and dendritic membranes had virtually equal sensitivity to acetylcholine. Only activatory responses were seen, which were most typical of spontaneously active neurons. Muscarinic activation induced spike responses with equal latent periods and equal intensities on application of acetylcholine to dendrites and the soma. It is suggested that intracellular chemical signaling is involved in the propagation of cholinergic excitation via dendrites. Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow. Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino. Translated from Zhurnal Vysshei Nervnoi Deyatel'nosti, Vol. 46, No. 5, pp. 893–903, September–October, 1996.     

The growth of dendrites in the mammalian brain

Summary The histological features of developing dendrites are analyzed in age-graded series of cats, rats, rabbits, and opossums with the Golgi techniques. Growth cones and filopodia are consistent features of growing dendrites in the sensory nuclei, motor cranial nerve nuclei, brain stem reticular formation, cerebellar cortex, midbrain tectum, thalamus, hypothalamus, striatum, olfactory bulb, hippocampus, pyriform lobe, and neopallium. Terminal dendritic growth cones occur at the tips of dendrites; preterminal growth buds occur on the dendritic shafts. Filopodia are conspicuous on the growth cones and buds, but they occur on the dendritic shafts, also. Terminal growth cones, preterminal growth buds, and filopodia associate with incipient dendritic branches. Growth cones and filopodia generally disappear when the neurons are completely differentiated. But some dendritic growth cones persist after the rest of the brain is mature and consequently may be involved in learning and other plastic changes in neural function. The analysis illustrates the following general trends in neural ontogeny, none of which are expressed without modifications and qualifications. The dendrites of the specific types of neurons differentiate in typically circumscribed periods, which occur in a fixed sequence. Within, a specific neuronal population there may be regional gradients in the degree of dendritic differentiation. Within the same region the dendrites of large cell bodies tend to differentiate before those of small cell, bodies. The dendrites of Golgi Type II neurons differentiate later than neurons with long axons from the same thalamic nucleus. In the afferent sensory systems the neurons nearer the peripheral receptors usually begin their differentiation before those nearer the cerebral cortex. The dendrites of phylogenetically older neuronal groups tend to differentiate earlier than those of more advanced or more highly specialized groups. The dendrites and the other post-synaptic surfaces of the neurons differentiate in conjunction with the particular afferent axonal end-branches that are destined to synapse with the dendrites. Dendritic differentiation may be instigated by the afferent axons, controlled by local physico-chemical conditions, and guided by contact with the afferent axonal end-branches.Supported in part by U. S. Public Health Service Research Grant NB 06115.With the technical aid of Mrs. R.R. Morest and of Miss P.E. Palmer. The author gratefully acknowledges the encouragement of Prof. S. L. Palay.     

Clustering of dendrites in the cerebral cortex begins in the embryonic cortical plate

Summary In this study, we have asked what organizational features can be detected in the embryonic rat cerebral cortex. We have found evidence using light microscopy, and scanning and transmission electron microscopy, that soon after the first cortical neurons join the cortical plate, their apical dendrites form clusters. These clusters are characterized by the close apposition of dendritic membranes, and by intermediate-type junctions. Clustering occurs within 24 h of cortical plate formation, at a time when the cortical plate is about six cell diameters thick, and before the cortex has any afferent input or the cortical plate any synapses. Thus the clustering of apical dendrites in the cortical plate appears to be a very early organizational feature in the development of the cerebral cortex.     

Perinatal subplate neuron injury: implications for cortical development and plasticity

Perinatal brain injury may result in widespread deficits in visual, motor and cognitive systems suggesting disrupted brain development. Neurosensory and cognitive impairment are observed at increasing frequency with decreasing gestational ages, suggesting a unique vulnerability of the developing brain. The peak of human subplate neuron development coincides with the gestational ages of highest vulnerability to perinatal brain injury in the premature infant. At the same time, human thalamocortical connections are forming and being refined by activity-dependent mechanisms during critical periods. Subplate neurons are the first cortical neurons to mature and are selectively vulnerable to early hypoxic-ischemic brain injury in animal models. Timing of subplate neuron death determines the resulting defect in thalamocortical development: very early excitotoxic subplate neuron death results in failure of thalamocortical innervation, while later subplate neuron death interferes with the refinement of thalamocortical connections into mature circuits. We suggest that subplate neuron injury may be a central component of perinatal brain injury resulting in specific neurodevelopmental consequences.     

Myelinated perikarya and dendrites in lateral geniculate nucleus of adult cat following chronic cortical deafferentation

Summary Chronic (one year) cortical deafferentation resulted in the appearance of myelinated neuronal perikarya and dendritic processes in the lateral geniculate nucleus (LGN) of the cat. Four per cent of all nerve cell bodies, both large and small, were observed to be covered partially or totally by compact myelin sheath. The myelination of the dendrites was confined to the most proximal portion of the processes. A comparison of the fine structural features of the myelinated cell bodies and dendrites with those from intact LGN indicate that both surviving projection neurons and local interneurons may become myelinated.It is suggested that the unorthodox myelination of nerve cell somata and dendrites is caused primarily by the massive deafferentation of the nucleus. This indicates a relationship between synaptic input and the process of myelination of the postsynaptic nerve cells.     

Perinatal death in two sibs with infantile cortical hyperostosis (Caffey disease)

We describe 2 sibs with lethal, prenatal-onset cortical hyperostosis. Antenatal sonographic diagnosis of the first sib was that of short limb dwarfism and thoracic dysplasia (nonspecific), possibly osteogenesis imperfecta. The second sib had a similar appearance on ultrasonography. The thickened, irregularly echodense diaphyses were an aid to diagnosis. Although sporadic cases and autosomal dominant inheritance have been described, an autosomal recessive cause for the lethal prenatal onset cases cannot be excluded. © 1995 Wiley-Liss, Inc.     

Subcellular plasticity of the corticotropin-releasing factor receptor in dendrites of the mouse bed nucleus of the stria terminalis following chronic opiate exposure

Chronic opiate administration alters the expression levels of the stress-responsive peptide, corticotropin-releasing factor (CRF), in the bed nucleus of the stria terminalis (BNST). This brain region contains CRF receptors that drive drug-seeking behavior exacerbated by stress. We used electron microscopy to quantitatively compare immunolabeling of the corticotropin-releasing factor receptor (CRFr) and CRF in the anterolateral bed nucleus of the stria terminalis (BSTal) of mice injected with saline or morphine in escalating doses for 14 days. We also compared the results with those in non-injected control mice. The tissue was processed for CRFr immunogold and CRF immunoperoxidase labeling. The non-injected controls had a significantly lower plasmalemmal density of CRFr immunogold particles in dendrites compared with mice receiving saline, but not those receiving morphine, injections. Compared with saline, however, mice receiving chronic morphine showed a significantly lower plasmalemmal, and greater cytoplasmic, density of CRFr immunogold in dendrites. Within the cytoplasmic compartment of somata and dendrites of the BSTal, the proportion of CRFr gold particles associated with mitochondria was three times as great in mice receiving morphine compared with saline. This subcellular distribution is consistent with morphine,- and CRFr-associated modulation of intracellular calcium release or oxidative stress. The between-group changes occurred without effect on the total number of dendritic CRFr immunogold particles, suggesting that chronic morphine enhances internalization or decreases delivery of the CRFr to the plasma membrane, a trafficking effect that is also affected by the stress of daily injections. In contrast, saline and morphine treatment groups showed no significant differences in the total number of CRF-immunoreactive axon terminals, or the frequency with which these terminals contacted CRFr-containing dendrites. This suggests that morphine does not influence axonal availability of CRF in the BSTal. The results have important implications for drug-associated adaptations in brain stress systems that may contribute to the motivation to continue drug use during dependence.     

Validity of self-report of recent opiate use in treatment setting

Self-report validity of recent drug use among heroin abusers depends on many factors including the population being studied and the setting in which the study is carried out. This study was conducted by the treating physicians to assess the self-report validity of recent heroin use by heroin dependent patients in the outdoor setting using 'thin layer chromatography' (TLC) and two highly sensitive methods of urinalysis viz. 'gas liquid chromatography' (GLC) and 'high performance liquid chromatography' (HPLC). Out of seventy-six heroin dependent patients who entered the study, 64 provided urine sample on the same day. Patients' self-report about recent opiate use was found to have a moderate agreement with urinalysis report. However, it is important to validate it with urinalysis during the treatment process because a substantial proportion of patients fails to report recent opiate use. It is recommended that all drug dependence treatment centres should be equipped with a sensitive urinalysis facility. Otherwise, the outcome of the treatment process should be considered with caution.     

Reversal of neuronal polarity characterized by conversion of dendrites into axons in neonatal rat cortical neurons in vitro

The mechanisms for the establishment and maintenance of cell polarity in neurons are not well understood. Axon regeneration from dendrites has been reported after axotomy near the cell body in vivo. We report here in vitro a reversal of neuronal polarity characterized by the conversion of dendrites into axons. We isolated neurons from the neonatal rat cerebral cortex. Neurons that exhibited an apical dendrite with a length of >100 microm were monitored for 3 days in culture. In 66% of neurons examined, a new axon, as identified by reactivity with an antibody to dephosphorylated tau or by lack of reactivity with an antibody to the a and b isoforms of microtubule-associated protein 2, appeared to form from the tip of the original dendrite. Further analysis of such neurons revealed that the distal half of the original dendrite became positive for dephosphorylated tau or negative for microtubule-associated protein 2. Time-lapse video microscopy demonstrated the conversion of the original dendrite into an axon without dendritic retraction. Axon regeneration from dendritic tips required a significantly longer time than axon regeneration from minor processes.Our observations thus demonstrate in vitro a time-consuming reversal of neuronal polarity and the conversion of a dendritic cytoskeleton into an axonal one.     

Stability of dendrites in cortical barrels of C57BL/6N mice between 4 and 45 months

Qualitative and quantitative studies of dendritic parameters were conducted on Golgi-impregnated layer IV spiny stellate neurons in the posteromedial barrel subfield (PMBSF) of somatosensory cortex of the C57B1/6N mouse. Three mice each, at 4, 12, 22, 26, 30, 36 and 45 months of age were studied. No qualitative changes were observed among animals of different ages. The quantitative data indicated that dendritic length and numbers of segments remained unchanged over all ages studied.     

Up-regulation of opiate receptors following chronic naloxone treatment in aged rats

The present study assessed whether there are age-dependent differences in up-regulation of opiate receptors following chronic naloxone treatment in mature (3 months) and aged (27 months) male Wistar rats. Half of each age group were implanted subdermally with slow-release naloxone pellets for 10 days, and half were given sham surgery. Twenty-four hours after pellet removal, the rats were decapitated and various CNS areas including spinal cord, hindbrain, midbrain, diencephalon, hippocampus, striatum, olfactory tubercles/nucleus accumbens and prefrontal cortex were dissected and assayed for [3H]naloxone binding. The results indicated that aged rats had fewer opiate receptors in the spinal cord, midbrain, striatum, and olfactory tubercle/nucleus accumbens. Despite this age-related decline in opiate receptors, aged rats showed an up-regulation response similar to mature rats in all areas except the hippocampus of the left hemisphere, where they showed enhanced up-regulation relative to mature rats. The maintained plasticity of the opioid system contrasts with findings in other receptors systems where age-related impairments of antagonist-induced up-regulation have been reported.     

Factors affecting the outcome of methadone maintenance treatment in opiate dependence

This study aimed to measure the rates of ongoing heroin abuse among patients on methadone maintenance treatment (MMT) and sought to identify patient and treatment characteristics associated with poorer outcome. The study was carried out at an outpatient drug treatment clinic and included all patients who were on the MMT during a three month period in 2004. Treatment response was measured from analysis of opiate positive urine samples. Of the 440 patients, 63% were male and their mean age was 32 years (range 17 to 52 years). 163 patients (37%) had a comorbid psychiatric illness. The average methadone dose was 74 mg. On average, 71% of urine samples were opiate negative. Shorter time in treatment (less than 24 months), lower dose of methadone, cocaine abuse and intermittent benzodiazepine abuse were each found to be significantly associated with lower rates of opiate abstinence. Outcomes were not associated with gender, age and accessing counselling. Dual diagnosed patients tended to have higher rates of abstinence (p = 0.08). MMT clients who abuse cocaine and benzodiazepines are at increased risk of continuing opiate abuse. Higher doses of methadone might be necessary to prevent illicit opiate abuse.     

Perinatal MSG treatment attenuates fasting-induced bradycardia and metabolic suppression

We studied the effect of arcuate nucleus (ARC) lesions induced pharmacologically by the perinatal treatment of monosodium l-glutamate (MSG) on the cardiovascular, metabolic, and behavioral responses to fasting. Saline and MSG-treated male Sprague-Dawley rats were instrumented with telemetry devices for measurement of mean arterial pressure (MAP) and heart rate (HR) and housed in room calorimeters at an ambient temperature (T(a)) of 23 degrees C for assessment of oxygen consumption (VO(2)). At baseline, controls and MSG-treated rats had similar MAP (control=95+/-4; MSG=91+/-2 mmHg), HR (control=323+/-4; MSG=324+/-2 bpm), and VO(2) (control=8.7+/-0.3; MSG=8.6+/-0.2 ml/min). There were no differences in fasting-induced reductions in body weight or in food intake upon refeeding. MSG-treatment significantly attenuated fasting-induced reductions in HR and VO(2). This effect was specific to reduced caloric availability, as MSG-treated rats exhibited intact capacity to both increase and decrease HR and VO(2) in response to cold (T(a)=15 degrees C) and to thermoneutrality (T(a)=30 degrees C). Additional studies were performed in saline- and MSG-treated rats chronically treated with beta(1)-adrenergic receptor blockade (atenolol) prior to and during fasting. In controls, the cardiovascular responses to fasting during beta(1)-blockade were blunted and generally mimicked the effects of MSG-treatment, while beta(1)-blockade had no additional effect on MSG-treated rats. The results are consistent with the hypothesis that ARC neuronal signaling is requisite for intact homeostatic responses to fasting and may participate in fasting-induced withdrawal of cardiac sympathetic activity.     

Carboplatin delays mammary cancer 4T1 growth in mice

Carboplatin is commonly used to treat a variety of tumors. We investigated the effects of carboplatin (100 mg/kg) in the development and metastatic dissemination of the 4T1 mice mammary carcinoma. Carboplatin was able to reduce tumor volume and the number of lung metastases in 50% compared to the control animals. Mitotic and apoptotic indices were also decreased by the treatment. Assessment of the vascularization of the tumors revealed a significant decrease in blood vessel formation by carboplatin. A decrease in nuclear positivity of CDC47 and cyclin D1 was observed in the group treated with carboplatin when compared to the control group. Positivity for p53 was observed in the control group (2/28; 5%) and the treated group (5/71; 4%). Carboplatin has been demonstrated to be an efficient regulator of 4T1MMT growth and dissemination. The action of this chemotherapeutic agent seems to be related to the induction of apoptosis and inhibition of angiogenesis and cell proliferation.     

Perinatal development of the rat kidney: Apoptosis and epidermal growth factor

ABSTRACT  Localization of apoptotic cells in the kidney of perinatal rats was examined by the terminal deoxynucleotidyl transferase-mediated d-UTP-biotin nick end labeling (TUNEL) method and electron microscopy. Perinatal changes in the percentage of kidney cells with DNA fragmentation were determined by flow cytometric analysis. Through observation of two successive sections, the relationship between the localization of the epidermal growth factor receptor (EGFR) positive cells and TUNEL positive cells in the kidney was determined. From fetal day 18 to neonatal day 5, TUNEL positive cells were noted in immature glom-eruli, collecting ducts and interstitium. Electron microscopically, chromatin condensed nuclei and apoptotic bodies were seen in the same tissue component as the TUNEL positive cells. The percentage of DNA fragmented cells significantly increased from fetal days 18 to 20 and significantly decreased from fetal days 20 to 22, while they still remained low in the neonatal period. The TUNEL positive cells in immature glom-eruli and collecting ducts were not reactive to the EGFR antibody. The TUNEL positive cells were not observed in the proximal tubular cells, which were positive to EGFR antibody. These results indicate that apoptotic cells are present in the kidney throughout the perinatal period in the rat and that EGF plays an important role in perinatal development of the rat kidney.