Biomedical subjects

A Barnea

Publications and source records attributed to A Barnea.

At least 19 recordsLinked to original sources

PubMed2006

An outbreak of leptospirosis among Israeli troops near the Jordan River.

An outbreak of leptospirosis that involved 7 of a team of 27 Israeli troops occurred following a military exercise in northern Israel near the Jordan River. The organism implicated in the outbreak was Leptospira interrogans serovar Hardjo. The clinical course was uncomplicated and all patients fully recovered. There were no cases of asymptomatic infection. Military personnel should be recognized as having an occupational risk for contracting leptospirosis, especially when military activity takes place near natural water sources inhabited by cattle, taking into account the local epidemiology of this disease. Moreover, outbreaks among military personnel may serve as a sentinel for leptospiral illness in areas in which civilian exposure takes place, such as the Jordan River, which is an important site that involves immersion in the context of both pilgrimage and civilian recreational activities."Bathe and you will become clean. So he went down and immersed himself seven times in the Jordan, as Elisha had told him to do. And his flesh became clean once more like the flesh of a small child."II Kings 5:14.

Adult↗

PubMed2005

Effect of neurofeedback on hemispheric word recognition.

We applied SMR/theta neurofeedback (NF) training at central sites of 20 Israeli children aged 10-12 years, half boys and half girls. Half of the subjects received C3 training and the other half C4 training, consisting of 20 half-hour sessions. We assessed the effects of training on lateralized lexical decision in Hebrew. The lateralized lexical decision test reveals an independent contribution of each hemisphere to word recognition (Barnea, Mooshagian, & Zaidel, 2003). Training increased accuracy and sensitivity. It increased left hemisphere (LH) specialization under some conditions but it did not affect interhemispheric transfer. Training did affect psycholinguistic processing in the two hemispheres, differentially at C3 and C4. Training also increased hemispheric independence. There were surprising sex differences in the effects of training. In boys, C4 training improved LH accuracy, whereas in girls C3 training improved LH accuracy. The results suggest that the lateralized NF protocol activates asymmetric hemispheric control circuits which modify distant hemispheric networks and are organized differently in boys and girls.

Analysis of Variance↗

PubMed2004

New approach for serological testing for leptospirosis by using detection of leptospira agglutination by flow cytometry light scatter analysis.

Leptospirosis is considered an important reemerging infectious disease worldwide. The standard and most widespread method for the diagnosis of leptospirosis is the microscopic agglutination test (MAT). This test is laborious and time-consuming, and the interpretation of the results is subjective. In the present work we describe an application of flow cytometry (FCM) as a tool for the serological diagnosis of leptospirosis. The analysis is based on the sensitivity of FCM to the size and shape of the bacteria analyzed by measurement of light scatter parameters: forward scatter (FSC) and side scatter (SSC). The addition of positive serum to an infecting leptospiral serovar results in a shift of the light scatter parameter to a different location with higher FSC and SSC values, indicating the formation of leptospiral aggregates. By using immunofluorescent staining, we have shown that the large particles formed are the agglutinated leptospires. Quantification of the agglutination process has been achieved by calculating an agglutination factor (Af), based on changes in the light scatter parameters measured by FCM. Af enables us to determine the specificity of the serological reaction of the patient serum with each leptospiral serovar. In this work, 27 serum samples from 18 leptospirosis patients were tested by both the MAT and the FCM techniques, in which each serum sample was tested against 13 serovars. Twenty-six human serum samples derived from patients with a variety of other defined illnesses were used as negative controls and enabled us to define the Af threshold value as < 9.3 for negative patients, while any value higher than that would be a positive result for leptospirosis. Compared to MAT, the FCM technique was found to be more specific and sensitive, especially in identifying the serogroup in the acute phase of the disease. The whole process was found to be rapid and took less than 1.5 h. Moreover, FCM analysis is objective and can be automated for the handling of large numbers of samples.

Agglutination↗

PubMed2002

Social change affects the survival of new neurons in the forebrain of adult songbirds.

Many new neurons are added to the adult avian brain. Most of them die 3-5 weeks after they are born (Nature (Lond.) 335 (1988) 353; J. Comp. Neurol 411 (1999) 487). Those that survive replace, numerically, older ones that have died (Neuron 25 (2000) 481). It has been suggested that the new neurons enhance the brain's ability to acquire new long-term memories (review in Sci. Am. 260 (1989) 74). If so, perhaps an increase in social complexity affects the survival of new neurons in a social species. To test this hypothesis, we treated adult zebra finches (Taeniopygia guttata) with [3H]-thymidine immediately before introducing them into one of three different social environments that differed in complexity and killed them 40 days later. There was a significant difference between experimental groups in the number of [3H]-labeled neurons in neostriatum caudale (NC), high vocal center (HVC) and Area X, three forebrain regions that are involved in vocal communication. In these regions, birds placed in a large heterosexual group had more new neurons than birds kept singly or as male-female pairs. Regulation of new neuron survival by extent of circuit use may be a general mechanism for ensuring that neuronal replacement is closely attuned to environmental change.

Animals↗

PubMed2002

Epidemiological and clinical features of leptospirosis in Israel.

The epidemiology and clinical features of 46 cases of human leptospirosis diagnosed in Israel between 1986 and 1999 were analysed. The median patient age was 37.5 years (range, 16-85 years), and the male/female ratio was 43/3. The most common serogroup found was Leptospira icterohaemorrhagiae. The disease was associated with jaundice in 71% of cases, acute renal failure in 62%, rhabdomyolysis in 52%, pancytopenia in 28%, respiratory failure in 14% and disseminated intravascular coagulation in 5%. Leptospirosis occurs sporadically throughout the year, peaking during the summer months. A shift occurred from predominantly agriculture-related serogroups in the 1970s to urban-related serogroups during the study period reported, with Leptospira icterohaemorrhagiae being the dominant serogroup.

Adolescent↗

PubMed2001

Induction of functional and morphological expression of neuropeptide Y (NPY) in cortical cultures by brain-derived neurotrophic factor (BDNF): evidence for a requirement for extracellular-regulated kinase (ERK)-dependent and ERK-independent mechanisms.

Previous studies have demonstrated that brain-derived neurotrophic factor (BDNF) induces expression of neuropeptide Y (NPY) neurons in aggregate cultures derived from the fetal rat cortex. Using BDNF induction of NPY production and neurite extension of NPY neurons as functional and morphological criteria, respectively, we addressed the question: Does BDNF activate the extracellular-regulated kinase (ERK) pathway and if so, is activated (phosphorylated, P)-ERK required for the induction of both the functional and morphological expression of NPY? BDNF led to a rapid (30 min) and sustained (6 h) phosphorylation of ERK. PD98059 (PD, a specific inhibitor of the ERK kinase MEK), drastically inhibited, LY294002 (LY, a specific inhibitor of phosphatidylinositol-3-kinase, PI-3K) partially inhibited, and GF 109203X (GF, a specific inhibitor of protein kinase C) did not inhibit phosphorylation of ERK. A 24-h exposure to BDNF led to approximately 2-fold increase in the total culture content of NPY ( approximately 60% of which was secreted and approximately 40% remained in the aggregates) and to an abundance of neurite-bearing NPY neurons. BDNF-induced NPY produced and secreted into the medium was inhibited 73% by PD, 52% by LY and not at all by GF. In contrast, BDNF-induced NPY produced and sequestered in the aggregates was not inhibited by any of these inhibitors, suggesting a role for the ERK pathway in induced secretion of NPY. PD or LY did not inhibit BDNF-induced abundance of neurite-bearing NPY neurons. K252a (an inhibitor of TrkB-tyrosine kinase) abolished all the effects of BDNF assessed in our cultures. In summary, we demonstrate that TrkB-mediated activation of the ERK pathway is preferentially required for BDNF induction of NPY produced and secreted but not for the induction of the expression of neurite-bearing NPY neurons. Thus, BDNF induction of the functional and morphological expression of NPY is brought about by ERK-dependent and ERK-independent mechanisms.

Animals↗

PubMed2001

Female odors lead to rapid activation of mitogen-activated protein kinase (MAPK) in neurons of the vomeronasal system.

Pheromonal mediation of reproductive function proceeds along a neuroanatomical pathway that connects the vomeronasal organ (VNO) at the periphery with downstream target-sites in the amygdala and hypothalamus. The MAPK pathway is a prominent cascade linking receptor activation to induction of effectors such as c-Fos. We addressed the question: Does a specific pheromone stimulus lead to activation (phosphorylation, P) of MAPK in the VN system of the male mouse? Phosphorylation of MAPK in the VN system was evaluated 15-30 min and 1.5-2 h after exposure to female odors, using immunocytochemical techniques. A rapid and transient cytoplasmic expression of PMAPK was noted in the VNO with a unique distribution of the expressing neurons in columns extending over the entire basal to apical axis. A rapid and sustained expression was noted in most amygdaloid and hypothalamic VN target-sites and also in a few amygdaloid and hypothalamic sites outside the traditional VN system. The extent of expression and the subcellular compartmentalization (nucleus, cytoplasm, processes) of PMAPK were region-dependent. Of the VN target-sites, the accessory olfactory bulb (AOB) stood out in the lack of expression of PMAPK, in the high expression of the MAPK enzyme itself and in the massive of expression of c-Fos. This expression profile implicates another pathway(s) in mediating VNO signaling to the AOB. Our results are the first to demonstrate the use of PMAPK to trace functional pathways. Based on the wide cellular and intracellular expression of phosphorylated MAPK in the VN system, we propose that the MAPK pathway plays an important role in mediating female pheromone signaling in the male mouse.

Amygdala↗

PubMed2001

Interleukin-1beta induces expression of neuropeptide Y in primary astrocyte cultures in a cytokine-specific manner: induction in human but not rat astrocytes.

Previous studies have demonstrated that astrocyte cultures express neuropeptide Y (NPY) in a regulated manner, namely, phorbol ester leads to an increase in proNPY-mRNA and NPY production. In this respect, the behavior of astrocytes derived from the human fetal or rat neonatal brain is similar (Regul. Pept. 75 (1998) 293). Since astrocytes can be exposed to high levels of IL-1beta, we addressed the question: Does IL-1beta regulate NPY expression by the astrocytes? Primary astrocytes derived from the human fetal or rat neonatal cortex were cultured in serum-free medium. IL-1beta, but not IL-6 or TNF-alpha, led to an increase in NPY production dose-dependently. IL-1beta action manifested in the human but not in the rat astrocytes and it was completely abolished by IL-1 receptor antagonist. The responsiveness to IL-1beta did not diminish upon sub-culture of the astrocytes (five passages). In addition, IL-1beta led to an increase in the abundance of proNPY-mRNA, which was preceded by a rapid and transient increase in cFos-mRNA and a rapid and sustained increase in JunB-mRNA. In contrast to cFos/JunB, IL-1beta did not alter the abundance of cJun-mRNA. In summary, we demonstrate that IL-1beta induction of NPY expression in astrocytes is species- and cytokine-specific and that IL-1 receptor is involved. Moreover, induction of NPY expression is preceded by a rapid increase in the expression of two transcription factors (cFos, JunB) that have been previously (Oncogene 9 (1994) 2369; J. Neurochem. 70 (1998) 1887) implicated in transcriptional regulation of the human NPY gene.

Animals↗

PubMed1999

Evidence for a synergistic effect of the HIV-1 envelope protein gp120 and brain-derived neurotrophic factor (BDNF) leading to enhanced expression of somatostatin neurons in aggregate cultures derived from the human fetal cortex.

Changes in the expression of somatostatin (SRIF) have been observed in the brains of HIV encephalitis. Since gp120 is thought to play a major role in AIDS-associated abnormalities in the brain, we addressed the question: Does gp120 alter the functional expression of human fetal SRIF neurons in culture and if so, is this effect fetal-age dependent? Aggregate cultures, obtained from cortices of nine fetuses (14.9-20.7 weeks), were exposed for 7 days to BDNF or BDNF+gp120; BDNF induced production of SRIF during the subsequent 24-48 h was assessed. Similar effects of BDNF and gp120 were observed in the 9 brain-cultures. A 7-day exposure to BDNF alone led to a significant increase in SRIF production (p=0.014), whereas exposure to gp120 alone did not. Co-exposure to BDNF and gp120 led to an increase in BDNF-induced SRIF production which was significantly greater than that after BDNF alone (p=0.006). These effects were BDNF- and gp120-dose dependent and they were not accompanied by changes in DNA content of the aggregates nor in lactate dehydrogenase activity in the medium; indicating that gp120 did not lead to a major loss of cell integrity. These results are consistent with a synergistic effect of BDNF and gp120 leading to enhanced functional expression of the signalling pathway(s) mediating BDNF induction of SRIF production; an effect expressed by fetal brains throughout the 2nd trimester of gestation. Thus, this culture system can serve as a model to study the mechanism(s) underlying the early interactions between gp120 BDNF in the developing human brain.

Brain-Derived Neurotrophic Factor↗

PubMed1999

An improved method for dissociation and aggregate culture of human fetal brain cells in serum-free medium.

Moscona, in the early sixties [A.A. Moscona, Recombination of dissociated cells and the development of cell aggregates, in: B.M. Willmer (Ed.), Cells and Tissues in Culture, Academic Press, New York, 1965, pp. 489-529.] [16], discovered that aggregation of dissociated cells is a property of embryonal cells. Several features of the aggregate culture system are particularly attractive for the conduct of biochemical and molecular studies on the human fetal brain. (i) All the pertinent procedural parameters can be readily controlled and standardized, resulting in a consistently reproducible system suitable for quantitative analyses. (ii) Neuronal enriched aggregates can be readily obtained, with minimal neurotoxicity. (iii) Aggregates can be easily harvested for biochemical and molecular studies. Aggregate cultures, generated from rodent fetal brains, have been extensively utilized as a tool to study regulation of aminergic neurons [P. Honegger, E. Richelson, Biochemical differentiation of mechanically dissociated brain in aggregating cell culture, Brain Res. 109 (1976) 335-354; P. Honegger, E. Richelson, Biochemical differentiation of aggregating cell cultures of different fetal rat brain regions, Brain Res. 133 (1977) 329-339.] [11,12] and peptidergic neurons (neuropeptide Y (NPY) and somatostatin (SRIF) [A. Barnea, E. Anthony, G. Lu, G. Cho, Morphological differentiation of neuropeptide Y neurons in aggregate cultures of dissociated fetal cortical cells: a model system for glia-neuron paracrine interactions, Brain Res. 625 (1993) 313-322; A. Barnea, G. Cho, G. Lu, M. Mathis, Brain-derived neurotrophic factor induces functional expression and phenotypic differentiation of cultured fetal neuropeptide Y producing neurons, J. Neurosci. Res. 42 (1995) 638-647; A. Barnea, A. Hajibeigi, G. Cho, P. Magni, Regulated production and secretion of immunoreactive neuropeptide Y by aggregating fetal brain cells in culture, Neuroendocrinology 54 (1991) 7-13; P. Magni, A. Barnea, Forskolin and phorbol ester stimulation of neuropeptide Y (NPY) production and secretion by aggregating fetal brain cells in culture: evidence for regulation of NPY biosynthesis at transcriptional and posttranscriptional levels, Endocrinology 130 (1992) 976-984.]) [4-6,14]. However, very few studies have utilized this system to study regulatory processes of human fetal neurons/glia [M. McCarthy, L. Resnik, F. Taub, R.V. Stewart, R.D. Dix, Infection of human neural cell aggregate cultures with a clinical isolate of cytomegalovirus, J. Neuropathol. Exp. Neurol. 50 (1991) 441-450; L. Pulliam, M.E. Berens, M.L. Rosenblum, A normal human brain cell aggregate model for neurobiological studies, J. Neurosci. Res. 21 (1988) 521-530.] [15,17]. In a series of studies in our laboratory [N. Aguila-Mansilla, A. Barnea, Human fetal brain cells in aggregate culture: a model system to study regulatory processes of the developing human neuropeptide Y (NPY) producing neuron, Int. J. Dev. Neurosci. 14 (1996) 531-539; A. Barnea, N. Aguila-Mansilla, H.T. Chute, A.A. Welcher, Comparison of neurotrophin regulation of human and rat neuropeptide Y (NPY) neurons: induction of NPY production in aggregate cultures derived from rat but not from human fetal brains, Brain Res. 732 (1996) 52-60; A. Barnea, N. Aguila-Mansilla, G. Lu, R.H. Ho, Opposite effects of astrocyte-derived soluble factor(s) on the functional expression of fetal peptidergic neurons in aggregate cultures: enhancement of neuropeptide Y and suppression of somatostatin, J. Neurosci. Res. 50 (1997) 605-617; A. Barnea, J. Roberts, R.H. Ho, Evidence for a synergistic effect of the HIV-1 envelope protein gp120 and brain-derived neurotrophic factor (BDNF) leading to enhanced expression of somatostatin neurons in aggregate cultures derived from the human fetal cortex, Brain Res. 815 (1999) 349-357.] [1-3,7], we have established a human-derived aggregate culture system, maintained in serum-free medium for up to 28 days, in which expression

Brain↗

PubMed1999

The effect of pyrazine odor on body weight and the weight of various organs in chicks (Gallus gallus domesticus).

Embryonic and posthatch long-term exposure to the odor of 2-methoxy-3-isobutyl-pyrazine (2M3IP) was examined for its potential physiological consequences as reflected in changes in BW and organ weights in domestic chicks (Gallus gallus domesticus). Experiments were run from Day 1 of incubation to the age of 3 wk with a total of 360 fertile chicken eggs. The experimental design consisted of four treatment groups: PP chicks were exposed to 2M3IP during both incubation and posthatch rearing; PC chicks were exposed to 2M3IP during incubation only; CP chicks were exposed to 2M3IP during rearing period only; CC control chicks were not exposed to 2M3IP. Chicks were weighed immediately after hatch and at 3 wk of age, when they were necropsied. Various organs (thyroid, adrenal, testes, comb, liver, spleen, abdominal fat, and the bursa of Fabricius) were removed and weighed. Body weights of both sexes in the PP group were reduced. This reduction was significant in males relative to both CP and CC groups and in females only relative to the CP group. Effects of 2M3IP exposure on the examined organs were as follows: in males, adrenal gland weight significantly increased in the PP group vs all other groups. No weight differences were found between the other inspected organs among the four treatments. In females, comb weight significantly decreased compared with the rest of the groups when 2M3IP exposure occurred during incubation (PC). Further investigation is needed to study the mechanisms that underlie the differential effects of pyrazine odor on male and female chicks.

Adipose Tissue↗

PubMed1998

Evidence for regulated expression of neuropeptide Y gene by rat and human cultured astrocytes.

A series of studies from our laboratory have established that fetal rat and human neuropeptide Y (NPY) cortical neurons in aggregate cultures are differentially regulated. In a preliminary study we found that primary astrocytes produce substantial amounts of immunoreactive (IR) NPY. We addressed the question: Is astrocyte production of NPY-IR a regulated process? The effects of brain-derived neurotrophic factor (BDNF, 50 ng/ml), basic fibroblast growth factor (bFGF), substance P (1 microM), forskolin (10 microM), or phorbol 12-myristate-13-acetate (PMA, 20 nM) on NPY-IR production was tested on rat and human primary astrocyte cultures. Of these agents, PMA and bFGF markedly induced NPY-IR production by rat as well as human astrocytes, forskolin induced NPY-IR production by human but not rat astrocytes, and neither BDNF nor substance P induced NPY-IR production by rat or human astrocytes. The molecular size of PMA-induced NPY-IR was found to be consistent with that of proNPY. Moreover, PMA induced the accumulation of mRNA corresponding in size to the neuronal NPY-mRNA. Immunocytochemical analysis of human post-mortem neocortex revealed co-existence of NPY-IR with astrocyte markers. These results indicate that cultured astrocytes express NPY gene in a regulated manner and they support our proposition that in situ reactive astrocytes may express NPY gene under some physiological/pathological conditions.

Animals↗

PubMed1998

Phonological and orthographic processing of Hebrew words: electrophysiological aspects.

Brain activity among 15 male, college-level, normal readers in Israel was examined during phonological and orthographic word-recognition tasks. Both electrophysiological (event-related potentials, or ERPs) and behavioral measures were obtained. Data indicated that (a) behavioral accuracy was almost perfect for all the experimental tasks, and (b) although P200 and N400 ERP components were elicited in the experimental tasks, the latencies of those components were significantly longer and their amplitudes significantly higher in the phonological task. Variations in vowel information had no effect on word recognition in either type of task. The results suggest that among skilled readers of Hebrew, phonological processing during word recognition may be more effortful and may demand greater cognitive resources than orthographic processing. Furthermore, the additional phonological information represented in vowels appears to contribute little to word recognition in this population. These findings support earlier research on skilled reading in Hebrew as well as current theoretical models of reading.

Adolescent↗

PubMed1997

Opposite effects of astrocyte-derived soluble factor(s) on the functional expression of fetal peptidergic neurons in aggregate cultures: enhancement of neuropeptide Y and suppression of somatostatin.

Previous studies established that fetal rat and human neuropeptide Y (NPY) cortical neurons in aggregate cultures are differentially regulated. Whereas brain-derived neurotrophic factor (BDNF) or phorbol 12-myristate-13-acetate (PMA) induces NPY production in rat cultures, only PMA does so in human cultures. We addressed these questions: 1) Do soluble products of rat or human astrocytes (conditioned medium; rCM and hCM, respectively) enhance the functional expression of cultured NPY neurons and if so, do they enhance the expression of somatostatin (SRIF) neurons as well? 2) Is the NPY-enhancing activity (EA) in the CM species specific? rCM enhanced (approximately 2-fold) both basal and BDNF-stimulated production of NPY and coculture of rat aggregates and astrocytes did not prevent this NPY-EA. Likewise, the hCM enhanced (approximately 2.5-fold) basal and PMA-stimulated production of NPY by human aggregates. Moreover, the hCM enhanced NPY production by rat aggregates and rCM enhanced NPY production by human aggregates. In addition, rCM and hCM each enhanced BDNF-, forskolin-, or PMA-stimulated NPY production by rat aggregates. Under each of the above conditions, the rCM/hCM suppressed (approximately 50%) production of SRIF by rat aggregates. In summary, secretory products of rat and human astrocytes exert opposite effects on the functional expression of NPY and SRIF neurons in culture: enhancement of NPY and suppression of SRIF. By the criteria evaluated in this study, these astrocyte-derived activities do not exhibit species specificity.

Animals↗

PubMed1997

Differential potencies of cocaine and its metabolites, cocaethylene and benzoylecgonine, in suppressing the functional expression of somatostatin and neuropeptide Y producing neurons in cultures of fetal cortical cells.

Using aggregate cultures derived from 17-day-old fetal rat cortex, we addressed the question: Does cocaine alter the functional expression of neuropeptide Y (NPY) and somatostatin (SRIF) neurons and, if so, are cocaethylene (CE) and benzoylecgonine (BZE) as active as cocaine? NPY/SRIF production in response to brain-derived neurotrophic factor (BDNF) or phorbol-12-myristate-13-acetate (PMA) was used as a functional criterion. A 5-day exposure to cocaine did not affect basal or stimulated (BDNF or PMA) production of NPY but it markedly suppressed BDNF- or PMA-stimulated production of SRIF. Exposure to CE led to a drastic suppression of basal as well as stimulated (BDNF or PMA) production of both NPY and SRIF. These effects of cocaine and CE were concentration dependent (1-100 microM). BZE did not alter any of these functional parameters. Next, we evaluated the fate of cocaine, CE, and BZE in the culture medium. Cocaine was converted to BZE, whereas BZE was not converted to cocaine. CE was converted to cocaine and BZE, with substantial amounts of cocaine and CE remaining in the medium after 72 hr (approximately 20% each). In summary, cocaine, CE, and BZE exhibited differential potencies in suppressing the expression of cultured NPY and SRIF neurons: CE was more potent than cocaine and BZE was inactive. SRIF neurons were more susceptible than NPY neurons to the effects of cocaine. The higher potency of CE may be due to a property of the compound and/or to CE serving as a source for a slow, continuous formation of cocaine by the brain cells themselves.

Animals↗

PubMed1997

Elimination of tritiated thymidine from birds.

The kinetics with which tritiated thymidine is eliminated from birds and the concentration of radioactivity remaining in the carcass after 350-430 h were measured. Birds injected with tritiated thymidine eliminated 98% of the radioactivity injected within 28 h. Ninety-eight percent was identified in the excreta, and less than 2% of the radioactivity injected remained in the birds 28 h after injection.

Animals↗

PubMed1996

Comparison of neurotrophin regulation of human and rat neuropeptide Y (NPY) neurons: induction of NPY production in aggregate cultures derived from rat but not from human fetal brains.

Previous studies established that brain-derived neurotrophic factor (BDNF) induces neuropeptide Y (NPY) production and accumulation of NPY-mRNA in cultures of rat fetal brain tissues. In this study, we addressed the question: Are cultured human NPY neurons regulated by BDNF and/or by another member of the neurotrophin (NT) family of growth factors? Using aggregate cultures derived from human fetal cortical hemispheres, we assessed the effect of BDNF on NPY production varying the following experimental conditions: fetal and culture age; medium composition (with and without serum), dose and duration of exposure to BDNF, and neurotrophin species tested (BDNF, NT-4/5, NT-3 or NGF). Under none of these conditions did BDNF, NT-4/5, NT-3 or NGF induce an increase in NPY production. This was in contrast to forskolin + phorbol 12 myristate 13-acetate (PMA) which were highly effective in inducing NPY production, verifying that expression of NPY is a regulated process in these cultures. None of these neurotrophins enhanced the response to forskolin + PMA. By comparison, using aggregate cultures derived from rat fetal cortices, BDNF and NT-4/5 were equipotent in inducing NPY production but NT-3 and NGF were essentially ineffective. Moreover, the effects of BDNF or NT-4/5 and forskolin + PMA on NPY production were additive, indicating the involvement of distinct intracellular signalling pathways. Western blot analyses of human- and rat-derived aggregates indicated the presence of full-length Trk receptors which are tyrosine-phosphorylated in response to either BDNF, NT-4/5 or NT-3. Primary cultures of astrocytes (rat as well as human) were devoid of a functional TrkB receptor, strongly suggesting a neuronal expression of TrkB in the aggregates. Thus, a functional TrkB receptor is expressed by both the human and rat aggregates, but only the rat aggregates responded to BDNF or NT-4/5. These results are consistent with a difference in a post TrkB-receptor event(s) mediating BDNF action in the cultured human and rat fetal NPY neurons.

Abortion, Induced↗

PubMed1996

Recruitment and replacement of hippocampal neurons in young and adult chickadees: an addition to the theory of hippocampal learning.

We used [3H]thymidine to document the birth of neurons and their recruitment into the hippocampal complex (HC) of juvenile (4.5 months old) and adult blackcapped chickadees (Parus atricapillus) living in their natural surroundings. Birds received a single dose of [3H]thymidine in August and were recaptured and killed 6 weeks later, in early October. All brains were stained with Cresyl violet, a Nissl stain. The boundaries of the HC were defined by reference to the ventricular wall, the brain surface, or differences in neuronal packing density. The HC of juveniles was as large as or larger than that of adults and packing density of HC neurons was 31% higher in juveniles than in adults. Almost all of the 3H-labeled HC neurons were found in a 350-m-wide layer of tissue adjacent to the lateral ventricle. Within this layer the fraction of 3H-labeled neurons was 50% higher in juveniles than in adults. We conclude that the HC of juvenile chickadees recruits more neurons and has more neurons than that of adults. We speculate that juveniles encounter greater environmental novelty than adults and that the greater number of HC neurons found in juveniles allows them to learn more than adults. At a more general level, we suggest that (i) long-term learning alters HC neurons irreversibly; (ii) sustained hippocampal learning requires the periodic replacement of HC neurons; (iii) memories coded by hippocampal neurons are transferred elsewhere before the neurons are replaced.

Journal Article↗