Elimination of human rabies in Goa, India through an integrated One Health approach.

Dog-mediated rabies kills tens of thousands of people each year in India, representing one third of the estimated global rabies burden. Whilst the World Health Organization (WHO), World Organization for Animal Health (OIE) and the Food and Agriculture Organization of the United Nations (FAO) have set a target for global dog-mediated human rabies elimination by 2030, examples of large-scale dog vaccination programs demonstrating elimination remain limited in Africa and Asia. We describe the development of a data-driven rabies elimination program from 2013 to 2019 in Goa State, India, culminating in human rabies elimination and a 92% reduction in monthly canine rabies cases. Smartphone technology enabled systematic spatial direction of remote teams to vaccinate over 95,000 dogs at 70% vaccination coverage, and rabies education teams to reach 150,000 children annually. An estimated 2249 disability-adjusted life years (DALYs) were averted over the program period at 526 USD per DALY, making the intervention 'very cost-effective' by WHO definitions. This One Health program demonstrates that human rabies elimination is achievable at the state level in India.

Free-roaming dog population dynamics in Ranchi, India.

Rabies causes approximately 20,000 human deaths in India each year. Nearly all of these occur following dog bites. Large-scale, high-coverage dog rabies vaccination campaigns are the cornerstone of rabies elimination strategies in both human and dog populations, although this is particularly challenging to achieve in India as a large proportion of the dog population are free-roaming and unowned. Further, little is known about free-roaming dog ecology in India which makes defining optimum vaccination strategies difficult. In this study, data collected using a mobile phone application during three annual mass vaccination and neutering (surgical sterilisation of both males and females) campaigns of free-roaming dogs in Ranchi, India (during which a total of 43,847 vaccinations, 26,213 neuter surgeries and 28,172 re-sight observations were made) were interrogated, using two novel approaches to estimate the proportion of neutered dogs that were lost from the city (assumed due to mortality or migration) between campaign years. Analysis revealed high losses of neutered dogs each year, ranging from 25.3% (28.2-22.8) to 55.8% (57.0-54.6). We also estimated that the total population declined by 12.58% (9.89-15.03) over the three-year period. This demonstrates that there is a high turnover of free-roaming dogs and that despite neutering a large number of dogs in an annual sterilisation campaign, the decline in population size was modest over a three-year time period. These findings have significant implications for the planning of rabies vaccination campaigns and population management programmes as well as highlighting the need for further research into the demographics of free-roaming, unowned dogs in India.

Timing of reproduction and association with environmental factors in female free-roaming dogs in southern India.

Annual peaks in reproductive activity have been identified in multiple domestic dog populations. However, there is little evidence to describe how these peaks may be associated with environmental factors such as daylength, which plays a well-established role in breeding patterns of seasonally-reproductive species. Data were collected 2016-2020 during 7,743 and 4,681 neuter surgeries on adult female unowned free-roaming dogs in veterinary clinics in Goa and Tamil Nadu respectively. Temperature, precipitation, relative humidity, and daylength data were gathered for time periods preceding the neuter surgery that may have influenced the likelihood of pregnancy (potential influence periods). A multivariable generalised additive model was used to assess the relationship between these factors and pregnancy. The prevalence of pregnancy varied by month in both locations indicating seasonality of reproduction in these groups. The annual pattern was more distinct in Goa with a peak in pregnancies between September and December. In Goa, decreasing daylength was associated with a higher probability of pregnancy (p = 0.040). Decreasing temperature was associated with decreasing probability of pregnancy in the Nilgiris (p = 0.034). Bitches had a median of 6 foetuses, with no evidence of seasonal variation. Environmental factors were associated with patterns of pregnancy in free-roaming dogs, however statistically-significant factors varied by geographical location. Establishing local seasonal patterns of breeding in free-roaming dogs and assessing their relationship with environmental influences is recommended to facilitate effective and efficient population management strategies, which aim to reduce conflict between human and free-roaming dog populations.

Oral bait handout as a method to access roaming dogs for rabies vaccination in Goa, India: A proof of principle study.

Rabies has profound public health, social and economic impacts on developing countries, with an estimated 59,000 annual human rabies deaths globally. Mass dog vaccination is effective at eliminating the disease but remains challenging to achieve in India due to the high proportion of roaming dogs that cannot be readily handled for parenteral vaccination. Two methods for the vaccination of dogs that could not be handled for injection were compared in Goa, India; the oral bait handout (OBH) method, where teams of two travelled by scooter offering dogs an empty oral bait construct, and the catch-vaccinate-release (CVR) method, where teams of seven travel by supply vehicle and use nets to catch dogs for parenteral vaccination. Both groups parenterally vaccinated any dogs that could be held for vaccination. The OBH method was more efficient on human resources, accessing 35 dogs per person per day, compared to 9 dogs per person per day through CVR. OBH accessed 80% of sighted dogs, compared to 63% by CVR teams, with OBH accessing a significantly higher proportion of inaccessible dogs in all land types. All staff reported that they believed OBH would be more successful in accessing dogs for vaccination. Fixed operational team cost of CVR was four times higher than OBH, at 127 USD per day, compared to 34 USD per day. Mean per dog vaccination cost of CVR was 2.53 USD, whilst OBH was 2.29 USD. Extrapolation to a two week India national campaign estimated that 1.1 million staff would be required using CVR, but 293,000 staff would be needed for OBH. OBH was operationally feasible, economical and effective at accessing the free roaming dog population. This study provides evidence for the continued expansion of research into the use of OBH as a supplementary activity to parenteral mass dog vaccination activities in India.

Investigation of short-term surgical complications in a low-resource, high-volume dog sterilisation clinic in India.

BACKGROUND: Surgical sterilisation is currently the method of choice for controlling free-roaming dog populations. However, there are significant logistical challenges to neutering large numbers of dogs in low-resource clinics. The aim of this study was to investigate the incidence of short-term surgical complications in a low-resource sterilisation clinic which did not routinely administer post-operative antibiotics. The medical records of all sterilisation surgeries performed in 2015 at the Worldwide Veterinary Service International Training Centre in Tamil Nadu, India were reviewed (group A) to assess immediate surgical complications. All animals in this group were monitored for at least 24 h post-surgery but were not released until assessed by a veterinarian as having uncomplicated wound healing. In the second part of this study from August to December 2015, 200 free-roaming dogs undergoing sterilisation surgery, were monitored for a minimum of 4-days post-surgery to further assess postoperative complications (group B). RESULTS: Surgery related complications were seen in 5.4% (95%CI, 4.5-6.5%) of the 1998 group A dogs monitored for at least 24 h, and in 7.0% (3.9-11.5%) of the 200 group B dogs monitored for 4 days. Major complications were classed as those requiring an intervention and resulted in increased morbidity or mortality. Major complications were seen in 2.8% (2.1-3.6%) and 1.5% (3.1-4.3%) of group A and B, respectively. Minor complications requiring little or no intervention were recorded for 2.6% (1.9-3.4%) for group A and 5.5% (2.8-9.6%) for group B. There was no evidence for a difference in complication rates between the two groups in a multivariate regression model. CONCLUSION: This study demonstrated that high volume, low-resource sterilisation of dogs can be performed with a low incidence of surgical complications and low mortality.

The problem of stray dogs.

The effective management of stray dogs is critically important in any rabies vaccination programme. In many rabies-endemic countries, stray dogs represent a significant proportion of both the free-roaming and total dog populations, and to ensure that rabies elimination programmes are successful, it is essential that this portion of the dog population (stray dogs) is vaccinated at high coverage. However, there are a number of challenges to managing and delivering rabies vaccinations to stray dogs. This paper will review the most pertinent issues relating to the problem of stray dogs and rabies elimination, focusing on the challenges relating to the estimation of population size, vaccination administration and vaccine coverage assessment in stray dog populations. The authors will highlight how these challenges can be overcome, notably by reviewing the census techniques that have been employed to assess stray dog populations, which then facilitate the planning and design of vaccination programmes. In addition, they discuss the range of vaccination strategies that are available and that have been used to vaccinate stray dogs and review how vaccination coverage can be assessed in this population. Finally, the benefits of population management in stray dogs through neutering programmes are reviewed. In short, this paper highlights the importance of ensuring that stray dogs, as well as owned dogs, are included in vaccination programmes and emphasises that many of the challenges related to protecting stray dogs from rabies can be overcome.

L'efficacité de la gestion des populations de chiens errants est un aspect essentiel de tout programme de vaccination contre la rage. Dans de nombreux pays où la rage est endémique, les chiens errants constituent un segment important des populations de chiens laissés en liberté et plus généralement de la population canine totale, de sorte que le succès des programmes d'élimination de la rage repose sur l'impératif d'assurer une forte couverture vaccinale au sein de cette partie de la population canine. Toutefois, s'agissant des chiens errants la gestion de la vaccination et l'administration des vaccins antirabiques présentent des difficultés particulières. Les auteurs font le point sur les principales questions posées par la problématique des chiens errants dans une perspective d'élimination de la rage, qui concernent notamment la difficulté d'évaluer la taille des populations concernées, d'administrer les vaccins dans ce cadre et d'évaluer la couverture vaccinale obtenue. Les auteurs soulignent les réponses qui peuvent être apportées à ces problèmes, en particulier en revoyant les techniques de recensement appliquées jusqu'à présent pour évaluer les populations de chiens errants, ce qui permettra ensuite de faciliter la planification et la conception des programmes de vaccination. En outre, ils examinent les différentes stratégies de vaccination mises en oeuvre en la matière et font le point sur les moyens d'évaluer la couverture vaccinale de ces populations. Enfin, ils analysent les avantages apportés par les programmes de stérilisation pour maîtriser les populations de chiens errants. En résumé, cet article met l'accent sur l'importance d'inclure les chiens errants au même titre que les chiens ayant un maître dans les programmes de vaccination et souligne que la plupart des difficultés liées à la protection des chiens errants contre la rage peuvent être résolues.

Uno de los aspectos capitales de todo programa de vacunación antirrábica es la gestión eficaz de las poblaciones de perros vagabundos. En muchos países con rabia endémica, estos perros representan un porcentaje sustancial tanto de la población canina total como de los perros en libertad. El éxito de todo programa de eliminación de la rabia pasa necesariamente por lograr una elevada cobertura de vacunación en este segmento de la población canina (los perros vagabundos). Sin embargo, la gestión y la vacunación antirrábica de los perros vagabundos presentan una serie de dificultades. Los autores pasan revista a los aspectos que más inciden en el problema de los perros vagabundos y la eliminación de la rabia, prestando especial atención a las dificultades que presentan la estimación del tamaño de la población, la administración de vacunas y el cálculo de la cobertura de vacunación de las poblaciones de perros vagabundos. Después explican la manera de superar estas dificultades, en particular describiendo las técnicas de censo empleadas para calcular el tamaño de las poblaciones, lo que a su vez facilita la concepción y planificación de programas de vacunación. Además, describen el arsenal existente de procedimientos de vacunación que se han utilizado para vacunar a los perros vagabundos y explican cómo estimar en estas poblaciones la cobertura de vacunación. Por último exponen los beneficios de gestionar las poblaciones de perros vagabundos con programas de esterilización. En resumidas cuentas, los autores recalcan aquí la importancia de que los programas de vacunación canina lleguen a los perros vagabundos, y no solo a los animales con dueño, e insisten en que muchos de los problemas que se plantean para proteger de la rabia a los perros vagabundos tienen solución.

Investigation of productivity in a south Indian Malabari goat herd shows opportunities for planned animal health management to improve food security.

Here the authors report the objective veterinary clinical measurement of productivity in a representative south Indian Malabari goat herd. The authors show failure to meet pragmatic production targets that are commensurate with the animals' genetic potential or adequate to meet the demands of global food security. The authors suggest that this situation may have arisen as a consequence of animal husbandry constraints and protein undernutrition and imply the involvement of nematode parasitism. Benzimidazole resistance was detected in Haemonchus species, showing the need for better understanding of the principles of sustainable helminth parasite control within the southern Indian context. This study highlights the need to understand the true costs of goat production in seasonally resource-poor environments, while also considering its impact on the overall ecosystem in which the animals are placed. They conclude that pragmatic opportunities for improvements in goat production efficiency lie in the development of problem-focused planned animal health and nutrition management.

High-affinity immunoglobulin E receptor expression is increased in large and small airways in fatal asthma.

BACKGROUND: IgE and its high-affinity receptor FcɛRI play an important role in allergy and asthma. The distribution of FcɛRI expression in the airways and within the airway wall, however, is largely unknown. OBJECTIVE: In this study, we aimed to map the distribution of FcɛRI in different layers of large airways (LA) and small airways (SA) in lung tissue from non-smoking and smoking patients who died of asthma [fatal asthma (FA)] and non-smoking controls (CTR). METHODS: Postmortem lung tissue from 24 cases of non-smoking FA, 13 smoking FA patients and from 19 subjects who died of non-pulmonary causes (CTR) was immunohistochemically stained for FcɛRI and AA1 (mast cell tryptase marker). The expression of these markers was analysed in inner, muscle, and outer layers of both LA and SA by image analysis. RESULTS: FcɛRI expression was higher in non-smoking and smoking FA compared with CTR in the inner and outer layer of SA. In the outer layer of LA, FcɛRI expression was higher in non-smoking FA compared with CTR. AA1 was higher in non-smoking FA compared with smoking FA and CTR in the outer layer of the SA, which was correlated with FcɛRI in this layer. CONCLUSION: Our results show that the expression of FcɛRI is higher in both LA and SA in FA compared with CTR. These differences are predominantly found in the outer layer where they can be attributed in part to the increased mast cell numbers. These results indicate an increased capacity to mount IgE-mediated reactions in FA, both in LA and SA.

p75NTR independent oligodendrocyte death in cuprizone-induced demyelination in C57BL/6 mice.

Feeding C57Bl/6 J mice the copper chelator cuprizone leads to selective apoptosis of mature oligodendrocytes and concomitant demyelination predominantly in the corpus callosum. The process of oligodendrocyte apoptosis in this animal model for multiple sclerosis (MS) involves early microglial activation, but no infiltration of T-lymphocytes. Therefore, this model could mimic early stages of oligodendrocyte degeneration Affected oligodendrocytes express the common neurotrophin receptor, p75(NTR), a 'stress-receptor' which under certain circumstances can induce apoptosis. Only affected oligodendrocytes in MS lesions and MS animal models express this receptor. In order to study the significance of p75(NTR) in the fate of oligodendrocytes, we have exposed wild-type as well as p75(NTR)-knockout mice to a 0.2% (w/w) cuprizone diet and performed a comparative immunohistochemical analysis of the corpus callosum at various time points. Surprisingly, our results show that the absence of p75(NTR) did not alter cuprizone-induced oligodendrocyte death (and subsequent de- or remyelination). Apparently, intracellular apoptosis pathways in adult oligodendrocytes do not require p75(NTR) activated signal transduction in the absence of T-lymphocytes and T-lymphocyte derived cytokines.

A serine protease is involved in the initiation of DNA damage-induced apoptosis.

Caspases are considered to be the key effector proteases of apoptosis. Initiator caspases cleave and activate downstream executioner caspases, which are responsible for the degradation of numerous cellular substrates. We studied the role of caspases in apoptotic cell death of a human melanoma cell line. Surprisingly, the pancaspase inhibitor zVAD-fmk was unable to block cleavage of poly(ADP-ribose) polymerase (PARP) after treatment with etoposide, while it did prevent DEVDase activity. It is highly unlikely that caspase-2, which is a relatively zVAD-fmk-resistant caspase, is mediating etoposide-induced PARP cleavage, as a preferred inhibitor of this caspase could not prevent cleavage. In contrast, caspase activation and PARP degradation were blocked by pretreatment of the cells with the serine protease inhibitor 4-(2-aminoethyl)benzenesulfonyl fluoride (AEBSF). We therefore conclude that a serine protease regulates an alternative initiation mechanism that leads to caspase activation and PARP cleavage. More importantly, while zVAD-fmk could not rescue melanoma cells from etoposide-induced death, the combination with AEBSF resulted in substantial protection. This indicates that this novel pathway fulfills a critical role in the execution of etoposide-induced programmed cell death.

Bcl-2 is a monomeric protein: prevention of homodimerization by structural constraints.

The pro-apoptotic activity of the Bcl-2 family member Bax has been shown to be facilitated by homodimerization. However, it is unknown whether Bcl-2 or Bcl-x(L) have to homodimerize to protect cells from apoptosis. Here we show by co-immunoprecipitation and FPLC analyses that while Bax multimerizes and forms heterodimers with Bcl-2, there is no evidence for Bcl-2 homodimerization, even in conditions under which Bcl-2 protects cells from apoptosis. Immunofluorescence studies confirmed that Bax can attract active, soluble Bcl-2 to mitochondrial membranes, but that nuclear/ER membrane-bound Bcl-2 was incapable of dislocating soluble Bcl-2. The failure of Bcl-2 to homodimerize is due to structural constraints as versions of Bcl-2 deleted or mutated in the BH1 and BH2 domains effectively dimerized with wild-type Bcl-2 and were dislocated by Bcl-2 inside cells. These data indicate that naturally occurring Bcl-2 does not expose protein domains that mediate homodimerization and therefore most likely acts as a monomer to protect cells from apoptosis.

The binding properties and biological activities of Bcl-2 and Bax in cells exposed to apoptotic stimuli.

The oncogene product Bcl-2 protects cells from apoptosis whereas its homolog Bax functions to kill cells. Several binding partners of Bcl-2 and Bax have been isolated, but none of them has yet provided clues as to exactly how Bcl-2 and Bax work. According to one view, Bcl-2 and Bax interact with survival and death effector molecules, respectively, and neutralize each other through heterodimerization. Alternatively, Bcl-2 requires Bax for death protection, and additional proteins bind to the heterodimer to regulate its activity. Here we used a co-immunoprecipitation strategy to distinguish between these two possibilities. We show that the Bcl-2-Bax heterodimer is maintained, and no other protein associates stably in detectable amounts with Bcl-2, Bax, or the heterodimer in anti-Bcl-2 and anti-Bax immunoprecipitates from normal cells and cells exposed to apoptotic stimuli. Analysis of cells expressing various levels of Bcl-2 and Bax, however, revealed that the degree of protection against apoptosis does not correlate with the number of Bcl-2-Bax heterodimers but the amount of Bcl-2 that is free of Bax. In addition, the survival activity of Bcl-2 is unaffected when Bax expression is ablated by an antisense strategy. Our findings suggest that the Bcl-2-Bax heterodimer is a negative regulator of death protection, and that Bcl-2 requires neither Bax nor major, stable interactions with other cellular proteins to exert its survival function. We therefore propose that Bcl-2 acts as an enzyme (capturing substrates in a transient way), as a homodi- or multimer, or through the interaction with non-proteaceous targets (lipids, ions).

Defects in the ubiquitin pathway induce caspase-independent apoptosis blocked by Bcl-2.

Apoptosis requires the activation of caspases (formerly interleukin 1beta-converting enzyme-like proteases), in particular those related to the caspase-3/7/6 subfamily. Recent data, however, revealed that, although caspase-specific inhibitors delay apoptosis, they are often incapable of preventing it. To obtain evidence for caspase-independent steps of apoptosis, we artificially created a high amount of short-lived or aberrant proteins by blocking the ubiquitin degradation pathway. A temperature-sensitive defect in the ubiquitin-activating enzyme E1 induced apoptosis independent of the activation of caspase-3 and -6 and the cleavage of their respective substrates poly(ADP-ribose) polymerase and lamin A. In addition, neither the caspase 3/7-specific inhibitor N-benzyloxycarbonyl-Asp-Glu-Val-Asp-fluoromethylketone nor the general caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone were capable of blocking this type of cell death. By contrast, Bcl-2 overexpression effectively protected cells from apoptosis induced by a defect in the E1 enzyme at the nonpermissive temperature. Bcl-2 acted downstream of the accumulation of short-lived or aberrant proteins because it did not prevent the overexpression of the short-lived proteins p53, p27(kip1), and cyclins D1 and B1 under conditions of decreased ubiquitination. These results suggest the existence of short-lived proteins that may serve the role of caspase-independent effectors of apoptosis and attractive targets of the death-protective action of Bcl-2.

Role of an acidic compartment in tumor-necrosis-factor-alpha-induced production of ceramide, activation of caspase-3 and apoptosis.

Tumor necrosis factor-alpha (TNF-alpha) apoptosis by recruiting a complex of cytosolic proteins at its plasma membrane receptor. Among them is caspase-8, an interleukin-1beta-converting enzyme (ICE)-like protease that initiates an amplified protease cascade to activate the cell-death machinery. The latter comprises at least caspase-3 and caspase-7, which execute cell death by cleaving numerous protein substrates, including poly(ADP-ribose) polymerase. In addition, TNF-alpha stimulates the production of ceramide, which also activates the death machinery. Whether the signaling pathways elicited by caspase-8 and ceramide proceed independently or intersect at a specific subcellular site is unknown. Using the lysosomotropic agent NH4Cl and the vesicularization inhibitor brefeldin A, we show here the convergence of TNF-alpha-induced death signaling on an acidic, subcellular compartment reminiscent of lysosomes. This compartment generates at least two signaling pathways that account for the caspase-3 activation and apoptosis induced by TNF-alpha, one involving ceramide and caspase-unrelated adapter molecules and another involving yet unknown lysosomal mediators. The apoptosis inhibitor Bcl-2 specifically acts on the ceramide-activated pathway to block caspase-3 activation and apoptosis. The latter result explains why Bcl-2 only partially blocks TNF-alpha-induced apoptosis.

Bcl-2 does not require Raf kinase activity for its death-protective function.

It has been widely accepted that the oncogene product bcl-2 protects mammalian cells from programmed cell death (apoptosis). The molecules and signalling pathways upon which bcl-2 acts are, however, still ill-defined. Recently, bcl-2 was shown to interact with c-raf-1 in vitro. Furthermore, an active form of c-raf-1 delayed apoptosis induced by trophic factor deprivation and enhanced the death-suppressive function of bcl-2 when co-expressed. This has led to the hypothesis that bcl-2 communicates cell-death protection via a raf-dependent signal transduction pathway. Here we show, by various immunological and biochemical methods, that bcl-2 does not stably associate with c-raf-1 in cellular extracts prepared from fibroblasts before or after treatment with agents that induce apoptosis. Unexpectedly, bcl-2 function is entirely maintained, if not improved, when raf-dependent signalling is experimentally abrogated. In fact, bcl-2 allows the stable overexpression of a kinase-defective dominant-negative raf mutant that usually interferes with cell viability and/or proliferation. Our results indicate that bcl-2 does not require c-raf-1 kinase activity and an associated mitogen-activated protein kinase signalling pathway for its survival function. This property may be exploited to dissect cellular events that are dependent or independent of c-raf-1 kinase activity.

Coculture of rat embryonic proprioceptive sensory neurons and myotubes.

With the aim to study the cellular mechanism underlying the process of muscle spindle regeneration, dorsal root ganglia (DRG) neurons derived from 16-day rat embryos were cocultured with developing myotubes in a compartmentalized culture device. To accomplish the selective survival and neurite formation of the proprioceptive subpopulation, the neurotrophic factor, neurotrophin-3, was added to the culture medium. It appeared that the proprioceptive DRG neurons could develop specialized, Ia afferent terminal-like contacts with myotubes. However, these interactions were scarce and did not result in the induction of differentiation of the contacted myotubes into intrafusal fibers as normally occurs during in vivo development. The present coculture setup apparently lacks appropriate regulatory factors essential for the proper matching of sensory axons and intrafusal fiber precursors and the induction of a functional sensory myoneural connection.

Bcl-2 overexpression blocks activation of the death protease CPP32/Yama/apopain.

The C. elegans gene product ced-9 inhibits programmed cell death by negatively regulating the death-mediating protease ced-3. The mammalian homolog of ced-9 is the oncoprotein Bcl-2. Overexpression of Bcl-2 spares mammalian and nematodal cells from dying and prevents ectopic cell death in ced-9 loss-of-function mutants. Although Bcl-2 has been shown to act as an antioxidant under certain conditions, additional functions have emerged from studies under low oxygen pressure. Here we show that Bcl-2 overexpression impairs activation of the interleukin-1beta converting enzyme-related death protease CPP32/Yama/apopain, the mammalian homolog of ced-3. When U937 monocytes undergo programmed cell death in response to tumor necrosis factor alpha, the inactive CPP32 precursor is cleaved into its active forms. As a consequence poly(ADP ribose) polymerase, a major substrate of CPP32, is faithfully cleaved into a 85 kD fragment. Bcl-2 overexpressing cells are protected from tumor necrosis factor alpha-induced death and display neither CPP32 maturation nor PARP cleavage. The inhibitory effect of Bcl-2 on CPP32 activation is indirect since no physical interaction between the two proteins could be detected. These results indicate that Bcl-2 neutralizes an unknown cellular activator of CPP32 to save cells from programmed cell death.

Expression of calcium-binding proteins in the neurotrophin-3-dependent subpopulation of rat embryonic dorsal root ganglion cells in culture.

In this study we have examined the calcium-binding protein expression in rat embryonic (E16) dorsal root ganglia (DRG) neurons in vitro in the presence of neurotrophin-3 (NT-3). A comparison was made with the expression of calcium-binding proteins in DRG subpopulations that depended in vitro on nerve growth factor (NGF) or brain-derived neurotrophic factor (BDNF). Our results show that NT-3 promotes the survival of a DRG subpopulation of which over 75% expresses parvalbumin (PV). The majority of these PV-positive NT-3-dependent DRG neurons were large 'type A' neurons. Expression of calbindin-D28k (CaBP) and calretinin (Calr) in the NT-3-dependent DRG population was seen in smaller fractions (between 12 and 17%) of the surviving DRG neurons and in both type A and B neurons. The preferential expression of PV in NT-3-dependent type A neurons is unique in comparison to the expression of PV and the other calcium-binding proteins in DRG neurons surviving in vitro in the presence of NGF or BDNF.