Single-nucleus transcriptomics reveals a gatekeeper role for FOXP1 in primate cardiac aging

Aging poses a major risk factor for cardiovascular diseases, the leading cause of death in the aged population. However, the cell type-specific changes underlying cardiac aging are far from being clear. Here, we performed single-nucleus RNA-sequencing analysis of left ventricles from young and aged cynomolgus monkeys to define cell composition changes and transcriptomic alterations across different cell types associated with age. We found that aged cardiomyocytes underwent a dramatic loss in cell numbers and profound fluctuations in transcriptional profiles. Via transcription regulatory network analysis, we identified FOXP1, a core transcription factor in organ development, as a key downregulated factor in aged cardiomyocytes, concomitant with the dysregulation of FOXP1 target genes associated with heart function and cardiac diseases. Consistently, the deficiency of FOXP1 led to hypertrophic and senescent phenotypes in human embryonic stem cell-derived cardiomyocytes. Altogether, our findings depict the cellular and molecular landscape of ventricular aging at the single-cell resolution, and identify drivers for primate cardiac aging and potential targets for intervention against cardiac aging and associated diseases.

Single-nucleus profiling unveils a geroprotective role of the FOXO3 in primate skeletal muscle aging

Age-dependent loss of skeletal muscle mass and function is a feature of sarcopenia, and increases the risk of many aging-related metabolic diseases. Here, we report phenotypic and single-nucleus transcriptomic analyses of non-human primate skeletal muscle aging. A higher transcriptional fluctuation was observed in myonuclei relative to other interstitial cell types, indicating a higher susceptibility of skeletal muscle fiber to aging. We found a downregulation of FOXO3 in aged primate skeletal muscle, and identified FOXO3 as a hub transcription factor maintaining skeletal muscle homeostasis. Through the establishment of a complementary experimental pipeline based on a human pluripotent stem cell-derived myotube model, we revealed that silence of FOXO3 accelerates human myotube senescence, whereas genetic activation of endogenous FOXO3 alleviates human myotube aging. Altogether, based on a combination of monkey skeletal muscle and human myotube aging research models, we unraveled the pivotal role of the FOXO3 in safeguarding primate skeletal muscle from aging, providing a comprehensive resource for the development of clinical diagnosis and targeted therapeutic interventions against human skeletal muscle aging and the onset of sarcopenia along with aging-related disorders.

Neural Correlates of Spatial Navigation in Primate Hippocampus / 神经科学通报·英文版

The hippocampus has been extensively implicated in spatial navigation in rodents and more recently in bats. Numerous studies have revealed that various kinds of spatial information are encoded across hippocampal regions. In contrast, investigations of spatial behavioral correlates in the primate hippocampus are scarce and have been mostly limited to head-restrained subjects during virtual navigation. However, recent advances made in freely-moving primates suggest marked differences in spatial representations from rodents, albeit some similarities. Here, we review empirical studies examining the neural correlates of spatial navigation in the primate (including human) hippocampus at the levels of local field potentials and single units. The lower frequency theta oscillations are often intermittent. Single neuron responses are highly mixed and task-dependent. We also discuss neuronal selectivity in the eye and head coordinates. Finally, we propose that future studies should focus on investigating both intrinsic and extrinsic population activity and examining spatial coding properties in large-scale hippocampal-neocortical networks across tasks.

Aneurisma aórtico torácico com trombose associada em Bugio-preto (Alouatta caraya) / Thoracic aortic aneurysm with associated thrombosis in black-and-gold howler monkey (Alouatta caraya)

O aneurisma é uma dilatação anormal e permanente das artérias, resultante do enfraquecimento da parede do vaso adelgaçamento da camada média e enfraquecimento da camada elástica. Em animais, a maioria dos casos de aneurisma tem origem idiopática e são detectados acidentalmente durante a necropsia. O objetivo deste trabalho é relatar um caso de aneurisma aórtico com trombose associada em Bugio-preto(Alouatta caraya), bem como seus aspectos patológicos. O animal era adulto, macho, pertencente ao Centro Nacional de Primatas (CENP), na cidade de Ananindeua-PA, foi encaminhado para exame necroscópico para investigação da causa mortis. No histórico do animal, não constava qualquer enfermidade. O animal apresentava bom escore de condição corporal com preservação da topografia anatômica dos órgãos. Entretanto, observou-se presença de aumento de volume localizado em aorta torácica, a 1,4 cm da base do coração. Na abertura aórtica foi observado dilatações de tamanhos variados e, no interior da maior dilatação, notou-se uma estrutura de coloração vermelho escuro, aderida, de aspecto seco e superfície áspera, medindo 1,5 cm. Aneurismas aórticos em primatas não humanos não são comuns, porém já foram reportados na literatura. O diagnóstico precoce utilizando exames complementares é importante, porém, ainda há recursos não empregados na rotina veterinária tornando ainda mais difícil o diagnóstico e prevenção. Por isso, na medicina veterinária, os aneurismas são detectados acidentalmente durante a necropsia. Com base nos achados anatomopatológicos, concluiu-se que o animal veio a óbito por trombose associada a aneurisma aórtico.

An aneurysm is an abnormal and permanent dilation of the arteries, resulting from the weakening of the vessel wall.thinning of the middle layer and weakening of the elastic layer. In animals, most cases of aneurysm are idiopathic. This paper aimed to report a case of aortic aneurysm with associated thrombosis in a black-and-gold howler monkey(Alouatta caraya), as well as its pathological aspects. The animal was an adult, male, belonging to the National Primate Center (CENP), in the city of Ananindeua-PA, that was referred for necroscopic examination to investigate the causa mortis. In the animal's history, there was no disease. The animal had a good body condition score with preservation of the anatomical topography of the organs. However, there was an increase in volume located in the thoracic aorta, 1.4 cm from the base of the heart. In the aortic opening, dilations of different sizes were observed, and inside the largest dilatation, a structure of dark red color, adhered, with a dry appearance and rough surface, measuring 1.5 cm was noted in addition to dilations of different sizes. Inside the largest cavitation, a dark red structure was observed, adhered, with a dry appearance and rough surface, measuring 1.5 cm. Aortic aneurysms in non-human primates are incommon, but have been reported in the literature. Early diagnosis using complementary exams is important, however, there are still resources not used in the veterinary routine, making diagnosis and prevention even more difficult. Therefore, in veterinary medicine, aneurysms are accidentally detected during necropsy. Based on the anatomopathological findings, it was concluded that the animal died due to thrombosis associated with an aortic aneurysm.

Facial restoration after trauma - nasolabial in monkey bugio - Alouatta caraya (Humboldt, 1812) - first case report / [Restauração facial pós trauma nasolabial em macaco bugio - Alouatta caraya (Humboldt, 1812) - relato de caso]

In the last decades in the State of Mato Grosso do Sul - Brazil, the reduction in the preservation of areas due to the degradation of the biome and destruction of the natural environment has caused animals, mainly in the order of non-human primates, to come closer to towns and highways, increasing the number of accidents and in some cases, deaths. New surgical techniques have been developed that favor these species as explained in this report. The howler monkey patient was traumatized in the facial region damaging important vital structures such as facial muscle groups responsible for swallowing food, chewing, breathing, defense, and communication (vocalization and mimicry), in addition to the cartilaginous nasal structures. However, reconstructive facial surgical techniques, used on humans, showed satisfactory results from an anatomical, functional, and aesthetic point of view in howler monkey, with acceptance of the animal with a safe postoperative period for a full recovery of the primate patient.(AU)

Nas últimas décadas, no estado do Mato Grosso do Sul - Brasil, a redução de áreas preservadas pela degradação de biomas e pela destruição de habitat naturais tem favorecido a aproximação de animais - muitos desses, primatas não humanos - em cidades e rodovias, aumentando o número de acidentes e, em alguns casos, de mortes. Novas técnicas cirúrgicas têm sido desenvolvidas, favorecendo essas espécies, como reportado neste trabalho. O paciente macaco bugio foi traumatizado em região facial, envolvendo importantes estruturas vitais, como grupos musculares faciais responsáveis pela apreensão alimentar, mastigação, respiração, defesa e comunicação (vocalização e mímicas), além das estruturas cartilaginosas nasais. No entanto, técnicas cirúrgicas reconstrutivas em face aplicadas e descritas em humanos apresentaram resultados satisfatórios dos pontos de vista anatômico, fisiológico e visual nos macacos bugio, com aceitação deles diante do estresse, com pós-operatório seguro, resultando na reabilitação do paciente primata.(AU)

TRYPANOSOMA spp. in captive primates in a brazilian zoo

Captive animals, despite the constant care provided, are susceptible to infections from different sources. We herein report the natural trypanosome infection of 11 (28.2% positive) out of 39 non-human primates from 13 different species, in a Brazilian zoological park. Immunofluorescent antibody test (IFAT) and conventional polymerase chain reaction (cPCR) ruled out Trypanosoma cruzi, the etiological agent of Chagas disease. However, sequencing performed with positive samples employing hsp70 primers revealed similarities from 86% to 88% to diverse trypanosomes, including T. cruzi, Trypanosoma grayi, Trypanosoma lewisi, Trypanosoma rangeli and Trypanosoma vivax. We believe that the low similarity values obtained by sequencing reflect the difficulties in the molecular identification of trypanosomes, which share a large portion of their genetic material; this similarity may also preclude the diagnosis of co-infection by more than one trypanosome species. Thus, our study demonstrates the presence of diverse trypanosomes in primates, which are susceptible to infection by these parasites. Mechanical devices such as windows and bed nets, etc., are required to avoid vector insects in these environments, in addition to preventive quarantining of animals recently introduced into zoos. Therefore, investigation of the parasites in both the animals already residing in the zoo and those being introduced is of paramount importance, although no easy task.

Frecuencia de enteroparásitos en primates Cebidae y Callitrichidae del Zoológico de Cali, Colombia: implicaciones zoonóticas / Frequency of enteroparasites in Cebidae and Callitrichidae primates at the Zoológico de Cali, Colombia: Zoonotic implications

Resumen | Introducción. Los enteroparásitos pueden generar problemas en animales bajo cuidado humano en zoológicos y centros de acogida. Los animales silvestres presentan bajas cargas parasitarias, pero estas pueden ser mayores y llevar a manifestaciones clínicas cuando se trata de animales resguardados en recintos, lo que aumenta los gastos en tratamientos y cuidados médicos. Por otro lado, algunos enteroparásitos pueden causar infecciones zoonóticas en los cuidadores, los visitantes y otros animales del zoológico, así como afectar los programas de recuperación de especies amenazadas de extinción. Objetivos. Determinar la presencia y prevalencia de enteroparásitos con potencial de transmisión zoonótica en primates de las familias Cebidae y Callitrichidae del Zoológico de Cali, entre septiembre y noviembre de 2017. Materiales y métodos. Se hizo un estudio transversal prospectivo, para lo cual se recolectaron muestras seriadas de 50 individuos pertenecientes a siete especies de dos familias de primates y se analizaron mediante examen coprológico, flotación y coloración Kinyoun, entre septiembre y noviembre de 2017. Resultados. Según su prevalencia, los géneros de parásitos hallados en las siete especies de primates evaluadas, fueron Blastocystis spp., Trichomonas spp., Giardia spp., Entamoeba spp., Strongyloides spp., Cyclospora sp. y Trichuris sp. Conclusiones. Por lo menos, seis de los géneros de parásitos identificados tienen implicaciones zoonóticas, lo cual hace necesario establecer las posibles vías de infección de los primates del Zoológico de Cali e implementar protocolos de manejo que reduzcan el riesgo de transmisión a los humanos y a otros animales de la colección. Además, se presenta la información relevante sobre el potencial zoonótico de los enteroparásitos hallados.

Abstract | Introduction: Enteroparasites can cause problems in animals kept under human care in zoos and shelters. Wild animals have low parasitic loads but when sheltered in closed places they can be higher and lead to clinical manifestations, which increases the cost of medical treatments and care. On the other hand, some enteroparasites can represent a potential risk of zoonotic infection for their animal keepers, visitors, and other zoo animals. In addition, they could affect recovery programs for endangered species. Objectives: To establish the presence and prevalence of potentially zoonotic enteroparasites in primates of the Cebidae and Callitrichidae families at the Zoológico de Cali from September to November, 2017. Materials and methods: We conducted a prospective cross-sectional study. Serial samples from 50 individuals belonging to seven species and two primate families were analyzed by ova and parasite test, flotation, and Kinyoun stain between September and November, 2017. Results: In order of frequency, the parasite genera found in the seven primate species evaluated were Blastocystis spp.,Trichomonas spp., Giardia spp., Entamoeba spp., Strongyloides spp., Cyclospora sp., and Trichuris sp. Conclusions: At least six of the parasite genera found have potential zoonotic implications. It is necessary to establish what are the infection sources at the Zoológico de Cali and implement management protocols to reduce the risk of transmission to both humans and other animals in the collection. Additionally, we offer relevant information on the zoonotic potential of each of the enteroparasites found.

Molecular detection of trypanosomatids in neotropical primates in the state of Mato Grosso, Midwest, Brazil / Detecção molecular de tripanossomatídeos em primatas neotropicais no estado de Mato Grosso, Centro-Oeste, Brasil

Abstract Trypanosomatids are uniflagellate protozoa belonging to the Trypanosomatidae family. The genera Trypanosoma and Leishmania are of paramount importance as they contain species that cause serious diseases, such as Chagas disease and Leishmaniasis, respectively. The objective of the present study was to identify trypanosomatids present in the whole blood of free-living and captive neotropical primates in Mato Grosso State, Midwest Brazil. Between 2017 and 2019, 38 blood samples were collected from seven different neotropical primate species in seven cities in the state. Through molecular techniques, including polymerase chain reaction (PCR) to amplify a fragment of the kinetoplast DNA (kDNA) and 18S ribosomal RNA (18S rRNA) gene, sequencing, and phylogenetic analysis, nine Leishmania spp. [seven L. infantum and two L. (Leishmania) amazonensis] and two Trypanosoma spp. (T. minasense and T. rangeli) were identified. This study contributes to understanding the occurrence and epidemiology of trypanosomatids in Mato Grosso State and the importance of neotropical primates as trypanosome hosts and possible infection sources for other animals and humans. Future identification of other blood pathogens in neotropical primates will assist in disease control and prevention strategies.

Resumo Tripanossomatídeos são protozoários uniflagelados pertencentes à família Trypanosomatidae. Os gêneros Trypanosoma e Leishmania são de suma importância por conterem espécies causadoras de doenças graves, como doença de Chagas e Leishmaniose, respectivamente. O objetivo do presente estudo foi identificar tripanossomatídeos presentes no sangue total de primatas neotropicais de vida livre e cativos no Estado de Mato Grosso, Centro-Oeste do Brasil. Entre 2017 e 2019, foram coletadas 38 amostras de sangue de sete diferentes espécies de primatas neotropicais em sete cidades do Estado. Foram identificados por meio de técnicas moleculares, incluindo reação em cadeia da polimerase (PCR), para amplificar um fragmento do DNA do cinetoplasto (kDNA) e do gene do RNA ribossômico 18S (rRNA 18S), sequenciamento e análise filogenética, nove Leishmania spp. [sete L. infantum e dois L. (Leishmania) amazonensis] e dois Trypanosoma spp. (T. minasense e T. rangeli). Este estudo contribui para o entendimento da ocorrência e epidemiologia dos tripanossomatídeos no Estado de Mato Grosso e a importância dos primatas neotropicais como hospedeiros tripanossômicos e possíveis fontes de infecção para outros animais e humanos. A identificação futura de outros patógenos do sangue em primatas neotropicais ajudará no controle de doenças e em estratégias de prevenção.

Prevalência e distribuição espacial da ocorrência de helmintos em primatas não humanos de vida livre no estado do Rio de Janeiro, Brasil / [Prevalence and spatial distribution of the occurrence of helminths in free-living nonhuman primates in the State of Rio de Janeiro, Brazil]

Seiscentos primatas neotropicais foram submetidos a exames post mortem para avaliação da prevalência parasitária de helmintos gastrointestinais. Foram examinados 556 calitriquídeos (Callithrix spp.), 23 bugios (Alouatta guariba), 19 macacos-pregos (Sapajus nigritus), um mico-leão-dourado (Leontopithecus rosalia) e um mico-leão-da-cara-dourada (Leontopithecus chrysomelas). Do total de 600 animais, foram encontrados espécimes parasitos pertencentes aos filos Acanthocephala, Nemathelmintes e Platyhelminthes (classes Trematoda e Cestoda) em 110 primatas. A prevalência de primatas positivos para, pelo menos, uma espécie de helminto foi de 18,3% (110/600), sendo destes 83,6% (92/110) calitriquídeos, 8,2% (9/110) bugios, 6,4% (7/110) macacos-pregos, 0,9% (1/110) mico-leão-dourado e 0,9% (1/110) mico-leão-da-cara dourada. Em 80,4% (74/92) dos calitriquídeos foram encontrados nematoides Primasubulura sp. e em 1,1% (1/92) nematoides Trypanoxyuris callithrix, em 26,1% (24/92) acantocéfalos (Pachysentis sp.) e em 5,4% (5/92) digenéticos (Platynosomum sp.); em 77,8% (7/9) dos bugios foram encontrados nematoides (Trypanoxyuris minutus), em 11,1% (1/9) acantocéfalos (Pachysentis sp.) e em 11,1% (1/9) cestoides (Bertiella sp.); em 14,3% (1/7) dos macacos-pregos foram encontrados nematoides (Physaloptera sp.), em 28,6% (2/7) acantocéfalos (Prostenorchis sp.) e em 14,3% (1/7) digenéticos (Platynosomum sp.) e no mico-leão-da-cara-dourada foram encontrados acantocéfalos (Prostenorchis sp.). Foi realizado o georreferenciamento dos pontos de encontro dos cadáveres para pontuar a distribuição dos helmintos por região.(AU)

Six hundred neotropical primates underwent postmortem examinations to evaluate the parasitic prevalence of gastrointestinal helminths. Fifty-five callitrichids tamarins (Callithrix spp.), 23 howlers (Alouatta guariba), 19 nail monkeys (Sapajus nigritus), a golden lion tamarin (Leontopithecus rosalia) and a golden-faced lion tamarin (Leontopithecus chrysomelas) were examined. Parasitic specimens belonging to phylums Acantocephala, Nemathelmintes and Platyhelmintes (Trematoda and Cestoda Classes) were found. The prevalence of primates positive for at least one species of helminth was 18.3% (110/600), of which 83.6% (92/110) callitrichids, 8.2% (9/110) howler monkeys, 6.4% (7/110) capuchin monkeys, 0.9% (1/110) golden lion tamarin and 0.9% (1/110) golden faced lion tamarin. In 80.4% (74/92) of callitrichids nematodes (Primasubulura sp.) were found, and in 1.1% (1/92) nematodes (Trypanoxyuris callithricis), in 26.1% (24/92) acanthocephalus (Pachysentis sp.) and 5.4% (5/92) digenetics (Platynosomum sp.); in 77.8% (7/9) of howler monkeys presented nematodes (Trypanoxyuris minutus), 11.1% (1/9) acanthocephalus (Pachysentis sp.) and 11.1% (1/9) cestoids (Bertiella sp.); in 14.3% (1/7) of capuchin monkeys presented nematodes (Physaloptera sp.), 28.6% (2/7) acanthocephalus (Prostenorchis sp.) and 14.3% (1/7) digenetics (Platynosomum sp.) and in the golden-faced lion tamarin acanthocephalus (Prostenorchis sp.) were found. Georreferencing of the meeting points of the cadavers was performed in order to punctuate the distribution of helminths by region.(AU)

Habitat use, fruit consumption, and population density of the black-headed night monkey, Aotus nigriceps, in southeastern Peru

The black-headed night monkey, Aotus nigriceps, has one of the largest distribution ranges of the 11 night monkey species found across Central and South America. Yet, only three studies have focused on their ecology, describing considerable variation in habitat, group composition, and population density. Therefore, we analyzed habitat use, group composition, population density, and diet of 14 groups at two field sites in southeastern Peru. All sampled groups were found in secondary tropical rainforest, often dominated by native bamboo species. Half of the observed sleeping sites were in bamboo stands, though groups also emerged from cane thickets and lianas. This contrasts with other Aotus studies which have found groups living in tree cavities and lianas. Population density estimates for both sites were 19 and 50 individuals per km2, outside the range previously reported for A. nigriceps (31−34 individuals per km2). We recovered seeds of 12 species from fecal samples over the course of two field seasons, belonging mainly to Cecropiaceae, Piperaceae and Moraceae. Our results suggest that the black-headed night monkey in Peru can survive and even thrive in secondary forest, feeding extensively on pioneer species, occupying a range of forest types, all while living near human settlements. (AU)

Yellow fever surveillance challenge: Investigation of a marmoset non-autochthonous case

Yellow fever (YF) surveillance in Brazil is focused mainly on the detection of epizootic events regarding New World non-human primates (NWNHP). We present a challenging case of a Callitrichidae (Callithrix spp) kept as a domiciliated pet that lived in the urban area of São Paulo municipality and was positive to YF virus by RT-qPCR and immunohistochemistry. After investigation, it was the first occurrence of non-autochthonous YF case of NWNHP described, with probable place of infection in the North shore of São Paulo state. This case illustrates the importance of coordinated laboratorial and field actions, and risks posed by transit of wildlife.

Fragment shape and size, landscape permeability and fragmentation level as predictors of primate occupancy in a region of Brazilian Cerrado

Human activities result in the formation of a mosaic of forest patches within a non-habitat matrix. The response of the local biodiversity to changes in land-use may occur at different scales. It is important to evaluate the effects of the attributes of both the patches and the surrounding landscape on the occupancy of forest patches by animal populations. Here, we assessed the predictive potential of local (basal area, tree density), patch (size, shape) and landscape scale (total area of forest, number of patches, matrix permeability, patch proximity) variables on the occupancy of forest patches by the syntopic primates Alouatta caraya, Sapajus libidinosus and Callithrix penicillata in the city of Goiânia in the Cerrado region of central Brazil. We used playback to survey primate populations in 22 focal patches and assessed the landscape within a 1000 m buffer zone around each site. In A. caraya, occupancy was influenced by the shape of the focal patches, the amount of forest and fragmentation level of the landscape. Focal patch size and the permeability of the matrix were the principal determinants of the occupancy of S. libidinosus. None of the predictors influenced patch occupancy in C. penicillata, and the structure of the vegetation did not influence occupancy in any of the species. The preservation of as many forest patches as possible, both large and small, as well as gallery forests, and the enhancement of matrix permeability will be essential for the long-term conservation of the syntopic primates of the Cerrado of central Brazil.

Stimulus and reward information encoded by population neurons in the primate prefrontal cortex and striatum / 生理学报

It has been reported that single-unit activity in the prefrontal cortex (PFC) and striatum represented visual stimulus and reward information. But how to encode these pieces of information is quite complex from the view of single-neuron activity. Different neurons represented stimulus or reward information in different task epochs with increasing or decreasing their activities relative to their baseline firing rates. The present paper was aimed to study whether population neurons in the two brain areas could stably encode task-relevant parameters in a whole trial period. We recorded single-unit activities in the lateral PFC (LPFC) and striatum while the monkey was performing a stimulus- reward prediction task, and analyzed the neuronal activities by the method of a multi-variable regression model and the linear support vector machine. The results showed that, although proportions of task-related neurons in the two areas varied largely in the whole trial period, LPFC population neurons encoded reward and stimulus information stably and reliably. Population neurons in the striatum encoded only reward information, not stimulus information. A group of neurons in the two areas represented combined information of stimulus and reward. Further analysis showed that LPFC neurons encoded reward information for a group of relevant stimuli, while striatal neurons encoded reward information for a specific stimulus. These results suggest that both LPFC and striatal population neurons are able to stably represent task-relevant information, but from different aspects of the task. The different strategies to encode information in the LPFC and striatum suggest their different contributions in reward-based decision making.

Predation of Boana boans (Anura, Hylidae) by an opportunistic frugivorous primate

Although relatively common among omnivorous primates, anurophagy is still poorly documented in frugivorous species. Here we report the predation of a giant gladiator treefrog (Boana boans) by a large arboreal frugivore, the gray woolly monkey (Lagothrix lagotricha cana). The predation event occurred in a stretch of riparian forest located in a fragmented region in Cacoal, Rondônia state, in southwestern Brazilian Amazonia. Anurans can be a profitable, non-contested, and relatively easily acquired alternative resource for gray woolly monkeys, helping to fulfill their demand for protein, especially in periods of fruit scarcity. This new record broadens the knowledge on the natural history and predators of the giant gladiator frog. (AU)

Acute effects of ayahuasca in a juvenile non-human primate model of depression

Objective: The incidence rate of major depression in adolescents reaches approximately 14%. This disorder is usually recurrent, without remission of symptoms even after pharmacological treatment, and persists throughout adult life. Since the effects of antidepressants take approximately 2 weeks to begin, new pharmacological therapies are under continuous exploration. Recent evidence suggests that psychedelics could produce rapid antidepressant effects. In this study, we evaluated the potential antidepressant effects of ayahuasca in a juvenile non-human primate model of depression. Methods: While living with their families, juvenile marmosets (8 males; 7 females) were observed on alternate days for four weeks during a baseline phase. This was followed by 8 weeks of an induced depressive state protocol, the social isolated context (IC), in which the animals were monitored in the first and last weeks. Subsequently, five males and four females were randomly selected for treatment, first with a single administration of saline vehicle (1.67 mL/300 g of body weight, via gavage), followed by a single dose of ayahuasca (1.67 mL/300 g of body weight, via gavage). Both phases lasted 1 week and the animals were monitored daily. A third week of sampling was called the tardive-pharmacological effects phase. In all phases the marmosets were assessed for behavior, fecal cortisol levels, and body weight. Results: After IC, the animals presented typical hypocortisolemia, but cortisol recovered to baseline levels 24 h after an acute dose of ayahuasca; this recovery was not observed in vehicle-treated animals. Additionally, in males, ayahuasca, but not the vehicle, reduced scratching, a stereotypic behavior, and increased feeding. Ayahuasca treatment also improved body weight to baseline levels in both sexes. The ayahuasca-induced behavioral response had long-term effects (14 days). Thus, in this translational juvenile animal model of depression, ayahuasca presented beneficial effects. Conclusions: These results can contribute to the validation of ayahuasca as an antidepressant drug and encourage new studies on psychedelic drugs as a tool for treating mood disorders, including for adolescents with early-onset depression.

Efficient Production of Murine Uterine Damage Model

BACKGROUND: Thin or damaged endometrium causes uterine factor-derived infertility resulting in a failure of embryonic implantation. Regeneration of endometrium is a major issue in gynecology and reproductive medicine. Various types of cells and scaffolds were studied to establish an effective therapeutic strategy. For this type of investigations, production of optimal animal models is indispensable. In this study, we tried to establish various murine uterine damage models and compared their features. METHODS: Three to ten-week-old C57BL/6 female mice were anesthetized using isoflurane. Chemical and mechanical methods using ethanol (EtOH) at 70 or 100% and copper scraper were compared to determine the most efficient condition. Damage of uterine tissue was induced either by vaginal or dorsal surgical approach. After 7-10 days, gross and microscopic morphology, safety and efficiency were compared among the groups. RESULTS: Both chemical and mechanical methods resulted in thinner endometrium and reduced number of glands. Gross morphology assessment revealed that the damaged regions of uteri showed various shapes including shrinkage or cystic dilatation of uterine horns. The duration of anesthesia significantly affected recovery after procedure. Uterine damage was most effectively induced by dorsal approach using 100% EtOH treatment compared to mechanical methods. CONCLUSION: Taken together, murine uterine damage models were most successfully established by chemical treatment. This production protocols could be applied further to larger animals such as non-human primate.

Rise of the Visible Monkey: Sectioned Images of Rhesus Monkey

BACKGROUND: Gross anatomy and sectional anatomy of a monkey should be known by students and researchers of veterinary medicine and medical research. However, materials to learn the anatomy of a monkey are scarce. Thus, the objective of this study was to produce a Visible Monkey data set containing cross sectional images, computed tomographs (CTs), and magnetic resonance images (MRIs) of a monkey whole body. METHODS: Before and after sacrifice, a female rhesus monkey was used for 3 Tesla MRI and CT scanning. The monkey was frozen and sectioned at 0.05 mm intervals for the head region and at 0.5 mm intervals for the rest of the body using a cryomacrotome. Each sectioned surface was photographed using a digital camera to obtain horizontal sectioned images. Segmentation of sectioned images was performed to elaborate three-dimensional (3D) models of the skin and brain. RESULTS: A total of 1,612 horizontal sectioned images of the head and 1,355 images of the remaining region were obtained. The small pixel size (0.024 mm × 0.024 mm) and real color (48 bits color) of these images enabled observations of minute structures. CONCLUSION: Due to small intervals of these images, continuous structures could be traced completely. Moreover, 3D models of the skin and brain could be used for virtual dissections. Sectioned images of this study will enhance the understanding of monkey anatomy and foster further studies. These images will be provided to any requesting researcher free of charge.

Increased CD68/TGFβ Co-expressing Microglia/Macrophages after Transient Middle Cerebral Artery Occlusion in Rhesus Monkeys

The function of microglia/macrophages after ischemic stroke is poorly understood. This study examines the role of microglia/macrophages in the focal infarct area after transient middle cerebral artery occlusion (MCAO) in rhesus monkeys. We measured infarct volume and neurological function by magnetic resonance imaging (MRI) and non-human primate stroke scale (NHPSS), respectively, to assess temporal changes following MCAO. Activated phagocytic microglia/macrophages were examined by immunohistochemistry in post-mortem brains (n=6 MCAO, n=2 controls) at 3 and 24 hours (acute stage), 2 and 4 weeks (subacute stage), and 4, and 20 months (chronic stage) following MCAO. We found that the infarct volume progressively decreased between 1 and 4 weeks following MCAO, in parallel with the neurological recovery. Greater presence of cluster of differentiation 68 (CD68)-expressing microglia/macrophages was detected in the infarct lesion in the subacute and chronic stage, compared to the acute stage. Surprisingly, 98~99% of transforming growth factor beta (TGFβ) was found colocalized with CD68-expressing cells. CD68-expressing microglia/macrophages, rather than CD206⁺ cells, may exert anti-inflammatory effects by secreting TGFβ after the subacute stage of ischemic stroke. CD68⁺ microglia/macrophages can therefore be used as a potential therapeutic target.

Abnormal Mitochondria in a Non-human Primate Model of MPTP-induced Parkinson's Disease: Drp1 and CDK5/p25 Signaling

Mitochondria continuously fuse and divide to maintain homeostasis. An impairment in the balance between the fusion and fission processes can trigger mitochondrial dysfunction. Accumulating evidence suggests that mitochondrial dysfunction is related to neurodegenerative diseases such as Parkinson's disease (PD), with excessive mitochondrial fission in dopaminergic neurons being one of the pathological mechanisms of PD. Here, we investigated the balance between mitochondrial fusion and fission in the substantia nigra of a non-human primate model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD. We found that MPTP induced shorter and abnormally distributed mitochondria. This phenomenon was accompanied by the activation of dynamin-related protein 1 (Drp1), a mitochondrial fission protein, through increased phosphorylation at S616. Thereafter, we assessed for activation of the components of the cyclin-dependent kinase 5 (CDK5) and extracellular signal-regulated kinase (ERK) signaling cascades, which are known regulators of Drp1(S616) phosphorylation. MPTP induced an increase in p25 and p35, which are required for CDK5 activation. Together, these findings suggest that the phosphorylation of Drp1(S616) by CDK5 is involved in mitochondrial fission in the substantia nigra of a non-human primate model of MPTP-induced PD.

Three-axis Modification of Coordinates Enables Accurate Stereotactic Targeting in Non-human Primate Brains of Different Sizes

The brain grows with age in non-human primates (NHPs). Therefore, atlas-based stereotactic coordinates cannot be used directly to target subcortical structures if the size of the animal's brain differs from that used in the stereotactic atlas. Furthermore, growth is non-uniform across different cortical regions, making it difficult to simply apply a single brain-expansion ratio. We determined the skull reference lines that best reflect changes in brain size along the X, Y, and Z axes and plotted the changes in reference-line length against the changes in body weight. The skull reference lines had a linear relationship with body weight. However, comparison of skull reference lines with body weight confirmed the non-uniform skull growth during postnatal development, with skull growth more prominent in the X and Y axes than the Z axis. Comparing the differences between the atlas-based lengths and those calculated empirically from plot-based linear fits, we created craniometric indices that can be used to modify stereotactic coordinates along all axes. We verified the accuracy of the corrected stereotactic targeting by infusing dye into internal capsule in euthanized and preserved NHP brains. Our axis-specific, craniometric-index-adjusted stereotactic targeting enabled us to correct for targeting errors arising from differences in brain size. Histological verification showed that the method was accurate to within 1 mm. Craniometric index-adjusted targeting is a simple and relatively accurate method that can be used for NHP stereotactic surgery in the general laboratory, without the need for high-resolution imaging.