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In humans, cognitive aging is highly variable, with some individuals experiencing decline while others remain stable, and different cognitive domains exhibiting uneven vulnerability to aging. The neural mechanisms driving this intra- and inter-individual variability are not fully understood, making longitudinal studies in translational models essential for elucidating the timelines and processes involved. The common marmoset (Callithrix jacchus), a short-lived nonhuman primate, offers an unprecedented opportunity to conduct longitudinal investigations of aging and age-related disease over a condensed time frame, in a highly translatable animal model. The potential of the marmoset as a model for cognitive aging is indisputable, but a comprehensive cognitive battery tailored for longitudinal aging studies has not yet been developed, applied, or validated. This represents a critical missing piece for evaluating the marmoset as a model and understanding the extent to which marmoset cognitive aging mirrors the patterns found in humans, including whether marmosets have individual variability in their vulnerability to age-related cognitive decline. To address this, we developed a comprehensive touchscreen-based neuropsychological test battery for marmosets (MarmoCog), targeting five cognitive domains: working memory, stimulus-reward association learning, cognitive flexibility, motor speed, and motivation. We tested a large cohort of marmosets, ranging from young adults to geriatrics, over several years. We found significant variability in cognitive aging, with the greatest decline occurring in domains dependent on the prefrontal cortex and hippocampus. Additionally, we observed significant inter-individual variability in vulnerability to age-related cognitive decline: some marmosets declined across multiple domains, others in just one, and some showed no decline at all. This pattern mirrors human cognitive aging, solidifies the marmoset as an advantageous model for age-related cognitive decline, and provides a strong foundation for identifying the neural mechanisms involved.

UNASSIGNED: Today, high-voltage (HV) lines create a pernicious environment for humans living or working in the vicinity and even under these lines. The male rhesus monkey is used to investigate the effects of fields produced by HV towers. This study examines the function and level of impact in rhesus monkeys\' brains from the cerebellum\'s cognitive, biological, and structural perspective.
UNASSIGNED: Two monkeys have been used, one as a control and the second as a test. The monkey under test was subjected to a simulated HV electrical field of 3 kV/m, 4 hours a day, for 1 month. Behavioral tests were performed using a device designed and built for this purpose. Concentration analysis of adrenocorticotropic hormones (ACTH) and inspection of glucocorticoid receptor gene\'s (GR) expression were performed by the reverse transcription polymerase chain reaction method. Changes in cerebellar anatomy were examined with magnetic resonance imaging (MRI). All tests were performed before and after the study period and compared with the control monkey.
UNASSIGNED: Cognitive tests showed a significant reduction for the monkey exposed to the HV electrical field in the first week after imposition compared with the same time before. Also, the expression of the GR gene decreased, and the concentration of ACTH hormone in plasma increased. Surveying the level of cerebral MRI images did not show any difference, but hemorrhage was evident in a part of the cerebellum.
UNASSIGNED: The tested monkey\'s cognitive, biological, and MRI results showed a decrease in visual learning and memory indices.

暂无摘要。

Maternal vaccinations administered prior to conception or during pregnancy enhance the immune protection of newborn infants against many pathogens. A feasibility experiment was conducted to determine if monkeys can be used to model the placental transfer of maternal antibody against SARS-CoV-2. Six adult rhesus monkeys were immunized with adjuvanted recombinant-protein antigens comprised of receptor-binding domain human IgG1-Fc fusion proteins (RBD-Fc) containing protein sequences from the ancestral-Wuhan or Gamma variants. The female monkeys mounted robust and sustained anti-SARS-CoV-2 antibody responses. Blood samples collected from their infants after delivery verified prenatal transfer of high levels of spike-specific IgG, which were positively correlated with maternal IgG titers at term. In addition, an in vitro test of ACE2 neutralization indicated that the infants\' IgG demonstrated antigen specificity, reflecting prior maternal immunization with either Wuhan or Gamma-variant antigens. All sera showed stronger ACE2-RBD binding inhibition when variants in the assay more closely resembled the vaccine RBD sequence than with more distantly related variants (i.e., Delta and Omicron). Monkeys are a valuable animal model for evaluating new vaccines that can promote maternal and infant health. Further, the findings highlight the enduring nature and safety of the immune protection elicited by an adjuvanted recombinant RBD-Fc vaccine.

Temporal discounting, in which the recipient of a reward perceives the value of that reward to decrease with delay in its receipt, is associated with impulsivity and psychiatric disorders such as depression. Here, we investigate the role of the serotonin 5-HT4 receptor (5-HT4R) in modulating temporal discounting in the macaque dorsal caudate nucleus (dCDh), the neurons of which have been shown to represent temporally discounted value. We first mapped the 5-HT4R distribution in macaque brains using positron emission tomography (PET) imaging and confirmed dense expression of 5-HT4R in the dCDh. We then examined the effects of a specific 5-HT4R antagonist infused into the dCDh. Blockade of 5-HT4R significantly increased error rates in a goal-directed delayed reward task, indicating an increase in the rate of temporal discounting. This increase was specific to the 5-HT4R blockade because saline controls showed no such effect. The results demonstrate that 5-HT4Rs in the dCDh are involved in reward-evaluation processes, particularly in the context of delay discounting, and suggest that serotonergic transmission via 5-HT4R may be a key component in the neural mechanisms underlying impulsive decisions, potentially contributing to depressive symptoms.

Papillomaviruses (PVs) are double-stranded, circular, epitheliotropic DNA viruses causing benign warts (papillomas) or inducing dysplasia that can progress to cancer. Although they have been identified in all vertebrate taxa, most classified types are human PVs (HPVs); relatively little is known about PVs in other species. Here we characterize a novel Gammapapillomavirus type, PtepPV1, from a nasal swab of a wild red colobus (Piliocolobus tephrosceles) in Kibale National Park, Uganda. The virus has a genome of 6576 bases, encoding the seven canonical early (E) ORFs (E6, E7, E1, E2, E4, E1^E4 and E8^E2) and two late (L) ORFs (L1 and L2) of the gammapapillomaviruses, and is 81.0% similar to HPV-mSK_118, detected in a cutaneous wart from an immunocompromised human patient, in the L1 gene at the amino acid level. Alphapapillomaviruses (genus Alphapapillomavirus) cause anogenital carcinomas such as cervical cancer and have been described previously in several nonhuman primates. However, the first gammapapillomavirus (genus Gammapapillomavirus), which cause transient cutaneous infections, was not described until 2019 in a healthy rhesus macaque (Macaca mulatta) genital swab. The new virus from red colobus, PtepPV1, has many genomic features encoded by high-risk oncogenic PVs, such as the E7 gene LXSXE and CXXC motifs, suggesting potential for pRb and zinc-finger binding, respectively. To our knowledge, PtepPV1 is also the first reported nonhuman primate PV found in the nasal cavity. PtepPV1 expands the known host range, geographical distribution, tissue tropism and biological characteristics of nonhuman primate PVs.

As humans age, some experience cognitive impairment while others do not. When impairment does occur, it is not expressed uniformly across cognitive domains and varies in severity across individuals. Translationally relevant model systems are critical for understanding the neurobiological drivers of this variability, which is essential to uncovering the mechanisms underlying the brain\'s susceptibility to the effects of aging. As such, non-human primates are particularly important due to shared behavioral, neuroanatomical, and age-related neuropathological features with humans. For many decades, macaque monkeys have served as the primary non-human primate model for studying the neurobiology of cognitive aging. More recently, the common marmoset has emerged as an advantageous model for this work due to its short lifespan that facilitates longitudinal studies. Despite their growing popularity as a model, whether marmosets exhibit patterns of age-related cognitive impairment comparable to those observed in macaques and humans remains unexplored. To address this major limitation for the development and evaluation of the marmoset as a model of cognitive aging, we directly compared working memory ability as a function of age in macaques and marmosets on the identical working memory task. Our results demonstrate that marmosets and macaques exhibit remarkably similar age-related working memory deficits, highlighting the value of the marmoset as a model for cognitive aging research within the neuroscience community.

Multiple cortical motor areas are critically involved in the voluntary control of discrete movement (e.g., reaching) and gait. Here, we outline experimental findings in nonhuman primates with clinical reports and research in humans that explain characteristic movement control mechanisms in the primary, supplementary, and presupplementary motor areas, as well as in the dorsal premotor area. We then focus on single-neuron activity recorded while monkeys performed motor sequences consisting of multiple discrete movements, and we consider how area-specific control mechanisms may contribute to the performance of complex movements. Following this, we explore the motor areas in cats that we have considered as analogs of those in primates based on similarities in their cortical surface topology, anatomic connections, microstimulation effects, and activity patterns. Emphasizing that discrete movement and gait modification entail similar control mechanisms, we argue that single-neuron activity in each area of the cat during gait modification is compatible with the function ascribed to the activity in the corresponding area in primates, recorded during the performance of discrete movements. The findings that demonstrate the premotor areas\' contribution to locomotion, currently unique to the cat model, should offer highly valuable insights into the control mechanisms of locomotion in primates, including humans.

Introduction: For decades, the saccadic system has been a favorite target of neurophysiologists seeking to elucidate the neural control of eye movements, partly because saccades are characterized by a set of highly stereotyped relationships between amplitude, duration, and peak velocity. There is a large literature describing the dynamics and trajectories of these movements in normal primates, but there are no similarly detailed analyses for subjects with infantile strabismus syndrome. Previous studies have shown the amplitudes and directions of saccades often differ for the two eyes in this disorder, but it is unknown whether a similar disconjugacy exists for duration. The present study was designed to determine whether or not saccade duration differs for the two eyes in strabismus, and whether there are abnormalities involving the trajectories of these movements. Methods: Dynamic analyses of saccade trajectories and durations were performed for two normal monkeys, two with esotropia and two with exotropia. The amount of curvature was compared for the two eyes. For each monkey with strabismus, the amount of curvature was compared to normal controls. Saccades were placed into 12 bins, based on direction; for each bin, the mean saccade duration was compared for the two eyes (duration disconjugacy). The duration disconjugacy for each bin was then compared for monkeys with strabismus, versus normal control animals. Results: Surprisingly, the amount of curvature was not consistently greater in subjects with pattern strabismus. However, saccade curvature differed for the two eyes by a significantly greater amount for all monkeys with strabismus, compared to normal controls. In addition, for a subset of saccades in subjects with strabismus, saccade duration differed for the two eyes by more than 10 ms, even when the animal was fully alert. Discussion: To the best of the author\'s knowledge, this is the first study to show that, in strabismus, saccade durations can differ for the two eyes by an abnormally large amount. These data also suggest that, in monkeys with pattern strabismus, abnormal horizontal-vertical crosstalk in brainstem can lead to directional disconjugacy without significantly impairing component stretching. These results place important constraints on future attempts to model the neural mechanisms that contribute to directional disconjugacy in pattern strabismus.