Dysregulated C1q and CD47 in the aging monkey brain: association with myelin damage, microglia reactivity, and cognitive decline.

Normal aging, though lacking widespread neurodegeneration, is nevertheless characterized by cognitive impairment in learning, memory, and executive function. The aged brain is spared from neuron loss, but white matter is lost and damage to myelin sheaths accumulates. This myelin damage is strongly associated with cognitive impairment.

White matter lipid alterations during aging in the rhesus monkey brain.

The brain of higher organisms, such as nonhuman primates, is particularly rich in lipids, with a gray to white matter ratio of approximately 40 to 60%. White matter primarily consists of lipids, and during normal aging, it undergoes significant degeneration due to myelin pathology, which includes structural abnormalities, like sheath splitting, and local inflammation. Cognitive decline in normal aging, without neurodegenerative diseases, is strongly linked to myelin pathology.

Long-term calorie restriction reduces oxidative DNA damage to oligodendroglia and promotes homeostatic microglia in the aging monkey brain.

Calorie restriction (CR) is a robust intervention that can slow biological aging and extend lifespan. In the brain, terminally differentiated neurons and glia accumulate oxidative damage with age, reducing their optimal function. We investigated if CR could reduce oxidative DNA damage to white matter oligodendrocytes and microglia.

Neuroanatomical Substrates of Circuit-Specific Cholinergic Modulation across the Primate Anterior Cingulate Cortex.

Acetylcholine is a robust neuromodulator of the limbic system and a critical regulator of arousal and emotions. The anterior cingulate cortex (ACC) and the amygdala (AMY) are key limbic structures that are both densely innervated by cholinergic afferents and interact with each other for emotional regulation. The ACC is composed of functionally distinct dorsal (A24), rostral (A32), and ventral (A25) areas that differ in their connections with the AMY.

Enhanced Multiscale Human Brain Imaging by Semi-supervised Digital Staining and Serial Sectioning Optical Coherence Tomography.

A major challenge in neuroscience is to visualize the structure of the human brain at different scales. Traditional histology reveals micro- and meso-scale brain features, but suffers from staining variability, tissue damage and distortion that impedes accurate 3D reconstructions. Here, we present a new 3D imaging framework that combines serial sectioning optical coherence tomography (S-OCT) with a deep-learning digital staining (DS) model.

Comparison of monkey and human retrosplenial neurocytology.

Retrosplenial cortex (RSC) has unique problems for human neuroimaging studies as its divisions are small, at the lower end of functional scanner spatial resolution, and it is buried in the callosal sulcus. The present study sought to define the cytoarchitecture of RSC in human and monkey brains along its entire anteroposterior extent. The results show anterior extensions, a newly defined dichotomy of area 30, a new area p30, and an area p29v in monkey that differentiates into three divisions in human.

Human-to-monkey transfer learning identifies the frontal white matter as a key determinant for predicting monkey brain age.

The application of artificial intelligence (AI) to summarize a whole-brain magnetic resonance image (MRI) into an effective "brain age" metric can provide a holistic, individualized, and objective view of how the brain interacts with various factors (e.g., genetics and lifestyle) during aging.

Immune proteins C1q and CD47 may contribute to aberrant microglia-mediated synapse loss in the aging monkey brain that is associated with cognitive impairment.

Cognitive impairment in learning, memory, and executive function occurs in normal aging even in the absence of Alzheimer's disease (AD). While neurons do not degenerate in humans or monkeys free of AD, there are structural changes including synapse loss and dendritic atrophy, especially in the dorsolateral prefrontal cortex (dlPFC), and these correlate with cognitive age-related impairment. Developmental studies revealed activity-dependent neuronal properties that lead to synapse remodeling by microglia.

Pattern of ventral temporal lobe interconnections in rhesus macaques.

The entorhinal cortex (EC, A28) is linked through reciprocal pathways with nearby perirhinal and visual, auditory, and multimodal association cortices in the temporal lobe, in pathways associated with the flow of information for memory processing. The density and laminar organization of these pathways is not well understood in primates. We studied interconnections within the ventral temporal lobe in young adult rhesus monkeys of both sexes with the aid of neural tracers injected in temporal areas (Ts1, Ts2, TE1, area 36, temporal polar area TPro, and area 28) to determine the density and laminar distribution of projection neurons within the temporal lobe.

Mesenchymal-derived extracellular vesicles enhance microglia-mediated synapse remodeling after cortical injury in aging Rhesus monkeys.

Understanding the microglial neuro-immune interactions in the primate brain is vital to developing therapeutics for cortical injury, such as stroke or traumatic brain injury. Our previous work showed that mesenchymal-derived extracellular vesicles (MSC-EVs) enhanced motor recovery in aged rhesus monkeys following injury of primary motor cortex (M1), by promoting homeostatic ramified microglia, reducing injury-related neuronal hyperexcitability, and enhancing synaptic plasticity in perilesional cortices. A focal lesion was induced via surgical ablation of pial blood vessels over lying the cortical hand representation of M1 of aged female rhesus monkeys, that received intravenous infusions of either vehicle (veh) or EVs 24 h and again 14 days post-injury.

Neuronal properties of pyramidal cells in lateral prefrontal cortex of the aging rhesus monkey brain are associated with performance deficits on spatial working memory but not executive function.

Age-related declines in cognitive abilities occur as early as middle-age in humans and rhesus monkeys. Specifically, performance by aged individuals on tasks of executive function (EF) and working memory (WM) is characterized by greater frequency of errors, shorter memory spans, increased frequency of perseverative responses, impaired use of feedback and reduced speed of processing. However, how aging precisely differentially impacts specific aspects of these cognitive functions and the distinct brain areas mediating cognition are not well understood.

Prefrontal and medial temporal interactions in memory functions in the rhesus monkey.

Both the medial temporal lobe and the dorsolateral prefrontal cortex have been implicated in learning and memory. However, it has been difficult to ascertain the degree to which the two structures are dependent on each other or interact in subserving these cognitive functions. To investigate this question directly, we prepared two group of monkeys.

Neuronal properties of pyramidal cells in lateral prefrontal cortex of the aging rhesus monkey brain are associated with performance deficits on spatial working memory but not executive function.

Age-related declines in cognitive abilities occur as early as middle-age in humans and rhesus monkeys. Specifically, performance by aged individuals on tasks of executive function (EF) and working memory (WM) is characterized by greater frequency of errors, shorter memory spans, increased frequency of perseverative responses, impaired use of feedback and reduced speed of processing. However, how aging precisely differentially impacts specific aspects of these cognitive functions and the distinct brain areas mediating cognition are not well understood.

Vascular Collagen Type-IV in Hypertension and Cerebral Small Vessel Disease.

Background: Cerebral small vessel disease (SVD) is common in older people and causes lacunar stroke and vascular cognitive impairment. Risk factors include old age, hypertension and variants in the genes encoding collagen alpha-1(IV) and alpha-2(IV), here termed collagen-IV, which are core components of the basement membrane. We tested the hypothesis that increased vascular collagen-IV associates with clinical hypertension and with SVD in older persons and with chronic hypertension in young and aged primates and genetically hypertensive rats.

Aging compromises oligodendrocyte precursor cell maturation and efficient remyelination in the monkey brain.

Age-associated cognitive decline is common among otherwise healthy elderly people, even in the absence of Alzheimer's disease and neuron loss. Instead, white matter loss and myelin damage are strongly associated with cognitive decline. Myelin is subject to lifelong oxidative stress that damages the myelin sheath, which is repaired by cells of the oligodendrocyte lineage.

Morphology and unbiased stereology of the lateral superior olive in the short-beaked common dolphin, Delphinus delphis (Cetacea, Delphinidae).

In all mammals, the superior olivary complex (SOC) comprises a group of auditory brainstem nuclei that are important for sound localization. Its principal nuclei, the lateral superior olive (LSO) and the medial superior olive (MSO) process interaural time and intensity differences, which are the main cues for sound localization in the horizontal plane. Toothed whales (odontocetes) rely heavily on hearing and echolocation for foraging, orientation, and communication and localize sound with great acuity.

Specializations of somatosensory innervation in the skin of humpback whales (Megaptera novaeangliae).

Cetacean behavior and life history imply a role for somatosensory detection of critical signals unique to their marine environment. As the sensory anatomy of cetacean glabrous skin has not been fully explored, skin biopsy samples of the flank skin of humpback whales were prepared for general histological and immunohistochemical (IHC) analyses of innervation in this study. Histology revealed an exceptionally thick epidermis interdigitated by numerous, closely spaced long, thin diameter penicillate dermal papillae (PDP).

Curcumin improves reversal learning in middle-aged rhesus monkeys.

Age-related impairments in cognitive function occur in multiple animal species including humans and nonhuman primates. Humans and rhesus monkeys exhibit a similar pattern of cognitive decline beginning in middle age, particularly within the domain of executive function. The prefrontal cortex is the brain region most closely associated with mediating executive function.

Exosomes derived from bone marrow mesenchymal stromal cells promote remyelination and reduce neuroinflammation in the demyelinating central nervous system.

Injury of oligodendrocytes (OLs) induces demyelination, and patients with neurodegenerative diseases exhibit demyelination concomitantly with neurological deficit and cognitive impairment. Oligodendrocyte progenitor cells (OPCs) are present in the adult central nervous system (CNS), and they can proliferate, differentiate, and remyelinate axons after damage. However, remyelination therapies are not in clinical use.

Sex differences in recovery of motor function in a rhesus monkey model of cortical injury.

Background: Stroke disproportionately affects men and women, with women over 65 years experiencing increased severity of impairment and higher mortality rates than men. Human studies have explored risk factors that contribute to these differences, but additional research is needed to investigate how sex differences affect functional recovery and hence the severity of impairment. In the present study, we used our rhesus monkey model of cortical injury and fine motor impairment to compare sex differences in the rate and degree of motor recovery following this injury.

Layer-specific pyramidal neuron properties underlie diverse anterior cingulate cortical motor and limbic networks.

The laminar cellular and circuit mechanisms by which the anterior cingulate cortex (ACC) exerts flexible control of motor and affective information for goal-directed behavior have not been elucidated. Using multimodal tract-tracing, in vitro patch-clamp recording and computational approaches in rhesus monkeys (M. mulatta), we provide evidence that specialized motor and affective network dynamics can be conferred by layer-specific biophysical and structural properties of ACC pyramidal neurons targeting two key downstream structures -the dorsal premotor cortex (PMd) and the amygdala (AMY).