Search

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 co-localized 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.

Symptoms of Parkinson's disease (PD) caused by loss of dopaminergic neurons are accompanied by movement disorders, including tremors, rigidity, bradykinesia, and akinesia. Non-human primate (NHP) models with PD play an essential role in the analysis of PD pathophysiology and behavior symptoms. As impairments of hand dexterity function can affect activities of daily living in patients with PD, research on hand dexterity function in NHP models with chronic PD is essential. Traditional rating scales previously used in the evaluation of animal spontaneous behavior were insufficient due to factors related to subjectivity and passivity. Thus, experimentally designed applications for an appropriate apparatus are necessary. In this study, we aimed to longitudinally assess hand dexterity function using hand dexterity task (HDT) in NHP-PD models. To validate this assessment, we analyzed the alteration in Parkinsonian tremor signs and the functionality of presynaptic dopaminergic neuron using positron emission tomography imaging of dopamine transporters in these models. In addition, a significant inverse correlation between HDT and DAT level was identified, but no local bias was found. The correlation with intention tremor signs was lower than the resting tremor. In conclusion, the evaluation of HDT may reflect behavioral symptoms of NHP-PD models. Furthermore, HDT was effectively used to experimentally distinguish intention tremors from other tremors.

Chemotherapeutic agents induce long-term side effects, including cognitive impairment and mood disorders, particularly in breast cancer survivors who have undergone chemotherapy. However, the precise mechanisms underpinning chemotherapy-induced hippocampal dysfunction remain unknown. In this study, we investigated the detrimental effects of chronic treatment with a combination of adriamycin and cyclophosphamide (AC) on the neuronal architecture and functions of the hippocampi of female C57BL/6 mice. After chronic AC administration, mice showed memory impairment (measured using a novel object recognition memory task) and depression-like behavior (measured using the tail suspension test and forced swim test). According to Golgi staining, chronic AC treatment significantly reduced the total dendritic length, ramification, and complexity as well as spine density and maturation in hippocampal neurons in a sub-region-specific manner. Additionally, the AC combination significantly reduced adult neurogenesis, the extent of the vascular network, and the levels of hippocampal angiogenesis-related factors. However, chronic AC treatment did not increase the levels of inflammation-related signals (microglial or astrocytic distribution, or the levels of pro-inflammatory cytokines or M1/M2 macrophage markers). Thus, chronic AC treatment changed the neuronal architecture of the adult hippocampus, possibly by reducing neurogenesis and the extent of the vasculature, independently of neuroinflammation. Such detrimental changes in micromorphometric parameters may explain the hippocampal dysfunction observed after cancer chemotherapy., Graphical Abstract