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In patients with Alzheimer's disease (AD) and in animal models, the increased accumulation of amyloid β (Aβ) in retinal blood vessels strongly correlates with brain amyloid deposits and cognitive decline. The accumulation of Aβ in blood vessels may result from impaired transcytosis and a dysfunctional ocular glymphatic system in AD. High-dose fish oil (FO) supplementation has been shown to significantly change the expression of major facilitator superfamily domain-containing protein 2a (Mfsd2a), a key regulator of transcytosis, and Aquaporin 4 (Aqp4), an essential component of the glymphatic system in the retinas of WT mice. We examined the expression of Mfsd2a and Aqp4 in the retinas of 4-month-old 5xFAD female mice supplemented with high-dose FO for three weeks. There was a significant increase in Mfsd2a expression in 5xFAD retinas supplemented with FO compared to control 5xFAD mice. Additionally, the increase in Aqp4 expression observed in 4-month-old 5xFAD retinas, indicative of an impaired glymphatic system, was significantly decreased. Simultaneously, Aβ accumulation in 5xFAD retinal blood vessels was reduced following FO supplementation. These findings suggest that high-dose FO supplementation could serve as an adjunct in developing new treatments aimed at improving the regulation of transcytosis or the function of the glymphatic system in the AD retina. [ABSTRACT FROM AUTHOR]

Introduction: In the present study, we assessed the effects of the hyper‐harmonized‐hydroxylated fullerene–water complex (3HFWC) on Alzheimer's disease (AD) neuropathological hallmarks in 5XFAD mice, an AD animal model. Methods: The 3‐week‐old 5XFAD mice were exposed to 3HFWC water solution ad libitum for 3 months in the presymptomatic phase of pathology. The functional effects of the treatment were confirmed through near‐infrared spectroscopy (NIRS) analysis through machine learning (ML) using artificial neural networks (ANNs) to classify the control and 3HFWC‐treated brain tissue samples. The effects of 3HFWC treatment on amyloid‐β (Aβ) accumulation, plaque formation, gliosis, and synaptic plasticity in cortical and hippocampal tissue were assessed. Results: The 3HFWC treatment significantly decreased the amyloid‐β plaque load in specific parts of the cerebral cortex. At the same time, 3HFWC treatment did not induce the activation of glia (astrocytes and microglia) nor did it negatively affect synaptic protein markers (GAP‐43, synaptophysin, and PSD‐95). Conclusion: The obtained results point to the potential of 3HFWC, when applied in the presymptomatic phase of AD, to interfere with amyloid plaque formation without inducing AD‐related pathological processes such as neuroinflammation, gliosis, and synaptic vulnerability. [ABSTRACT FROM AUTHOR]

In the olfactory epithelium (OE), generation of new neurons by neuronal progenitors is inhibited by a signal from neurons themselves. Here we provide evidence that this feedback inhibitory signal is growth and differentiation factor 11 (GDF11). Both GDF11 and its receptors are expressed by OE neurons and progenitors, and GDF11 inhibits OE neurogenesis in vitro by inducing p27(Kip1) and reversible cell cycle arrest in progenitors. Mice lacking functional GDF11 have more progenitors and neurons in the OE, whereas mice lacking follistatin, a GDF11 antagonist, show dramatically decreased neurogenesis. This negative autoregulatory action of GDF11 is strikingly like that of its homolog, GDF8/myostatin, in skeletal muscle, suggesting that similar strategies establish and maintain proper cell number during neural and muscular development.