Greco, G. | Search bioRxiv

bioRxiv2022

CCR5 deficiency normalizes TIMP levels, working memory, and gamma oscillation power in APOE4 targeted replacement mice

The APOE4 allele increases the risk for Alzheimers disease (AD) in a dose-dependent manner and is also associated with cognitive decline in non-demented elderly controls. In mice with targeted gene replacement (TR) of murine APOE with human APOE3 or APOE4, the latter show reduced neuronal dendritic complexity and impaired learning. APOE4 TR mice also show reduced gamma oscillation power and sharp wave ripple (SWR) abundance, neuronal population activities important to learning and memory. Published work has shown that brain extracellular matrix (ECM) can reduce neuroplasticity as well as gamma power and SWR abundance, while attenuation of ECM can instead enhance these endpoints. In the present study we examine human cerebrospinal fluid (CSF) samples from APOE3 and APOE4 individuals and brain lysates from APOE3 and APOE4 TR mice for levels of ECM effectors that can increase matrix deposition and restrict neuroplasticity. We find that CCL5, a molecule linked to ECM deposition in liver and kidney, is increased in CSF samples from APOE4 individuals. Levels of tissue inhibitor of metalloproteinases (TIMPs), which inhibit the activity of ECM-degrading enzymes, are also increased in APOE4 CSF as well as protein lysates from APOE4 TR mice. Importantly, as compared to wildtype/APOE4 heterozygotes, CCR5 knockout/APOE4 heterozygotes show reduced TIMP levels and enhanced EEG gamma power. The latter also show improved learning and memory, suggesting that the CCR5/CCL5 axis could represent a therapeutic target for APOE4 individuals.

neuroscience↗

bioRxiv2020

Molecular detection of pathogens in ticks and fleas collected from companion dogs and cats in East and Southeast Asia

Ticks and fleas are considered amongst the most important arthropod vectors of medical and veterinary concern due to their ability to transmit pathogens to a range of animal species including dogs, cats and humans. By sharing a common environment with humans, companion animal-associated parasitic arthropods may potentially transmit zoonotic vector-borne pathogens (VBPs). This study aimed to molecularly detect pathogens from ticks (n = 392) and fleas (n = 248) collected from companion dogs and cats in East and Southeast Asia. Of the 392 ticks tested, 37 (9.4%) scored positive for at least one pathogen with Hepatozoon canis being the most prevalent (5.4%), followed by Ehrlichia canis (1.8%), Babesia vogeli (1%), Anaplasma platys (0.8%) and Rickettsia spp. (1%) [including Rickettsia sp. (0.5%), Rickettsia asembonensis (0.3%), Rickettsia felis (0.3%)]. Out of 248 fleas tested, 106 (42.7%) were harboring at least one pathogen with R. felis being the most common (19.4%), followed by Bartonella spp. (16.5%), Rickettsia asembonensis (10.9%) and Candidatus Rickettsia senegalensis (0.4%). Furthermore, 35 Rhipicephalus sanguineus sensu lato ticks were subjected to phylogenetic analysis, of which 34 ticks belonged to the tropical and only one belonged to the temperate lineage (Rh. sanguineus sensu stricto). Our data reveals the circulation of different VBPs in ticks and fleas of dogs and cats from Asia, including zoonotic agents, which may represent a potential risk to animal and human health. Author summaryTicks and fleas are among the most important vectors of pathogens infesting many animal species including humans worldwide. Although a number of vector-borne pathogens have been detected in dogs and cats from East and Southeast Asia, investigation in ticks and fleas collected from them are scant. In order to provide an overview of the pathogens circulating in ticks and fleas from companion dogs and cats in Asia, ticks (n = 392) and fleas (n = 248) were collected from privately-owned dogs and cats from China, Taiwan, Indonesia, Malaysia, Singapore, Thailand, Philippines and Vietnam and molecularly screened for the presence of pathogens. Overall, multiple pathogens were found in ticks (i.e., Babesia vogeli, Hepatozoon canis, Ehrlichia canis, Anaplasma platys and Rickettsia spp.) and fleas (i.e., Rickettsia spp. and Bartonella spp.) from the sampling areas. Of the ticks tested, 9.4% scored positive for at least one pathogen and of fleas 42.7% harbored at least one pathogen with Rickettsia felis being the most common (19.4%). Overall, of the detected pathogens, R. felis stood out as the most important due to its zoonotic potential. The result of this study should increase awareness among pet owners and veterinary practitioners regarding the importance of ticks and fleas, and their transmitted pathogens.

molecular biology↗