Rauf, A. | Search bioRxiv

bioRxiv2025

Peripheral Neuropathy After Chronic Alcohol Exposure in Mice: Impact of sex, total intake and duration and alcohol metabolism.

Alcohol induced peripheral neuropathy (AIPN) is a neurodegenerative disease caused by chronic alcohol intake and is associated with peripheral nerve damage and somatosensory symptoms, such as allodynia. Current treatments lack efficacy and do not target underlying pathology emphasizing the need for preclinical models of AIPN to elucidate mechanisms and novel targets. Thus, we performed a detailed characterization of a mouse model of AIPN and candidate mechanistic associations including the role of neuroinflammation and acetaldehyde. Our studies showed chronic alcohol induced mechanical and cold hypersensitivity and deficits in spontaneous behaviors in EtOH concentration-, time- and sex-dependent manners. Female mice drank more alcohol and developed more rapid and severe hypersensitivity but less robust deficits of spontaneous behaviors. The grimace test demonstrated chronic alcohol promoted spontaneous pain independent of sex. Duration of intake impacted alcohol-induced deficits in peripheral nerve electrophysiology amplitude and intra-epidermal nerve fiber density. We characterized an extensive time-course of chronic alcohol-induced neuroinflammation in the DRG and spinal cord and found significant time, sex and tissue effects. Polymorphisms of ALDH2 have been associated with alcohol-induced neuroinflammation, alcohol-related pain, and alcohol-induced peripheral neuropathy. We investigated the role of acetaldehyde, via inhibition of ALDH2, in the development of AIPN and showed that ALDH2 inhibition accelerated and exacerbated development of chronic alcohol-induced hypersensitivity in male and female mice. Overall, our studies in a well-controlled model of AIPN strongly point to neuroinflammation and inflammatory modulators such as acetaldehyde as important mechanistic targets for possible intervention in AIPN.

pharmacology and toxicology↗

bioRxiv2021

Malathion-resistant Tribolium castaneum has enhanced response to oxidative stress, immunity, and fitness

Many cases of insecticide resistance in insect pests give resulting no-cost strains that retain the resistance genes even in the absence of the toxic stressor. Malathion has been widely used against the red flour beetle, Tribolium castaneum Herbst. in stored products although no longer used. Malathion specific resistance in this pest has provided resistance that is long lasting and widely distributed. To understand this resistance a malathion resistant strain was challenged with a range of stressors including starvation, hyperoxia, malathion and a pathogen and the antioxidant responses and some lifecycle parameters were determined. Adult life span of malathion-specific resistant strain of T. castaneum was significantly shorter than the susceptible. Starvation and/or high oxygen reduced adult life span of both strains. Starving with and without 100% oxygen gave longer lifespan for the resistant strain, but for oxygen alone there was no difference. Under oxygen the proportional survival of the resistant strain to the adult stage was significantly higher, for both larvae and pupae, than the susceptible. The resistant strain when stressed with malathion and/or oxygen significantly increased catalase activity, but the susceptible did not. The resistant strain stressed with Paranosema whitei infection had significantly higher survival compared to the susceptible, and with almost no mortality. The malathion resistant strain of T. castaneum showed greater vigour than the susceptible in most oxidative stress situations and especially where stressors were combined. The induction of the antioxidant enzyme catalase could have helped the resistant strain to withstand oxidative stresses, including insecticidal and importantly those from pathogens. These adaptations, in the absence of insecticide, seem to support the increased immunity of host insects to pathogens seen in other insect species, such as mosquitoes. By increasing the responses to a range of stressors the resistant strain could be considered as having enhanced fitness.

zoology↗