Hyperammonemia induced gut microbiota dysbiosis and motor coordination disturbances in mice: new insight into gut­brain axis involvement in hepatic encephalopathy.

Hepatic encephalopathy (HE) is a neuropsychiatric hepatic­induced syndrome in which several factors are involved in promoting brain perturbations, with ammonia being the primary factor. Motor impairment, incoordination, and gut dysbiosis are some of the well­known symptoms of HE. Nevertheless, the link between the direct effect of hyperammonemia and associated gut dysbiosis in the pathogenesis of HE is not well established. Thus, this work aimed to assess motor function in hyperammonemia and gut dysbiosis in mice. Twenty­eight Swiss mice were distributed into three groups: two­week and four­week hyperammonemia groups were fed with an ammonia­rich diet (20% w/w), and the control group was pair­fed with a standard diet. Motor performance in the three groups was measured through a battery of motor tests, namely the rotarod, parallel bars, beam walk, and static bars. Microbial analysis was then carried out on the intestine of the studied mice. The result showed motor impairments in both hyperammonemia groups. Qualitative and quantitative microbiological analysis revealed decreased bacterial load, diversity, and ratios of both aerobic and facultative anaerobic bacteria, following two and four weeks of ammonia supplementation. Moreover, the Shannon diversity index revealed a time­dependent cutback of gut bacterial diversity in a treatment­time­dependent manner, with the presence of only Enterobacteriaceae, Streptococcaceae, and Enterococcaceaeat at four weeks. The data showed that ammonia­induced motor coordination deficits may develop through direct and indirect pathways acting on the gut­brain axis.

Sensory Motor Function Disturbances in Mice Prenatally Exposed to Low Dose of Ethanol: A Neurobehavioral Study in Postnatal and Adult Stages.

Prenatal alcohol exposure (PAE) refers to fetal exposure to alcohol during pregnancy through placental barrier transfer from maternal blood. The postnatal outcomes of PAE differ among exposed individuals and range from overt (serious) alcohol-related behavioral and neurophysiological impairments to covert (silenced) symptoms. The aims of the present investigation were to assess the postnatal neurobehavioral disturbances, particularly, motor coordination and sensory-motor function in mice with PAE. Female mice with positive vaginal plugs were divided into three groups: group 1: Et + Pyr: received two i.p injections of ethanol (1 g/kg) followed by pyrazole (100 mg/kg). Group 2: Pyr: received an i.p injection of pyrazole (100 mg/kg). Group 3: C: of saline controls received, in equal volume, saline solution (NaCl 0.9%). After birth, mice pups were weighed and subjected to behavioral tests for motor function screening using the motor ambulation test, cliff aversion, surface righting, and negative geotaxis, while at the adult stage, mice were subjected to the open field, rotarod, parallel bars, and static rods tests. Our data show an obvious decrement of body weight from the first post-natal day (P1) and continues over the adult stage. This was accompanied by an obvious impaired sensory-motor function which was maintained even at the adult stage with alteration of the locomotor and coordination abilities. The current data demonstrate the powerful neurotoxic effect of prenatal ethanol exposure on the sensory-motor and coordination functions, leading to suppose possible structural and/or functional neuronal disturbances, particularly the locomotor network.

Maternal prenatal stress in rats influences c-fos expression in the spinal cord of the offspring.

Previous studies in humans have reported a link between maternal stress and disturbed infant physiological behavior. The objective of our study was to examine in experimental rats how maternal prenatal stress induced by a forced swim test affects offspring afferent spinal responses mediated by stimulation of vaginocervical receptors. The activation of spinal cord neurons showing c-fos expression was examined following vaginocervical mechanical stimulation in adult rats, which were the offspring of dams exposed to gestational stress from E10 until delivery. Vaginocervical stimulation of both prenatal-stressed and non-prenatal-stressed rats induced an increase in immunoreactive protein in the spinal cord ranging from T12 to S1 segmental levels. However, a significantly higher (40%) increase in the expression of Fos-immunoreactive neurons was observed in vaginocervical stimulated prenatally stressed rats than in non-stimulated prenatally stressed ones. This increase was higher in L5-S1 levels than in T12-L4. When the regional distribution was examined, results showed that up to 80% of activated neurons were located in the dorsal horn in both non-stimulated prenatally stressed and stimulated prenatally stressed groups, with a significantly higher density in the latter. Our results demonstrate that maternal prenatal stress can have consequences on vaginocervical responses conveyed to the spinal cord. The increase in Fos labeled neurons in T12-S1 in prenatally stressed rats induced by vaginocervical stimulation suggests the hypersensitivity of the genital tract associated with activation of spinal circuits spanning multiple segments.