Phenylbutyrate ameliorates prefrontal cortex, hippocampus, and nucleus accumbens neural atrophy as well as synaptophysin and GFAP stress in aging mice

Abstract

Recent reports on brain aging suggest that oxidative stress and inflammatory processes contribute to aging. Interestingly, sodium phenylbutyrate (PBA) is an inhibitor of histone deacetylase, which has anti‐inflammatory properties. Several reports have suggested the effect of PBA on learning and memory processes, however there are no studies of the effect of this inhibitor of histone deacetylase on aging. Consequently, in the present study, the effect of PBA was studied in 18‐month‐old mice. The animals were administered PBA for 2 months after locomotor activity treatment and Morris water maze tests were performed. The Golgi‐Cox staining technique and immunohistochemistry for glial fibrillary acidic protein (GFAP) and synaptophysin were performed for the morphological procedures. The administration of PBA improves learning and memory according to the Morris water maze test compared to vehicle‐treated animals, which had unchanged locomotor activity. Using Golgi‐Cox staining, dendritic length and the number of dendritic spines were measured in limbic regions, such as the nucleus accumbens (NAcc), prefrontal cortex (PFC) layer 3, and the CA1 of the dorsal hippocampus. In addition, PBA increased the number of dendritic spines in the PFC, NAcc, and CA1 subregions of the hippocampus with an increase in dendritic length only in the CA1 region. Moreover, PBA reduced the levels of the GFAP and increased the levels of synaptophysin in the studied regions. Thus, PBA can be a useful pharmacological tool to prevent or delay synaptic plasticity damage and cognitive impairment caused by age.

The protective role of l-carnitine on oxidative stress, neurotransmitter perturbations, astrogliosis, and apoptosis induced by thiamethoxam in the brains of male rats

“…These changes may indicate higher dopaminergic and serotonergic turnover in the brain (Abd-Elhakim et al 2018 ). Furthermore, oxidative stress and free radical production are increased because astrocytes, which maintain the integrity of the blood˗brain barrier, are targets of oxidative damage (Carvajal-Flores et al 2020 ; Fulton et al 2021 ).…”

The C‐terminal fragment of the heavy chain of the tetanus toxin (Hc‐TeTx) improves motor activity and neuronal morphology in the limbic system of aged mice

“…(2020) and Carvajal‐Flores et al. (2020). Locomotor activity was monitored in individual cages (20 cm × 40 cm × 30 cm), equipped with an eight‐photo‐beam detector connected to a computer counter (Technology Digital, México).…”

“…The locomotor activity test was evaluated thirty days after the injection of the Hc-TeTx fragment. Assays were performed according to Monroy et al (2020) and Carvajal-Flores et al (2020). Locomotor activity was monitored in individual cages (20 cm × 40 cm × 30 cm), equipped with an eight-photo-beam detector connected to a computer counter (Technology Digital, México).…”

A cocktail of rapamycin, acarbose, and phenylbutyrate prevents age-related cognitive decline in mice by targeting multiple aging pathways

“…Aberrant progression of several critical pathways accelerates biological aging. Pathways including mammalian target of rapamycin (mTOR) signaling, insulin signaling, and histone deacetylation [1] are respectively and individually targeted by rapamycin (Rap), acarbose (Acb), and phenylbutyrate (Pba), with each drug shown to have anti-aging effects in mice [2][3][4][5][6]. A combination of these three drugs as a cocktail would be expected to result in a more robust outcome on preventing or Abstract Aging is a primary risk factor for cognitive impairment and exacerbates multiple biological processes in the brain, including but not limited to nutrient sensing, insulin signaling, and histone deacetylation activity.…”