Phenylbutyrate ameliorates prefrontal cortex, hippocampus, and nucleus accumbens neural atrophy as well as synaptophysin and GFAP stress in aging mice. Issue 11 (1st July 2020)

• Record Type: Journal Article
• Authors: Carvajal‐Flores, Fabiola Natividad; Díaz, Alfonso; Flores‐Gómez, Gabriel D.; de la Cruz, Fidel; Flores, Gonzalo
• Is Part Of: Synapse. Volume 74:Issue 11(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-07-01
• Subjects: aging -- dendrites -- hippocampus -- memory and learning -- nucleus accumbens -- prefrontal cortex -- sodium phenylbutyrate; Synapses -- Periodicals; 612
• DOI: 10.1002/syn.22177
• Languages: English
• ISSNs: 0887-4476

Abstract

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. Abstract : Phenylbutyrate treatment improves the learning and memory in the old mice. Phenylbutyrate treatment increases the number of dendritic spines in the PFC, NAcc, and hippocampus of old animals. Phenylbutyrate also increases the dendritic arborization in the hippocampus of old mice. Phenylbutyrate also increases synaptophysin and decreases the GFAP levels in the observed regions of the old animals. Phenylbutyrate improves synaptic plasticity and cognitive decline in aged animals.