Alterations in the dentate gyrus of the offspring of rats treated with alprazolam during gestation.

Benzodiazepine (BZD) abuse is a global problem, including pregnant women. For this population, the drug of choice is usually alprazolam, which acts as a GABAergic agonist and may compromise the development of integrative areas of the nervous system, such as the dentate gyrus (DG) of the hippocampus. In this context, we studied the changes in the DG of the offspring of rats treated with alprazolam during gestation: control, treatment 1 (T1: 1.25 mg/animal), and an overdose group (T2: 30 mg/animal). Alprazolam was administered orally ten days before mating and during the gestational period. After birth, newborns were counted, sexed, and the body mass of each pup was measured. The newborns' brains were extracted and processed for morphological study of the DG or for total protein extraction of the hippocampus. The results showed that alprazolam can affect the cell number and area, and increased euchromatin in both granular and molecular layers of the DG, especially in the overdose group. Also, alprazolam upregulated the NF-κB and reduced GFAP and caspase-3. Based on our findings, we conclude that the DG is a plausible region of influence by BZDs during embryogenesis. An overdose during gestation may cause structural changes in the DG.

Prenatal effects of alprazolam treatment on the immature cerebellum of rats.

The use of benzodiazepines (BZDs) during pregnancy, especially alprazolam, is common and its impact on the fetal neural tissue is not known. In this sense, the present study aimed to investigate the effects of prenatal treatment with alprazolam on the cerebellum of Wistar rat pups. Thirty animals (24 females and six males, CEUA protocol 014/17) were separated into pairs for copulation. Females were divided into three groups: Control (CT), treatment 1 (T1, 1.25 mg per animal), and treatment 2, which is an overdose (T2, 30 mg per animal). Alprazolam was administered 10 days before copulation and throughout pregnancy. We evaluated the number and weight of pups and the macroscopic changes in the brain. Eight neonates (n = 8) from each group were used in the following analyses: Cellular and chromatin density, gliosis, synaptic density, inflammation, and oxidative stress. The results showed no significant differences regarding the number of pups, body weight, and macroscopic changes. The morphological study focused on the external granular layer (EGL) that is presented only in the immature cerebellum. Here, we detected more cells after alprazolam treatment; the T2 group showed large nuclei and some pyknotic nuclei; also, both treated groups presented an increase in the euchromatin density compared with the control. The molecular and biochemical analyses used the total protein extract of the entire cerebellum and showed an increased expression of Iba-1 and NF-κBp65 but without indication of inflammation or degeneration in the T1 group. Overdose of alprazolam presented an increased level of oxidative degradation of lipids. The treatment with alprazolam during pregnancy involved cellular and molecular changes in the immature cerebellum.

Angiotensin-(1-7) receptor Mas antagonist (A779) influenced gliosis and reduced synaptic density in the spinal cord after peripheral axotomy.

The peptide angiotensin-(1-7) [Ang (1-7)] and its receptor Mas are involved in controlling arterial pressure and display actions on the nervous system. In a previous study, our laboratory showed that A779 [(peptidyl antagonist of the Ang-(1-7)] treatment had a negative effect following a lesion of the sciatic nerve, possibly by delaying the responses of Schwann cells, resulting in a decreased axonal organization along with a slowed functional return. In the present work, we investigated the central cellular changes after sciatic nerve injury in rodents treated with A779 after two weeks. In the lumbar spinal cords, where the neuronal bodies that make up the sciatic are, the treatment with A779 showed reduced reactivity of astrocytes (p = 0.004, Mann-Whitney U test) and less synaptic density (p = 0.004, Mann-Whitney U test) after injury. Also, the treatment upregulated microglia activity in both sides (p = 0.004, Mann-Whitney U test), ipsilateral and contralateral to the lesion, of the spinal cord. In addition, the Mas expression in spine neurons was increased in response to axotomy especially after two weeks (p = 0.03, Mann-Whitney U test) following the nerve lesion in comparison to earlier stages after injury. Therefore, we can conclude that Ang-(1-7)/Mas axis plays a role during spinal cord recovery after peripheral nerve injury.