Pregnancies alters spine number in cortical and subcortical limbic brain regions of old rats

Abstract

Pregnancy is a complex process, involving a number of hormones and trophic factors, many of which are formed in the placenta. Several of these trophic factors have an effect at the neuronal level, such as BDNF. Consequently, recent reports have shown that exposure to these hormones (estrogen and progesterone) and trophic factors such as BDNF exert a neuroprotective effect. Here, we study the effect of the number of pregnancies on dendritic morphology of aged female rats (18 months of age). Rats of the 18‐month‐old Sprague Dawley strain with zero, one, two, and three gestations were evaluated for locomotor activity, and Golgi–Cox stain was performed to evaluate the dendritic morphology parameters, the number of dendritic spines, total dendritic length, and branching order number. Adult nulliparous rats (3 months of age) were used as another control group. Adult nulliparous and aging rats with two pregnancies showed an increase in locomotor activity. Adult nulliparous showed an increase in the dendritic spine number compared to old nulliparous rats in both layers of the PFC, the DG, and NAcc. Old rats with two and three pregnancies also showed an increase in the number of dendritic spines compared to old nulliparous rats in layers 3 and 5 of the PFC and in the CA1. Aging animals with one pregnancy also showed an increase in dendritic length compared to old nulliparous rats in the CA1. Our results clearly suggest that two and three pregnancies increase the dendritic spines number in the PFC and CA1 of aged female rats.

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

“…Previous reports have shown that aging caused a reduction in locomotor activity (Flores‐Vivaldo et al., 2019; Insgrama & Jucker, 1999; Lafoux, Baudry, Bonhomme, Le Ruyet, & Huchet, 2016; Yu, Xu, Song, Ji, & Zhang, 2013). For this reason, we analyzed whether the PBA has an effect on this type of behavior.…”

“…This cognitive improvement was not related to an increase in locomotor activity in a new environment. It is also well‐known that, like cognition, locomotive activity is also reduced with aging (Alcantara‐González et al, 2012; Flores‐Vivaldo et al., 2019; Insgrama & Jucker, 1999; Lafoux et al., 2016; Yu et al., 2013). However, our results suggest that the PBA did not modify locomotive activity in a novel environment in the old mice, despite producing an improvement in the number of dendritic spines and markers for synaptophysin without changes in the total dendritic length in the NAcc, a structure related to this behavior.…”

“…However, it is currently known that a large number of factors regulate the density of dendritic spines. Some of these factors are: neurotrophins, such as brain‐derived neural factor (BDNF), and nerve growth factor (NGF); hormones such as cortisol, estrogen, prolactin and growth hormone; neurotransmitters, such as glutamate, dopamine and serotonin; oxidative stress with an increase in nitric oxide (NO), reactive oxygen species (ROS) and protein nitrosylation; and also, inflammatory processes involving GFAP (Barreto‐Cordero et al., 2020; Bennett & Logopoulos, 2014; Flores et al., 2005; Flores‐Vivaldo et al., 2019; Olivares‐Hernandez, García‐García, Camacho‐Abrego, Flores, & Juárez‐Aguilar, 2018; Silva‐Gomez et al, 2003; Tellez‐Merlo et al., 2019). In addition, a recent report in an animal model of Alzheimer's disease also suggested that PBA increases the number of dendritic spines in the CA1 subfield of the hippocampus (Ricobaraza, Cuadrado‐Tejedor, Marco, Pérez‐Otaño, & García‐Osta, 2012).…”

“…Among the functional changes, cognitive deficits are the most transcendental. At the morphological level, the reduction of neuronal communication, especially at the dendritic level, has been evident (Flores‐Vivaldo, Camacho‐Abrego, Picazo, & Flores, 2019; Manczak, Kandimalla, Yin, & Reddy, 2018; Monroy, Diaz, Tendilla‐Beltrán, de la Cruz, & Flores, 2020). Analysis of the immunoreactivity of several presynaptic proteins, such as synaptophysin (Syp) have been used to evaluate how this occurs (Hernández‐Hernández et al., 2018; Saito et al., 1994; Tesic et al., 2017).…”

“…Both regions are interconnected by glutamatergic excitatory projections. These projections are made through pyramidal neurons, which are the main neurons in both regions (for review see Flores et al, 2019; Flores, Flores‐Gómez, et al, 2016; Flores, Morales‐Medina, et al, 2016). In addition, both regions send glutamatergic projections to the nucleus accumbens (NAcc), the structure known as the main reward center.…”