Chronic administration of resveratrol prevents morphological changes in prefrontal cortex and hippocampus of aged rats

Abstract

Resveratrol may induce its neuroprotective effects by reducing oxidative damage and chronic inflammation apart from improving vascular function and activating longevity genes, it also has the ability to promote the activity of neurotrophic factors. Morphological changes in dendrites of the pyramidal neurons of the prefrontal cortex (PFC) and hippocampus have been reported in the brain of aging humans, or in humans with neurodegenerative diseases such as Alzheimer's disease. These changes are reflected particularly in the decrement of both the dendritic tree and spine density. Here we evaluated the effect of resveratrol on the dendrites of pyramidal neurons of the PFC (Layers 3 and 5), CA1- and CA3-dorsal hippocampus (DH) as well as CA1-ventral hippocampus, dentate gyrus (DG), and medium spiny neurons of the nucleus accumbens of aged rats. 18-month-old rats were administered resveratrol (20 mg/kg, orally) daily for 60 days. Dendritic morphology was studied by the Golgi-Cox stain procedure, followed by Sholl analysis on 20-month-old rats. In all resveratrol-treated rats, a significant increase in dendritic length and spine density in pyramidal neurons of the PFC, CA1, and CA3 of DH was observed. Interestingly, the enhancement in dendritic length was close to the soma in pyramidal neurons of the PFC, whereas in neurons of the DH and DG, the increase in dendritic length was further from the soma. Our results suggest that resveratrol induces modifications of dendritic morphology in the PFC, DH, and DG. These changes may explain the therapeutic effect of resveratrol in aging and in Alzheimer's disease.

Voluntary Exercise Promotes Glymphatic Clearance of Amyloid Beta and Reduces the Activation of Astrocytes and Microglia in Aged Mice

“…However, microglia can also modulate the synaptic function by secreting cytokines, hormones, or growth factors (Wake et al, 2013). A previous study reported that both the dendritic tree and dendritic spine density in the cortex and hippocampus decrease during aging (Monserrat Hernández-Hernández et al, 2016). As well as reduced microglial activation in the cortex and hippocampus, the expression of GFP-labeled pyramidal neurons and their arbors was increased in the running group, suggesting that physical training prevents microglial activation and the loss of synapsis.…”

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

“…When comparing the effect of PBA with other products such as resveratrol, similar results have been reported in relation to dendritic morphology in elderly animals (Hernández‐Hernández et al., 2016) and in rats with mild traumatic brain injury (Salberg, Yamakawa, Christensen, Kolb, & Mychasiuk, 2017). In addition, resveratrol also increases BDNF levels (Rahvar, 2011), a neurotrophin that regulates dendritic spines (for review see von Bohlen Und Halbach & von Bohlen Und Halbach, 2018).…”

The aminoestrogen prolame increases recognition memory and hippocampal neuronal spine density in aged mice

“…The results indicate that prolame treatment causes changes in the dendritic morphology of aged mice, especially in the pyramidal neurons of the CA1 and CA3 as well as granule cells of DG subfields of the HP. Both brain regions are of cognitive interest, and in aging models show a reduction in dendritic spines density and dendritic length (Alcantara‐Gonzalez et al, 2012; Hernández‐Hernández et al, ), because they are highly susceptible to oxidative stress, inflammatory response and apoptosis, which cause neuronal death (Mattson & Magnus, ). Several reports have suggested that subjecting animals to learning and memory tests, such as the NORT test, may induce an increase in the number of dendritic spines (Cercato et al, ; Hara, Rapp, & Morrison, ; Kolb & Whishaw, ; Penagos‐Corzo, Bonilla, Rodríguez‐Moreno, Flores, & Negrete‐Díaz, ).…”

“…Aging deteriorates the neuronal function eliciting oxidative stress and inflammation in cognitive and motor regions in the hippocampus (HP) and nucleus accumbens (NAcc). These trigger processes of neurogenesis and neuronal repair inhibition (Hernández‐Hernández et al, ). The circulating and local brain estrogen concentration is considerably reduced in aging (Pratap et al, ), thus negatively influencing the intensity and duration of inflammatory and oxidative processes (Alabarse et al ) that dramatically compromise the viability of neurons in the HP, cerebral cortex and NAcc (Bayer et al, ; Yamaguchi‐Shima & Yuri, ).…”