Bexarotene treatment increases dendritic length in the nucleus accumbens without change in the locomotor activity and memory behaviors, in old mice.

The aged brain has biochemical and morphological alterations in the dendrites of the pyramidal neurons of the limbic system, which consequently trigger motor and cognitive deficits. Bexarotene 4-[1-(3,5,5,8,8-pentamethyl-6,7-dihydronaphthalen-2-yl)ethenyl]benzoic acid is a selective agonist of X-retinoid receptors which acts by binding to the intracellular retinoic acid receptors (RAR). It decreases oxidative and inflammatory activity, in addition to the transport of lipids, mechanisms that together could have a neuroprotective effect. Our objective was to evaluate the effect of bexarotene on the motor and cognitive processes, as well as its influence on the dendritic morphology of neurons in the limbic system of elderly mice. Dendritic morphology was evaluated with the Golgi-Cox staining procedure followed by the Sholl analysis. Bexarotene was administered at different doses: 0.0; 0.5; 2.5 and 5.0 mg/kg for 60 days in 18-month-old mice. After the treatment, locomotor activity in a novel environment and spatial memory in the water labyrinth were evaluated. Mice treated with bexarotene did not show significant changes in their behavior. Moreover, bexarotene-treated mice only showed a significant increase in the density of the dendritic spines and the dendritic length in the nucleus accumbens (NAcc) neurons. In conclusion, the administration of bexarotene improves the plasticity of the NAcc of aged mice, and therefore could be a pharmacological alternative to prevent or delay neuroplasticity disruptions in brain aging.

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

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.

Clozapine administration reverses behavioral, neuronal, and nitric oxide disturbances in the neonatal ventral hippocampus rat.

Clozapine is widely used in the treatment of schizophrenia; however its complete mechanism of action is not fully established. The neonatal ventral hippocampal lesion (nVHL) has emerged as a model of schizophrenia-related behavior. Our group has previously shown hyperresponsiveness to novel environment, neuronal atrophy in prefrontal cortex (PFC) and nucleus accumbens (NAcc) neurons as well as abnormal levels of nitric oxide (NO) in the PFC of the nVHL rat. In the present study, we aimed to investigate the role of repeated clozapine administration (2 mg/kg/day for 21 days) in a novel environment, neuronal rearrangement in PFC, NAcc and basolateral amygdala (BLA) as well as NO levels in this model. Clozapine administration reversed the hyperlocomotion observed in a novel environment in the nVHL rat with no effect on locomotion in sham animals. Quantitative morphological analysis demonstrated a retracted neuronal arborization and decreased spinogenesis in the NAcc, PFC and BLA in nVHL rat. Interestingly, clozapine administration also rescued neuronal atrophy in these brain regions. The nVHL also displayed increased NO levels in PFC, striatum and occipital cortex. Clozapine administration selectively reversed these abnormal levels of NO in striatum in nVHL rat while NO levels were increased in the PFC of sham animals. Our results further extend the usefulness of the nVHL as a model of schizophrenia-related behavior and suggest that clozapine reverses behavioral deficits in these animals by modulating neuronal reorganization and NO levels in the brain.

Maternal separation disrupts dendritic morphology of neurons in prefrontal cortex, hippocampus, and nucleus accumbens in male rat offspring.

Neonatal maternal separation (MS) in rats has widely been used as a neurodevelopmental model to mimic mood-related disorders. MS produces a wide array of behavioral deficits that persist throughout adulthood. In this study we investigate the effect of MS and substitute maternal handling (human handling) on the dendritic morphology of neurons in the prefrontal cortex (PFC), the CA1 ventral hippocampus, and the nucleus accumbens (NAcc), brain regions in male rats that have been associated with affective disorders at pre-pubertal (postnatal day 35 (PND35)) and post-pubertal (PND60) ages. The morphological characteristics of dendrites were studied by using the Golgi-Cox staining method. MS induced decreases in total dendritic length and dendritic spine density in the neurons of the PFC, the CA1 ventral hippocampus, and the NAcc at a post-pubertal age. Conversely, human handling produced an increase in dendritic spine density in the pyramidal neurons of the PFC and the hippocampus at a pre-pubertal age, and a decrease in the dendritic length of the NAcc neurons at a post-pubertal age. These results suggest that the maternal care condition affects the dendritic morphology of neurons in the PFC, the CA1 ventral hippocampus, and the NAcc at different ages. These anatomical modifications may be relevant to altered behaviors observed in maternally separated animals.