Elsevier

Brain Research

Volume 983, Issues 1–2, 5 September 2003, Pages 128-136
Brain Research

Research report
Decreased dendritic spine density on prefrontal cortical and hippocampal pyramidal neurons in postweaning social isolation rats

https://doi.org/10.1016/S0006-8993(03)03042-7Get rights and content

Abstract

The effects of postweaning social isolation (pwSI) on the morphology of the pyramidal neurons from the medial part of the prefrontal cortex (mPFC) and hippocampus were investigated in rats. The animals were weaned on day 21 postnatal (P21) and isolated 8 weeks. After the isolation period, locomotor activity was evaluated through 60 min in the locomotor activity chambers and the animals were sacrificed by overdoses of sodium pentobarbital and perfused intracardially with 0.9% saline solution. The brains were removed, processed by the Golgi-Cox stain and analyzed by the Sholl method. The locomotor activity in the novel environment from the isolated rats was increased with respect to the controls. The dendritic morphology clearly showed that the pwSI animals presented a decrease in dendritic length of pyramidal cells from the CA1 of the hippocampus without changes in the pyramidal neurons of the mPFC. However, the density of dendritic spines was decreased in the pyramidal cells from mPFC and Hippocampus. In addition, the Sholl analyses showed that pwSI produced a decrease in the number of sholl intersections compared with the control group only in the hippocampus region. The present results suggest that pwSI may in part affect the dendritic morphology in the limbic structures such as mPFC and hippocampus that are implicated in schizophrenia.

Introduction

Rat animals live in social groups, pre-pubertal and pubertal steps are critical to establish social organization in a group. During these periods, young rats spent much of the time in social play behavior [28]. The occurrence of social play follows an inverted U-shape during their development. It emerges at about 18 days postnatally (P18), giving peaks during P28 to P35 and decreases with age until sexual maturity [2], [37], [58]. The social play is crucial for establishing social organization in a group [59]. In addition, social isolation produces a well characterized syndrome consisting in hyperactivity, such as increased locomotor activity in response to a novel environment and dopamine (DA) agonist [25], [33], decreased pain thresholds [44], deficit in the prepulse inhibition [11], [19], [61], [64], [65] and altered response to neuroleptic drugs [50]. These behavioral effects implicate alterations in DA function, in particular, in the DAergic mesolimbic system [19], [25], [33], [64]. In addition, in vivo microdialysis data has revealed that social isolation produces an increase in the DA levels in caudate-putamen and nucleus accumbens [33].

Social dysfunction has been implicated in the development and course of schizophrenia [1]. Before schizophrenic symptoms initiate, the patients tends to social isolation; however, when the schizophrenic symptoms appear, the social isolation is exacerbated [3], [26], [31], [62]. The medial part of the prefrontal cortex (mPFC) and hippocampus (Hc) appear to be critical sites of dysfunction in schizophrenic patients [40], [63]. Recent data have shown a decrease in the dendritic spine density on the hippocampus and the medial part of the prefrontal cortical pyramidal neurons in subjects with schizophrenia [21]. Furthermore, evidence has been accumulated which implicates cortical neuronal error in the development in schizophrenia [63]. Studies on mPFC or ventral Hc lesions [4], [5], [6], [14], [15], [36] induced in the neonatal rat brain indicated that these regions might be have participated in the development of subcortical dopaminergic activity. In addition, schizophrenic symptoms appear in adolescence or early adulthood, after the social play period. Given the importance of social functioning in schizophrenia, it is critical to understand factors with underlie deficits in this area. The postweaning social isolation (pwSI) model has been related with the schizophrenia [17], [18], [55].

In the present investigation, we have compared the developmental consequence of pwSI in rats 8 weeks after being weaned. At adult ages, dendritic longitude and spine density on pyramidal neurons from mPFC and Hc were evaluated in pwSI rats and controls. The results suggest an important role of the pwSI on the development and maturation of the mPFC and Hc pyramidal neurons in adult rats.

Section snippets

Material and methods

Male Sprague–Dawley rats used in this study were obtained and bred in our animal facilities (University of Puebla). On day 21 postnatal (P21) the animals were weaned and were randomly divided into two rearing conditions: nine rats were reared in isolation during 8 weeks and a similar number in social groups. Isolation-reared rats were housed individually in cages (45×20×20-cm high). While socially reared rats were housed three at a time in similar cages. All subjects were housed in the same

Locomotor activity

The effects of the pwSI on locomotor activity in a novel environment are illustrated in Fig. 3. Both, control or social isolation animals exhibited active exploratory behaviour when placed in a novel environment. A significant increase in the locomotor behaviour was clearly observed in the pwSI animals group (P=0.02), when compared with the control group (Fig. 3b).

Golgi-Cox staining

Dendritic branching and density of dendritic spines on neuron from mPFC and Hc were measured by Golgi-Cox stain between pwSI and

Discussion

The major aim of the present study was to investigate the consequences of 8 weeks of social isolation immediately introduced after weaning (P21) on the basilar dendritic structural morphology from layer 3 pyramidal cells of the prefrontal cortex and pyramidal neurons from the CA1 region of the hippocampus. We report here that the pwSI induces major reductions in dendritic spine density in layer 3 pyramidal neurons from the mPFC and pyramidal neurons from the Hc, these data may be linked in part

Acknowledgements

This study was supported in part by grants from CONACyT-Mexico (No. 40664) and VIEP-BUAP (No. IV19I02). We are grateful to Dr. Carlos Escamilla for his help and suggestions related to keeping of animals. We thank Dr. Fernando Peralta for correcting the manuscript. ABS-G has a studentship from ESM-IPN and DR has a studentship from BUAP. GF is a member of the Researcher National System of Mexico.

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