Repeated stress induces dendritic spine loss in the rat medial prefrontal cortex

Department of Neuroscience, Mount Sinai School of Medicine, New York, NY 10029, USA.
Cerebral Cortex (Impact Factor: 8.67). 04/2006; 16(3):313-20. DOI: 10.1093/cercor/bhi104
Source: PubMed

ABSTRACT The prefrontal cortex (PFC) plays an important role in higher cognitive processes, and in the regulation of stress-induced hypothalamic-pituitary-adrenal (HPA) activity. Here we examined the effect of repeated restraint stress on dendritic spine number in the medial PFC. Rats were perfused after receiving 21 days of daily restraint stress, and intracellular iontophoretic injections of Lucifer Yellow were carried out in layer II/III pyramidal neurons in the anterior cingulate and prelimbic cortices. We found that stress results in a significant (16%) decrease in apical dendritic spine density in medial PFC pyramidal neurons, and confirmed a previous observation that total apical dendritic length is reduced by 20% in the same neurons. We estimate that nearly one-third of all axospinous synapses on apical dendrites of pyramidal neurons in medial PFC are lost following repeated stress. A decrease in medial PFC dendritic spines may not only be indicative of a decrease in the total population of axospinous synapses, but may impair these neurons' capacity for biochemical compartmentalization and plasticity in which dendritic spines play a major role. Dendritic atrophy and spine loss may be important cellular features of stress-related psychiatric disorders where the PFC is functionally impaired.

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Available from: Jason J Radley, Oct 01, 2014
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    • "The medial prefrontal cortex (MPFC) plays an important role in the modulation of behavioural and physiological responses to stressful stimuli. Several studies demonstrated MPFC remodelling following chronic exposure to stressors, and these cellular changes could be implicated in psychiatric disorders (Radley et al. 2004, 2006b, 2008). The ventral portion of the MPFC is comprised of the prelimbic (PL), infralimbic (IL) and dorsal peduncular cortices (Zilles & Wree, 1985; Paxinos & Watson, 2007). "
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    ABSTRACT: The infralimbic cortex (IL) is known to modulate behavioral and physiological responses during aversive situations. We investigated the hypothesis that an IL opioid neurotransmission modulates the autonomic responses induced in rats subjected to restraint stress (RS). Male Wistar rats (250-280 g) were used. Guide cannulae were implanted bilaterally in the IL for the microinjection of either drugs or vehicle, and a polyethylene catheter was implanted into the femoral artery for mean arterial pressure (MAP) and heart rate (HR) recording using a computerized acquisition system. Tail temperature was evaluated using a thermal camera. Rats were subjected to RS 10 min after the microinjection of drugs or vehicle into the IL. Exposure to RS evoked hypertension, tachycardia and fall in tail temperature. Bilateral microinjections of the nonselective opioid antagonist naloxone into the IL generated an inverted U-shaped dose-inhibition curve on RS-evoked MAP and HR responses. Microinjection of nor-BNI (κ-selective antagonist) reduced the increases in MAP and HR evoked by RS. On the other hand, the IL pretreatment with CTAP (μ-selective antagonist) or naltrindole (δ-selective antagonist) had no effect on the restraint-evoked MAP and HR increases. None of these treatments altered the fall in the tail temperature evoked by RS. In conclusion, κ-opioid receptors in the IL modulate pressor and tachycardiac responses caused by RS, suggesting a facilitatory role of this structure in this aversive situation.This article is protected by copyright. All rights reserved
    Experimental physiology 01/2015; 100(4). DOI:10.1113/expphysiol.2014.084020 · 2.87 Impact Factor
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    • "Se encontraron dos resultados distintos. Por un lado, se encontró una reducción en la cantidad de espinas dendríticas presentes en las neuronas en mCPF y, por otro lado, un aumento en el número de ramificaciones dendríticas y de nuevas espinas dendríticas en OFC (Liston et al., 2006; Radley et al., 2006). Los cambios en las conexiones sinápticas generados en estas áreas se acompañaron de disminución en las funciones ejecutivas, tales como déficit en la toma de decisiones, baja autorregulación emocional y disminución en la focalización de la atención. "
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    • "Several limbic brain regions, including prefrontal cortex, hippocampus, amygdala, and nucleus accumbens (NAc), have been implicated in mediating key symptoms of depression and anxiety (Keedwell et al., 2005; Krishnan and Nestler, 2008; Mayberg et al., 2005). Chronic exposure to physical or psychological stress impairs the structure and function of neurons in prefrontal cortex (Radley et al., 2006), hippocampus (Surget et al., 2011) and amygdala (Mozhui et al., 2010). These changes depend on de novo synthesis of proteins involved in neural and synaptic plasticity. "
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