8 research outputs found

    Sexually dimorphic long-term effects of an early life experience on AMPA receptor subunit expression in rat brain

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    Neonatal handling, an experimental model of early life experiences, is known to affect hypothalamic-pituitary-adrenal (HPA) axis function, thus increasing adaptability, coping with stress, cognitive abilities and in general brain plasticity-related processes. AMPA receptors (AMPARs) mediate fast synaptic transmission at excitatory glutamatergic synapses in the CNS and are crucial during neuronal development, synaptic plasticity and structural remodeling. AMPARs are composed of four types of subunits, designated as AMPA glutamate receptor subunits (GluA1, GluA2, GluA3 and GluA4), which combine to form tetramers. The present study addressed the question of whether neonatal handling (15. min daily maternal separation from postnatal day 1 (PND1) to PND21) might have an effect on GluA1-4 mRNA levels in adult rat male and female brain using in situ hybridization. We have identified selective sexually dimorphic effects of neonatal handling on the mRNA expression levels of AMPAR subunits in adult rat hippocampus and nuclei of the amygdaloid complex. In the dorsal hippocampus GluA1 mRNA levels were increased in handled males, while they were decreased in handled female animals. In the ventral hippocampus and the amygdaloid complex GluA2 mRNA was lower in handled females, while no effect was observed in handled males. Furthermore, we observed that neonatal handling induced in both sexes decreases of GluA2 mRNA in the dorsal hippocampus, as well as in the somatosensory and occipital cortex, of GluA3 mRNA in most hippocampal areas, amygdaloid complex and cortical regions studied, and of GluA4 mRNA in the ventral hippocampus. These results show that glutamatergic transmission is markedly affected by an early experience. The neonatal handling-induced alterations in AMPAR subunit composition are in line with the increased brain plasticity, the more effective HPA axis function, and in general the more adaptive behavioral phenotype known to characterize the handled animals. © 2013 IBRO

    Selective effects of neonatal handling on rat brain N-methyl-d-aspartate receptors

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    Neonatal handling, an experimental model of early life experiences, is known to affect the hypothalamic-pituitary-adrenal axis function thus increasing adaptability, coping with stress, cognitive abilities and in general brain plasticity-related processes. A molecule that plays a most critical role in such processes is the N-methyl-d-aspartate (NMDA) receptor, a tetramer consisting of two obligatory, channel forming NR1 subunits and two regulatory subunits, usually a combination of NR2A and NR2B. Since the subunit composition of the NMDA receptor affects brain plasticity, in the present study we investigated the effect of neonatal handling on NR1, NR2A and NR2B mRNA levels using in situ hybridization, and on NR2B binding sites, using autoradiography of in vitro binding of [3H]-ifenprodil, in adult rat limbic brain areas. We found that neonatal handling specifically increased NR2B mRNA and binding sites, while it had no effect on the NR1 and NR2A subunits. More specifically, neonatally handled animals, both males and females, had higher NR2B mRNA and binding sites in the dorsal CA1 hippocampal area, as well as the prelimbic, the anterior cingulate and the somatosensory cortex, compared to the non-handled. Moreover NR2B binding sites were increased in the dorsal CA3 area of handled animals of both sexes. Furthermore, neonatal handling had a sexually dimorphic effect, increasing NR2B mRNA and binding sites in the central and medial amygdaloid nuclei only of the females. The neonatal handling-induced increase in the NR2B subunit of the NMDA receptor could underlie the higher brain plasticity, which neonatally handled animals exhibit. © 2009 IBRO

    Expression of amino acid receptors and neural peptides in the weaver mouse brain

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    In the present study, we conducted: (i) in situ hybridization in order to investigate the expression of kainate and GABA(A) receptor subunits and the pre-proenkephalin and prodynorphin peptides in the brain of weaver mouse (a genetic model of dopamine deficiency) and (ii) immunocytochemistry in order to study the somatostatin-positive cells in weaver striatum. Our results indicated: (i) increases in mRNA levels of KA2 and GluR6 kainate receptor subunits, of alpha(4) and beta(3) GABA(A) receptor subunits and of pre-proenkephalin and prodynorphin in 6-month-old weaver striatum; (ii) a decrease in alpha(1) and beta(2) GABA(A) subunit mRNAs in 6-month-old weaver globus pallidus; (iii) increases in KA2, alpha(4) and beta(3) and decreases in alpha(2) and beta(2) mRNAs in the 6-month-old weaver somatosensory cortex; and (iv) an increase in somatostatin-immunopositive cells in 3-month-old weaver striatum. We suggest that: (i) in striatum, the alterations are induced by the induction of the transcription factor DeltafosB (for GluR6, pre-proenkephalin and prodynorphin mRNAs) and the suppression of transcription factors like NGF-IB (nerve growth factor inducible B; for the KA2 mRNA), in response to dopamine depletion; (ii) in striatum and cortex, the alterations in the expression of the GABA(A) subunits indicate an increase of extrasynaptic versus a decrease of synaptic GABA(A) receptors; and (iii) in globus pallidus, the increased striatopallidal GABAergic transmission leads to a decrease in the number of GABA(A) receptors. Our results further clarify the regulatory role of dopamine in the expression of amino acid receptors and striatal neuropeptides

    Effects of an early life experience on rat brain cannabinoid receptors in adolescence and adulthood

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    Neonatal handling is an experimental model of early life experience associated with resilience in later life challenges, altering the ability of animals to respond to stress. The endocannabinoid system of the brain modulates the neuroendocrine and behavioral effects of stress, while this system is also capable of being modulated by stress exposure itself. The present study has addressed the question of whether neonatal handling in rats could affect cannabinoid receptors, in an age- and sex-dependent manner, using in situ hybridization and receptor binding techniques. Different effects of neonatal handling were observed in adolescent and adult brain on CB1 receptor mRNA and [3H]CP55,940 binding levels, which in some cases were sexually dimorphic. Neonatal handling interfered in the developmental trajectories of CB1 receptor mRNA levels in striatum and amygdaloid nuclei, as well as of [3H]CP55,940 binding levels in almost all regions studied. Adult handled rats showed reduced [3H]CP55,940 binding levels in the prefrontal cortex, striatum, nucleus accumbens and basolateral amygdala, while binding levels in prefrontal cortex of adolescent handled rats were increased. Finally, handling resulted in decreases in female [3H]CP55,940 binding levels in the striatum, nucleus accumbens, CA3 and DG of dorsal hippocampus and basolateral amygdala. Our results suggest that a brief and repeated maternal separation during the neonatal period induces changes on cannabinoid receptors differently manifested between adolescence and adulthood, male and female brain, which could be correlated to their stress response. © 2018 The Author
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