Neuroscience
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Comparative Study
Citalopram-mediated anxiolysis and differing neurobiological responses in both sexes of a genetic model of depression.
Disorders such as depression and anxiety exhibit strong sex differences in their prevalence and incidence, with women also differing from men in their response to antidepressants. Furthermore, receptors for corticotrophin releasing hormone (CRHR1) and arginine vasopressin receptor subtype 1b (AVPR1b) are known to contribute to the regulation of mood and anxiety. In the present study, we compared the anxiety profile and CRHR1 and AVPR1b expression levels in control Sprague-Dawley (SD) rats and rats of the SD-derived Flinders Sensitive Line (FSL), a genetic model of depression. ⋯ Importantly, whereas citalopram altered AVPR1b expression in the hypothalamus of male FSL rats, its actions on this parameter were restricted to the PFC in female FSL rats. In both sexes of FSL rats, citalopram did not alter CRHR1 expression in either the hypothalamus or PFC. Our results demonstrate that antidepressant treatment reduces anxiety levels in FSL rats of both sexes: the magnitude of treatment effect was related to the starting baseline level of anxiety and the antidepressant elicited sexually differentiated neurobiological responses in specific brain regions.
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Several lines of clinical evidence support the idea that fragile X syndrome (FXS) may involve a dysregulation of hypothalamic-pituitary-adrenal axis function [Wisbeck et al. (2000) J Dev Behav Pediatr 21:278-282; Hessl et al. (2002) Psychoneuroendocrinology 27:855-872]. We had tested this idea in a mouse model of FXS (Fmr1 KO) and found that the hormonal response to acute stress was similar to that of wild-type (WT) mice [Qin and Smith (2008) Psychoneuroendocrinology 33:883-889]. We report here responses to chronic stress (CS) in Fmr1 KO mice. ⋯ Similarly, spine density on apical and basal dendrites increased in WT but decreased in Fmr1 KO mice. Spine length on apical and basal dendrites increased in WT but was unaffected in Fmr1 KO mice. These differences in behavioral response and effects on neuron morphology in BLA suggest a diminished adaptive response of Fmr1 KO mice.
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Paclitaxel chemotherapy is limited by a long-lasting painful neuropathy that lacks an effective therapy. In this study, we tested the hypothesis that paclitaxel may release mast cell tryptase, which activates protease-activated receptor 2 (PAR2) and, subsequently, protein kinases A and C, resulting in mechanical and thermal (both heat and cold) hypersensitivity. Correlating with the development of neuropathy after repeated administration of paclitaxel, mast cell tryptase activity was found to be increased in the spinal cord, dorsal root ganglia, and peripheral tissues in mice. ⋯ Furthermore, sensitized pain response was selectively inhibited by antagonists of transient receptor potential (TRP) V1, TRPV4, or TRPA1. These results revealed specific cellular signaling pathways leading to paclitaxel-induced neuropathy, including the activation of PAR2 and downstream enzymes PLC, PKCε, and PKA and resultant sensitization of TRPV1, TRPV4, and TRPA1. Targeting one or more of these signaling molecules may present new opportunities for the treatment of paclitaxel-induced neuropathy.
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In the present study, the sources of thalamic and cortical inputs of thalamic reticular nucleus (TRN) neurons were examined by investigating the responses of the TRN neurons to electrical stimulation of different sites in the thalamus and the cortex of the rat. The recurrent excitation of the corticothalamic system that is triggered by electrical stimulation was eliminated by ablating the auditory cortex and by temporarily inactivating the medial geniculate body (MGB), when studying the sources of thalamic and cortical inputs, respectively. Single TRN neurons responded to electrical stimulation of 50-100 μA of the thalamus over a large area (dorsoventrally 1.2-2.4 mm and mediolaterally 1.0-2.3 mm, n=9). ⋯ The present study revealed that each TRN neuron received a wide range of inputs from both ascending thalamic and descending cortical projections. The projection could be cross-modal. Having a strong and lasting inhibition on the thalamus, the TRN neurons are likely to be involved in adjusting global states relating to awareness and attention in the thalamocortical system.
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Efficient encoding of sensory information can be implemented by heterogeneous response properties of neurons within sensory pathways. In the auditory system, neurons in the main auditory midbrain nucleus, the inferior colliculus (IC), show heterogeneous response properties to various types of acoustic stimuli including behaviorally relevant sounds. The receptive fields of these neurons, and their spatial organization, may reveal mechanisms that underlie response heterogeneity in the IC. ⋯ We found that the tonotopic progression is discontinuous in mouse IC, and we found that there is no clear spatial organization of frequency tuning curve types. Rather, there is heterogeneity of receptive fields in the bulk of the IC such that frequency tuning characteristics and hence the structure of excitatory and inhibitory inputs does not depend on location in the IC. This heterogeneity likely provides a mechanism for efficient encoding of auditory stimuli throughout the extent of the mouse IC.