The development of compulsive coping behaviour is associated with a downregulation of Arc in a Locus Coeruleus neuronal ensemble

Some compulsive disorders have been considered to stem from the loss of control over coping strategies, such as displacement. However, the cellular mechanisms involved in the acquisition of coping behaviours and their subsequent compulsive manifestation in vulnerable individuals have not been elucidated. Considering the role of the locus coeruleus (LC) noradrenaline-dependent system in stress and related excessive behaviours, we hypothesised that neuroplastic changes in the LC may be associated with the acquisition of an adjunctive polydipsic water drinking, a prototypical displacement behaviour, and the ensuing development of compulsion in vulnerable individuals. Thus, male Sprague Dawley rats were characterised for their tendency, or not, to develop compulsive polydipsic drinking in a schedule-induced polydipsia (SIP) procedure before their fresh brains were harvested. A new quantification tool for RNAscope assays revealed that the development of compulsive adjunctive behaviour was associated with a low mRNA copy number of the plasticity marker Arc in the LC which appeared to be driven by specific adaptations in an ensemble of tyrosine hydroxylase (TH)+, zif268− neurons. This ensemble was specifically engaged by the expression of compulsive adjunctive behaviour, not by stress, because its functional recruitment was not observed in individuals that no longer had access to the water bottle before sacrifice, while it consistently correlated with the levels of polydipsic water drinking only when it had become compulsive. Together these findings suggest that downregulation of Arc mRNA levels in a population of a TH+/zif268− LC neurons represents a signature of the tendency to develop compulsive coping behaviours.Subject terms: Stress and resilience, Cellular neuroscience     

Cortical Processing of Complex Auditory Stimuli during Alterations of Consciousness with the General Anesthetic Propofol

Background: The extent to which complex auditory stimuli are processed and differentiated during general anesthesia is unknown. The authors used blood oxygenation level-dependent functional magnetic resonance imaging to examine the processing words (10 per period; compared with scrambled words) and nonspeech human vocal sounds (10 per period; compared with environmental sounds) during propofol anesthesia.

Methods: Seven healthy subjects were tested. Propofol was given by a computer-controlled pump to obtain stable plasma concentrations. Data were acquired during awake baseline, sedation (propofol concentration in arterial plasma: 0.64 +/- 0.13 [mu]g/ml; mean +/- SD), general anesthesia (4.62 +/- 0.57 [mu]g/ml), and recovery. Subjects were asked to memorize the words.

Results: During all periods including anesthesia, the sounds conditions combined elicited significantly greater activations than silence bilaterally in primary auditory cortices (Heschl gyrus) and adjacent regions within the planum temporale. During sedation and anesthesia, however, the magnitude of the activations was reduced by 40-50% (P < 0.05). Furthermore, anesthesia abolished voice-specific activations seen bilaterally in the superior temporal sulcus during the other periods as well as word-specific activations bilaterally in the Heschl gyrus, planum temporale, and superior temporal gyrus. However, scrambled words paradoxically elicited significantly more activation than normal words bilaterally in planum temporale during anesthesia. Recognition the next day occurred only for words presented during baseline plus recovery and was correlated (P < 0.01) with activity in right and left planum temporale.     

Comparison of single-breath-hold fast spin-echo sequences with routine non-breath-hold techniques: Application to MRI of renal masses

In 24 patients presenting with 55 renal lesions (mean size, 20.8 mm), single-breath-hold (SBH) fast spin-echo (FSE) techniques allowing T1 and T2 images to be produced within 20 and 23 sec, respectively, were compared with routine non-breath-hold (NBH) spin-echo (SE) T1 and NBH-FSE T2 sequences. Contrast-to-noise ratios (CNRs) measured from SBH-FSE T1 images were an average of 97% higher than their NBH counterparts (P = .0001) and allowed an improved lesion conspicuity in 80% of the cases (P = .0001). For T2 imaging, SBH-FSE and NBH-FSE sequences were not statistically different with respect to lesion conspicuity (P = .55) and CNR values (P = .19). This was observed despite a 35% average decrease in CNR of SBH-FSE compared to NBH-FSE images. By reducing respiratory motion artifacts while preserving SE-like image contrast, SBH-FSE techniques have the potential to replace routine NBH sequences for an optimal diagnosis of renal masses.     

Induction of MMP9 (92 kDa Gelatinase) Activity and Expression of Tissue In hibitor of Metalloproteinase-2 mRNA (TIMP-2) in Primitive Neuroectodermal Cells Infected with Retrovirus HTLV-I

Matrix-degrading proteases, including metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs), are involved in modulation of the extracellular matrix, which participates in neural cell differentiation, brain morphogenesis and tissue integrity. Metalloproteinases and TlMPs are associated with inflammatory and degenerative processes in the central nervous system and are regulated by cytokines. Human retroviral infections are frequently associated with neurological disturbances. In the present paper, we have studied the changes occurring in human primitive neuroectodermal cells following infection with human T cell lymphotropic virus type 1 (HTLV-I), a retrovirus responsible for HTLV-I-associated myelopathy. Infected neural cells were found to have high metalloproteinase 9 (MMP9–92 kDa gelatinase) activity. MMP9 induction is dependent on HTLV-I infection of neural cells. In addition, soluble factors, especially tumour necrosis factor α, secreted by infected cells, act as mediators of induction. HTLV-I infection also induces expression of RNA coding for tissue inhibitor of metalloproteinase 2. These observations indicate that HTLV-I infection selectively modulates the expression of molecules involved in the dynamic equilibrium between the synthesis and degradation of the neural cell matrix and leads to its remodelling, which modifies cell-cell interactions and cellular function.     

Inhibition of complement-dependent rosette formation after lymphocyte incubation with fatty acids.

Overnight incubation of lymphocytes with certain fatty acids bound to albumin has previously been shown to modify the fatty acid composition of cellular phosphoglycerides without impairing viability, and also to inhibit mitogen and antigen-induced lymphocyte transformation. In the present study, incubation of human lymphocytes with palmitic acid or with linoleic acid impaired their capacity to form complement-dependent rosettes but had no effect on either spontaneous rosette formation with sheep erythrocytes or Fc(gamma)-dependent rosette formation. With mouse lymphocytes, complement-dependent rosette formation was suppressed only following incubation with linoleic acid and there was no effect on Fc(gamma)-dependent rosette formation. Although the mechanism of these effects remains to be elucidated the results suggest that control of membrane lipid composition may modify the important in vivo immunological functions which involve complement receptors.