The aim of the present study was to investigate the effects of individual housing on mouse behavior. The male mice of the C57BL/6J and DBA/2 strains were separated at the age of 4 weeks and kept in individual housing for 7 weeks until behavioral testing began. Their behavior was compared to the group-housed mice in a battery of tests during the following 7 weeks. The single-housed mice were hyperactive and displayed reduced habituation in the tests assessing activity and exploration. Reduced anxiety was established in the elevated plus-maze, but an opposite effect was observed in the dark-light (DL) and hyponeophagia tests. Immobility in the forced swimming test was reduced by social isolation. The DBA mice displayed higher anxiety-like behavior than the B6 mice in the plus-maze and DL exploration test, but hyponeophagia was reduced in the DBA mice. Moreover, all effects of individual housing on the exploratory and emotional behavior were more evident in the DBA than in the B6 mice. Novel object recognition and fear conditioning (FC) were significantly impaired in the single-housed mice, whereas water-maze (WM) learning was not affected. Marked strain differences were established in all three learning tests. The B6 mice performed better in the object recognition and FC tasks. Initial spatial learning in the WM was faster and memory retention slightly enhanced in the B6 mice. The DBA mice displayed lower preference to the new and enhanced preference to the old platform location than the B6 mice after reversal learning in the WM. We conclude that individual housing has strong strain- and test-specific effects on emotional behavior and impairs memory in certain tasks.

No abstract

Deficiency of the protein Wolfram syndrome 1 (WFS1) is associated with multiple neurological and psychiatric abnormalities similar to those observed in pathologies showing alterations in mitochondrial dynamics. The aim of this study was to examine the hypothesis that WFS1 deficiency affects neuronal function via mitochondrial abnormalities. We show that down-regulation of WFS1 in neurons leads to dramatic changes in mitochondrial dynamics (inhibited mitochondrial fusion, altered mitochondrial trafficking, and augmented mitophagy), delaying neuronal development. WFS1 deficiency induces endoplasmic reticulum (ER) stress, leading to inositol 1,4,5-trisphosphate receptor (IP3R) dysfunction and disturbed cytosolic Ca2+ homeostasis, which, in turn, alters mitochondrial dynamics. Importantly, ER stress, impaired Ca2+ homeostasis, altered mitochondrial dynamics, and delayed neuronal development are causatively related events because interventions at all these levels improved the downstream processes. Our data shed light on the mechanisms of neuronal abnormalities in Wolfram syndrome and point out potential therapeutic targets. This work may have broader implications for understanding the role of mitochondrial dynamics in neuropsychiatric diseases.

Five male triathletes of the Estonian national junior team were observed during a seven-week competition period. The Myoton-2 equipment was used to describe the viscoelastic parameters of the skeletal muscles. The frequency of damped mechanical oscillation of the muscle tissue (Hz - indicating the tension in the muscle), logarithmic decrement of the oscillations (Theta - indicating the elasticity of the muscle) and stiffness (N m(-1)) of the muscle tissue were registered bilaterally in eight muscles in both the relaxed and the contracted states: BB - biceps brachii (caput longum); TB - triceps brachii (caput longum); BF - biceps femoris (caput longum); RF - rectus femoris; TA - tibialis anterior; GC - gastrocnemius (caput mediale); LD - latissimus dorsi; PM - pectoralis major (pars sternocostalis). A portable massage table was used for the subject to rest on during the measuring. For the measurement of the anterior muscles, the subject lay supine; for the posterior muscles the prone position was used. The (isometric) contraction was standardized simply by the same measuring position of the limb-the subject raised his arm or leg to an angle of 45 degrees from the horizontal level, using a 2.3 kg dumb-bell as an additional weight for the upper limb. The tarsal dorsiflexion and plantarflexion was performed against a fixed table to contract the crural muscles. The elasticity of the skeletal muscle is higher for the contracted state with respect to the relaxed one (p < 0.0001) and is described by decline of the value of logarithmic decrement, the stiffness and the tension in the muscle increases (p < 0.0001 for both parameters). The measured skeletal muscles differ significantly (p < 0.0018) by the viscoelastic properties in the relaxed state. In the relaxed state, TA was the most elastic (mean +/- SD; Theta-0.74 +/- 0.13), stiff (mean +/- SD; 346.68 +/- 60.34 N m(-1)) and tense muscle (mean +/- SD; 18.72 +/- 1.55 Hz). In the contracted state, the elasticity of TA did not change (0.76 +/- 0.14) while the stiffness and the tension in this muscle rose significantly (93% and 38%, accordingly). Personal differences (p < 0.005) exist if pooled data from the muscles are compared between the subjects.

Mutations in the coding region of the WFS1 gene cause Wolfram syndrome, a rare multisystem neurodegenerative disorder of autosomal recessive inheritance. Patients with Wolfram syndrome display considerable clinical pleiomorphism, and symptoms such as neurological complications and psychiatric disorders are common. In the present study we have characterized Wfs1 expression pattern in the mouse central nervous system by using a combination of immunohistochemistry on wild-type mice and X-Gal staining of Wfs1 knockout mice with targeted insertion of the lacZ reporter. We identified a robust enrichment of Wfs1 protein in the central extended amygdala and ventral striatum. Prominent Wfs1 expression was seen in the hippocampal CA1 region, parasubiculum, superficial part of the second and third layers of the prefrontal cortex and proisocortical areas, hypothalamic magnocellular neurosecretory system, and central auditory pathway. Wfs1 expression was also detected in numerous brainstem nuclei and in laminae VIII and IX of the spinal cord. Wfs1-positive nerve fibers were found in the medial forebrain bundle, reticular part of the substantia nigra, globus pallidus, posterior caudate putamen, lateral lemniscus, alveus, fimbria, dorsal hippocampal commissure, subiculum, and to a lesser extent in the central sublenticular extended amygdala, compact part of substantia nigra, and ventral tegmental area. The neuroanatomical findings suggest that the lack of Wfs1 protein function can be related to several neurological and psychiatric symptoms found in Wolfram syndrome. Enrichment of Wfs1 protein in the central extended amygdala suggests a role in the modulation of anxiety and fear.