Distribution and densitometry mapping of L1-CAM Immunoreactivity in the adult mouse brain – light microscopic observation

BACKGROUND: The importance of L1 expression in the matured brain is suggested by physiological and behavioral studies showing that L1 is related to hippocampal plasticity and fear conditioning. The distribution of L1 in mouse brain might provide a basis for understanding its role in the brain. RESULTS: We examined the overall distribution of L1 in the adult mouse brain by immunohistochemistry using two polyclonal antibodies against different epitopes for L1. Immunoreactive L1 was widely but unevenly distributed from the olfactory bulb to the upper cervical cord. The accumulation of immunoreactive L1 was greatest in a non-neuronal element of the major fibre bundles, i.e. the lateral olfactory tract, olfactory and temporal limb of the anterior commissure, corpus callosum, stria terminalis, globus pallidus, fornix, mammillothalamic tract, solitary tract, and spinal tract of the trigeminal nerve. High to highest levels of non-neuronal and neuronal L1 were found in the grey matter; i.e. the piriform and entorhinal cortices, hypothalamus, reticular part of the substantia nigra, periaqueductal grey, trigeminal spinal nucleus etc. High to moderate density of neuronal L1 was found in the olfactory bulb, layer V of the cerebral cortex, amygdala, pontine grey, superior colliculi, cerebellar cortex, solitary tract nucleus etc. Only low to lowest levels of neuronal L1 were found in the hippocampus, grey matter in the caudate-putamen, thalamus, cerebellar nuclei etc. CONCLUSION: L1 is widely and unevenly distributed in the matured mouse brain, where immunoreactivity was present not only in neuronal elements; axons, synapses and cell soma, but also in non-neuronal elements

Coincident Pre- and Postsynaptic Activation Induces Dendritic Filopodia via Neurotrypsin-Dependent Agrin Cleavage

SummaryThe synaptic serine protease neurotrypsin is essential for cognitive function, as its deficiency in humans results in severe mental retardation. Recently, we demonstrated the activity-dependent release of neurotrypsin from presynaptic terminals and proteolytical cleavage of agrin at the synapse. Here we show that the activity-dependent formation of dendritic filopodia is abolished in hippocampal neurons from neurotrypsin-deficient mice. Administration of the neurotrypsin-dependent 22 kDa fragment of agrin rescues the filopodial response. Detailed analyses indicated that presynaptic action potential firing is necessary for the release of neurotrypsin, whereas postsynaptic NMDA receptor activation is necessary for the neurotrypsin-dependent cleavage of agrin. This contingency characterizes the neurotrypsin-agrin system as a coincidence detector of pre- and postsynaptic activation. As the resulting dendritic filopodia are thought to represent precursors of synapses, the neurotrypsin-dependent cleavage of agrin at the synapse may be instrumental for a Hebbian organization and remodeling of synaptic circuits in the CNS

Authentic role of ATP signaling in micturition reflex

Adenosine triphosphate (ATP) is a signaling molecule that regulates cellular processes. Based on previous studies of bladder function over the past decade, bladder ATP signaling was thought to have an essential role in the normal micturition reflex. In this study, we performed detailed analyses of bladder function in purinergic receptor-deficient mice using the automated voided stain on paper method and video-urodynamics. Unexpectedly, a lack of P2X2 or P2X3 receptors did not affect bladder function under normal physiological conditions, indicating that bladder ATP signaling is not essential for normal micturition reflex. In contrast, we found that lipopolysaccharide (LPS) induced markedly high levels of ATP release from the urothelium. In addition, LPS-induced rapid bladder hyperactivity was attenuated in P2X2 -/- and P2X3 -/- mice. Contrary to the previous interpretation, our present findings indicate that bladder ATP signaling has a fundamental role in the micturition reflex, especially in bladder dysfunction, under pathological conditions. Therefore, the bladder ATP signaling pathway might be a highly promising therapeutic target for functional bladder disorders. This study newly defines an authentic role for bladder ATP signaling in the micturition reflex

Activity-controlled proteolytic cleavage at the synapse

Activity-controlled enzymatic cleavage of proteins on the surface of synaptic membranes or in the synaptic or perisynaptic interstitial compartment represents a direct way to regulate synaptic structure, function, and number. Extracellular proteolysis at synapses was initially understood to be plasticity enabling by freeing synapses from the constraints provided by the extracellular matrix. However, recent observations indicate that at least part of the extracellular protein cleavage results in activation of previously cryptic functions that regulate adaptive changes of synapses and neuronal circuits. Here, we focus on peptidases with distinct localization and function at synapses combined with regulation by neuronal and synaptic activity, and evaluate their function in the context of developmental and/or adult synaptic plasticity

LBX1 mRNA Expression in Paravertebral Muscles of Patients with Adolescent Idiopathic Scoliosis : a Preliminary Study

Objectives : To investigate LBX1 mRNA expression in bilateral paravertebral muscles in adolescent idiopathic scoliosis (AIS) and control subjects to clarify its association with development and progression of scoliosis. Summary of background data : Paravertebral muscle abnormalities in AIS patients have been investigated through various methods. Despite the roles of LBX1 in skeletal muscles, the association with idiopathic scoliosis is still unclear. Methods : Fourteen AIS patients (average age, 15.9±2.2 years ; average Cobb angle, 48.2±8.9°) and 7 controls (average age, 26.4±9.7 years) were included. Muscle samples were harvested from bilateral paravertebral muscles at the apical vertebral level. LBX1 mRNA expression was evaluated by the real-time PCR. LBX1 expressions in bilateral paravertebral muscles were compared in each group. The expression ratio, the expression at the convex side relative to the concave side, was compared between groups. Correlation between expression ratio and Cobb angle was analyzed. Results : LBX1 expression on the convex side was higher than that on the concave side in AIS group (p=0.020), and the expression ratio of LBX1 in the AIS group was higher than that of controls (p=0.012). However, there was no significant correlation between the expression ratio of LBX1 and Cobb angle (r=－0.3826, p=0.177). Conclusions : In the AIS group, LBX1 mRNA expression was asymmetric. The AIS group had higher expression ratios than the controls. These findings suggest the possible functional role of paravertebral muscles in the development or progression of the spinal curve