Formation Of Supernumerary Muscle Spindles At The Expense Of Golgi Tendon Organs In Er81-deficient Mice
Anatomy & Morphology; Developmental Biology; ETS transcription factors; expression; Golgi tendon organs; group; ia afferents; innervation; motor neurons; muscle spindles; mutant mice; myosin heavy-chain; neonatal rats; nerve growth-factor; neurotrophin-3; primary sensory neurons; proprioceptive afferents; transcription factors
ER81, a member of the ETS family of transcription factors, is essential for the formation of connections between sensory and motor neurons in the spinal cord. Mice lacking Er81 genes exhibit reduced monosynaptic sensory-motoneuron connectivity in response to muscle nerve stimulation. Proximal muscle nerve stimulation elicits fewer monosynaptic potentials than stimulation of distal nerves in hind-limbs, a deficit that is paralleled by a paucity of muscle spindles in proximal muscles (Arber et al., 2000). We examined whether a presence of spindles innervated by afferents in distal muscles correlated with the increased preservation of monosynaptic sensory-motor potentials in distal muscle nerves. Not only were spindles and Ia afferents present, but also they were supernumerary in distal muscles such as the soleus, medial gastrocnemius, and extensor hallucis longus. Concomitantly, a deficiency of Golgi tendon organs (GTOs) and Ib afferents was observed in distal muscles, as if supernumerary spindles formed at the expense of tendon organs in the absence of Er81. Thus, ER81 may be involved in mechanisms that regulate acquisition of the Ia and Ib phenotypes by subsets of proprioceptive muscle afferents. Segmental differences in muscle spindle and GTO dependence on ER81 suggest that more than one ETS transcription factor may participate in the regulation of limb proprioceptive system assembly in the mouse. (C) 2002 Wiley-Liss, Inc.
Kucera J; Cooney W; Que A; Szeder V; Stancz-Szeder H; Walro J
Developmental Dynamics
2002
2002-03
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1002/dvdy.10066" target="_blank" rel="noreferrer noopener">10.1002/dvdy.10066</a>
Metabolic And Transmitter Changes In Core And Penumbra After Middle Cerebral Artery Occlusion In Mice
acetylcholine; Choline; focal ischemia; Glucose; glutamate; glutamate; Glycerol; hippocampus; hippocampus; intracerebral microdialysis; Microdialysis; mutant mice; neurodegenerative disorders; Neurosciences & Neurology; rat; release; reperfusion; Striatum; stroke
Middle cerebral artery occlusion (MCAO) is a popular model in experimental stroke research and causes prominent ischemic damage in the forebrain. To characterize metabolic changes induced by MCAO, we have induced permanent MCAO in mice that were implanted with a microdialysis probe in either striatum or hippocampus. Immediately after the onset of ischemia, glucose levels dropped to <10% of basal values in the striatum while they dropped to 50%, and recovered thereafter, in hippocampus. Extracellular levels of glutamate rose 80-fold in the striatum but only 10-fold, and in a transient fashion, in hippocampus. In striatum, release of acetylcholine briefly increased, then dropped to very low values. Both glycerol and choline levels increased strongly during ischemia in the striatum reflecting membrane breakdown. In hippocampus, glycerol increased transiently while the increase of choline levels was moderate. Taken together, these observations delineate metabolic changes in ischemic mouse brain with the striatum representing the core area of ischemia. In comparison, the dorsal hippocampus was identified as a brain area suitable for monitoring metabolic responses in the penumbra region. (C) 2009 Elsevier B.V. All rights reserved.
Kiewert C; Mdzinarishvili A; Hartmann J; Bickel U; Klein J
Brain Research
2010
2010-02
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1016/j.brainres.2009.11.068" target="_blank" rel="noreferrer noopener">10.1016/j.brainres.2009.11.068</a>
Methamphetamine-induced Loss Of Striatal Dopamine Innervation In Bdnf Heterozygote Mice Does Not Further Reduce D-3 Receptor Concentrations
1-methyl-4-phenyl-1; 2; 3; 6-tetrahydropyridine mptp; behavioral; caudate putamen; differential regulation; dopamine; haloperidol treatment; monkey; motor neurons; mutant mice; Neurosciences & Neurology; neurotrophic factor; nucleus accumbens; parkinsons-disease; parkinsons-disease; sensitization; Striatum; substantia-nigra; transporter; tyrosine hydroxylase
Depletion of dopamine (DA) reduces D, receptor number, but D-3 receptor expression is also regulated by brain-derived neurotrophic factor (BDNF). We took advantage of transgenic heterozygous BDNF mutant mice (+/-) to determine if reduced BDNF and loss of DA fibers produced by methamphetamine were additive in their impact on D-3 receptor number. We assessed selective markers of the dopaminergic system including caudate-putamen DA concentrations and quantitative autoradiographic measurement of tyrosine hydroxylase (TH) levels, DA transporter (DAT), and DA D-3 receptor binding between vehicle and methamphetamine-treated BDNF +/- and their wildtype (WT) littermate control mice. Caudate-putamen DA concentrations, TH and DAT levels were significantly reduced following methamphetamine treatment in both WT and BDNF +/- mice. The extent of methamphetamine-induced reduction in TH and DAT was greater for the WT than BDNF +/- mice and DAT levels were also decreased to a greater extent in nucleus accumbens of WT as compared to BDNF +/- mice. Lower D-3 receptor existed in caudate-putamen and nucleus accumbens in BDNF +/- mice and these differences were not affected by methamphetamine treatment. Taken together, these results not only substantiate the importance of BDNF in controlling D-3 receptor expression, but also indicate that a methamphetamine-induced depletion of DA fibers fails to produce an additive effect with lowered BDNF for control of D-3 receptor expression. In addition, the reduction of D-3 receptor expression is associated with a decreased neurotoxic response to methamphetamine in BDNF +/- mice. (C) 2004 Wiley-Liss, Inc.
Joyce J N; Renish L; Osredkar T; Walro J M; Kucera J; Dluzen D E
Synapse
2004
2004-04
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1002/syn.10309" target="_blank" rel="noreferrer noopener">10.1002/syn.10309</a>
Neurotrophin-3 Ameliorates Sensory-motor Deficits In Er81-deficient Mice
afferents; Anatomy & Morphology; connections; Developmental Biology; differentiation; ER81; ETS; innervation; motor neurons; muscle spindles; muscle spindles; mutant mice; neurons; neurotrophins; NT3; rat; regeneration; sensory neurons; specification; spinal-cord; transcription factors
Two factors, the ETS transcription factor ER81 and skeletal muscle-derived neurotrophin-3 (NT3), are essential for the formation of muscle spindles and the function of spindle afferent-motoneuron synapses in the spinal cord. Spindles either degenerate completely or are abnormal, and spindle afferents fail to project to spinal motoneurons in Er81 null mice; however, the interactions between ER81 and NT3 during the processes of afferent neuron and muscle spindle development are poorly understood. To examine if overexpression of NT3 in muscle rescues spindles and afferent-motoneuron connectivity in the absence of ER81, we generated myoNT3;Er81(-/-) double-mutant mice that selectively overexpress NT3 in muscle in the absence of ER81. Spindle reflex arcs in myoNT3;Er81(-/-) mutants differed greatly from Er81 null mice. Muscle spindle densities were greater and more afferents projected into the ventral spinal cord in myoNT3;Er81(-/-) mice. Spindles of myoNT3,Er81(-/-) muscles responded normally to repetitive muscle taps, and the monosynaptic inputs from la afferents to motoneurons, grossly reduced in Er81(-/-) mutants, were restored to wild-type levels in myoNT3,Er81(-/-) mice. Thus, an excess of muscle-derived NT3 reverses deficits in spindle numbers and afferent function induced by the absence of ER81. We conclude that muscle-derived NT3 can modulate spindle density and afferent-motoneuron connectivity independently of ER81.
Li L Y; Wang Z; Sedy J; Quazi R; Walro J M; Frank E; Kucera J
Developmental Dynamics
2006
2006-11
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1002/dvdy.20964" target="_blank" rel="noreferrer noopener">10.1002/dvdy.20964</a>