Papers by Karen S. Rommelfanger
Nature Reviews Neurology, 2013
Psychogenic movement disorders (PMDs) mimic known movement disorders but are not attributed to an... more Psychogenic movement disorders (PMDs) mimic known movement disorders but are not attributed to an underlying neurological pathology and are generally thought to have a psychological origin. Owing to the lack of a clear pathology, patients often experience multiple referrals, frequent office visits, and numerous-often fruitless-technically sophisticated tests and interventions. No standard of care exists for PMDs, and affected patients can experience debilitating symptoms for a lifetime. Some physicians advocate the use of placebo treatment for patients with PMDs, and placebo therapy can have beneficial neurophysiological effects. Innovative research will be necessary to develop effective therapeutics for psychogenic disorders and to make recommendations for future clinician training and health care policy. This Perspectives article aims to trigger international dialogue focusing on the diagnosis and treatment of patients with PMDs, and to reframe and deepen discussion of placebo prescribing for PMDs and beyond.
Biochem Pharmacol 74: 177-190, 2007
Journal of …, Jan 1, 2004
The noradrenergic neurons of the locus coeruleus (LC) are damaged in Parkinson's disease (PD). Ne... more The noradrenergic neurons of the locus coeruleus (LC) are damaged in Parkinson's disease (PD). Neurotoxin ablation of the LC noradrenergic neurons has been shown to exacerbate the dopaminergic toxicity of MPTP, suggesting that the noradrenergic system protects dopamine neurons. We utilized mice that exhibit elevated synaptic noradrenaline (NA) by genetically deleting the noradrenaline transporter (NET), a key regulator of the noradrenergic system (NET KO mice). NET KO and wild-type littermates were administered MPTP and striatal dopamine terminal integrity was assessed by HPLC of monoamines, immmunoblotting for dopaminergic markers and tyrosine hydroxylase (TH) immunohistochemistry. MPTP significantly reduced striatal dopamine in wild-type mice, but not in the NET KO mice. To confirm that the protection observed in the NET KO mice was due to the lack of NET, we treated wild-type mice with the specific NET inhibitor, nisoxetine, and then challenged them with MPTP. Nisoxetine conferred protection to the dopaminergic system. These data indicate that NA can modulate MPTP toxicity and suggest that manipulation of the noradrenergic system may have therapeutic value in PD.
Neuroscience, Jan 1, 2009
Electrophysiological and pharmacological studies have demonstrated that alpha-1 adrenergic recept... more Electrophysiological and pharmacological studies have demonstrated that alpha-1 adrenergic receptor (α1AR) activation facilitates dopamine (DA) transmission in the striatum and ventral midbrain. However, because little is known about the localization of α1ARs in dopaminergic regions, the substrate(s) and mechanism(s) underlying this facilitation of DA signaling are poorly understood. To address this issue, we used light and electron microscopy immunoperoxidase labeling to examine the cellular and ultrastructural distribution of α1ARs in the caudate putamen, nucleus accumbens, ventral tegmental area, and substantia nigra in the rat. Analysis at the light microscopic level revealed α1AR immunoreactivity mainly in neuropil, with occasional staining in cell bodies. At the electron microscopic level, α1AR immunoreactivity was found primarily in presynaptic elements, with scarce postsynaptic labeling. Unmyelinated axons and about 30–50% terminals forming asymmetric synapses contained the majority of presynaptic labeling in the striatum and midbrain, while in the midbrain a subset of terminals forming symmetric synapses also displayed immunoreactivity. Postsynaptic labeling was scarce in both striatal and ventral midbrain regions. On the other hand, only 3–6% of spines displayed α1AR immunoreactivity in the caudate putamen and nucleus accumbens,. These data suggest that the facilitation of dopaminergic transmission by α1ARs in the mesostriatal system is probably achieved primarily by pre-synaptic regulation of glutamate and GABA release.
Frontiers in Neuroanatomy, Jan 1, 2010
The basal ganglia are comprised of the striatum, the external and internal segment of the globus ... more The basal ganglia are comprised of the striatum, the external and internal segment of the globus pallidus (GPe and GPi, respectively), the subthalamic nucleus (STN), and the substantia nigra pars compacta and reticulata (SNc and SNr, respectively). Dopamine has long been identified as an important modulator of basal ganglia function in the striatum, and disturbances of striatal dopaminergic transmission have been implicated in diseases such as Parkinson's disease (PD), addiction and attention deficit hyperactivity disorder. However, recent evidence suggests that dopamine may also modulate basal ganglia function at sites outside of the striatum, and that changes in dopaminergic transmission at these sites may contribute to the symptoms of PD and other neuropsychiatric disorders. This review summarizes the current knowledge of the anatomy, functional effects and behavioral consequences of the dopaminergic innervation to the GPe, GPi, STN, and SNr. Further insights into the dopaminergic modulation of basal ganglia function at extrastriatal sites may provide us with opportunities to develop new and more specific strategies for treating disorders of basal ganglia dysfunction.
Abstract: Parkinson's disease (PD), which is characterized by the degeneration of dopami... more Abstract: Parkinson's disease (PD), which is characterized by the degeneration of dopamine (DA) neurons in the substantia nigra pars compacta (SNc), affects approximately 1% of the world's aging population. Because PD etiology is unknown, current therapies target the ...
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Papers by Karen S. Rommelfanger