Deep brain stimulation of the posterior hypothalamic nucleus reverses akinesia in bilaterally 6-hydroxydopamine—lesioned rats

Deep brain stimulation (DBS) of the basal ganglia motor circuitry is a highly effective treatment for the debilitating motor symptoms of Parkinson's disease (PD). However, recent findings have indicated promising potential for PD therapy with DBS in brain structures outside the basal ganglia. For example, high frequency stimulation of the posterior hypothalamic nucleus (PH) can reverse haloperidol-induced akinesia in rats [Jackson J, Young CK, Hu B, Bland BH (2008) High frequency stimulation of the posterior hypothalamic nucleus restores movement and reinstates hippocampal-striatal theta coherence following haloperidol-induced catalepsy. Exp Neurol 213:210-219]. In the current study, we used the bilateral 6-hydroxydopamine lesion model of Parkinsonian akinesia in male Long-Evans rats to further explore the efficacy of PH DBS. The application of PH DBS in lesioned animals reversed akinesia in an active avoidance paradigm with increased latency compared to pre-lesion performance. The dramatic reversal of akinesia in two models of rodent Parkinsonism by PH DBS warrants further exploration of its therapeutic potential.

[1]  Y. Mayanagi,et al.  Posteromedial hypothalamotomy in the treatment of violent, aggressive behaviour. , 1988, Acta neurochirurgica. Supplementum.

[2]  G. Broggi,et al.  Deep brain stimulation and cluster headache , 2005, Neurological Sciences.

[3]  A. Benabid,et al.  Five-year follow-up of bilateral stimulation of the subthalamic nucleus in advanced Parkinson's disease. , 2003, The New England journal of medicine.

[4]  K. Sano,et al.  Posteromedial Hypothalamotomy in the treatment of tractable pain,. , 1975, Confinia neurologica.

[5]  M. Merello,et al.  Deep Brain Stimulation of the Subthalamic Nucleus for the Treatment of Parkinson's Disease , 2008 .

[6]  Li-Hong Shi,et al.  Studies of the neural mechanisms of deep brain stimulation in rodent models of Parkinson's disease , 2008, Neuroscience & Biobehavioral Reviews.

[7]  Ying Liu,et al.  High frequency deep brain stimulation: What are the therapeutic mechanisms? , 2008, Neuroscience & Biobehavioral Reviews.

[8]  Matthias H. J. Munk,et al.  Information Processing by Neuronal Populations , 2008 .

[9]  G. Iwamoto,et al.  Microinjection of GABA antagonists into the posterior hypothalamus elicits locomotor activity and a cardiorespiratory activation , 1988, Brain Research.

[10]  Zelma H T Kiss,et al.  Selective Attenuation of Afferent Synaptic Transmission as a Mechanism of Thalamic Deep Brain Stimulation-Induced Tremor Arrest , 2006, The Journal of Neuroscience.

[11]  B H Bland,et al.  Diencephalic and hippocampal mechanisms of motor activity in the rat: effects of posterior hypothalamic stimulation on behavior and hippocampal slow wave activity. , 1972, Brain research.

[12]  Y. Mayanagi,et al.  Autonomic, somatomotor and electroencephalographic responses upon stimulation of the hypothalamus and the rostral brain stem in man. , 1967, Confinia neurologica.

[13]  Massimo Leone,et al.  Deep brain stimulation in headache , 2006, The Lancet Neurology.

[14]  R. Rivest,et al.  Hypokinesia, rigidity, and tremor induced by hypothalamic 6-OHDA lesions in the rat , 1991, Brain Research Bulletin.

[15]  H. M. Sinnamon,et al.  Locomotor stepping initiated by glutamate injections into the hypothalamus of the anesthetized rat. , 1990, Behavioral neuroscience.

[16]  Bin Hu,et al.  High frequency stimulation of the posterior hypothalamic nucleus restores movement and reinstates hippocampal–striatal theta coherence following haloperidol-induced catalepsy , 2008, Experimental Neurology.

[17]  C. Ohye,et al.  Postero-medial hypothalamotomy in the treatment of aggressive behaviors. , 1966, Confinia neurologica.

[18]  R. Vertes,et al.  Descending projections of the posterior nucleus of the hypothalamus: Phaseolus vulgaris leucoagglutinin analysis in the rat , 1996, The Journal of comparative neurology.

[19]  P. Stanzione,et al.  Bilateral deep brain stimulation of the pedunculopontine and subthalamic nuclei in severe Parkinson's disease. , 2007, Brain : a journal of neurology.

[20]  Y. Fujii,et al.  EFFECTS OF ANTI‐PARKINSONIAN DRUGS ON NEUROBEHAVIOURAL CHANGES INDUCED BY BILATERAL 6‐HYDROXYDOPAMINE LESIONS IN RATS , 1999, Clinical and experimental pharmacology & physiology.

[21]  G. S. Russo,et al.  Subthalamic Nucleus Stimulation Modulates Thalamic Neuronal Activity , 2008, The Journal of Neuroscience.

[22]  R. Miall,et al.  Pedunculopontine nucleus stimulation improves akinesia in a Parkinsonian monkey , 2004, Neuroreport.

[23]  A. Benabid,et al.  Deep brain stimulation of the subthalamic nucleus for the treatment of Parkinson's disease , 2009, The Lancet Neurology.

[24]  Y Mayanagi,et al.  Results of stimulation and destruction of the posterior hypothalamus in man. , 1970, Journal of neurosurgery.

[25]  Stefan Kasicki,et al.  Theta-like rhythm in depth EEG activity of hypothalamic areas during spontaneous or electrically induced locomotion in the rat , 1995, Brain Research.

[26]  J. Vitek,et al.  Stimulation of the Subthalamic Nucleus Changes the Firing Pattern of Pallidal Neurons , 2003, The Journal of Neuroscience.

[27]  Zelma H T Kiss,et al.  Cellular mechanisms preventing sustained activation of cortex during subcortical high-frequency stimulation. , 2006, Journal of neurophysiology.

[28]  B. H. Bland.  Information Processing by Neuronal Populations: Anatomical, physiological, and pharmacological properties underlying hippocampal sensorimotor integration , 2008 .

[29]  Erwin B. Montgomery,et al.  Mechanisms of action of deep brain stimulation (DBS) , 2008, Neuroscience & Biobehavioral Reviews.

[30]  S. Gill,et al.  Bilateral deep brain stimulation of the pedunculopontine nucleus for Parkinson's disease , 2005, Neuroreport.

[31]  R. Vertes,et al.  Ascending projections of the posterior nucleus of the hypothalamus: PHA‐L analysis in the rat , 1995, The Journal of comparative neurology.

[32]  The pedunculopontine nucleus in Parkinson's disease: primate studies , 2008, British journal of neurosurgery.