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Objectives: This limited review examines the role of the reticular activating system (RAS), especially the pedunculopontine nucleus (PPN), one site of origin of bottom-up gamma, in the symptoms of bipolar disorder (BD). Methods: The expression of neuronal calcium sensor protein 1 (NCS-1) in the brains of BD patients is increased. It has recently been found that all PPN neurons manifest intrinsic membrane beta/gamma frequency oscillations mediated by high threshold calcium channels, suggesting that it is one source of bottom-up gamma. This review specifically addresses the involvement of these channels in the manifestation of BD. Results: Excess NCS-1 was found to dampen gamma band oscillations in PPN neurons. Lithium, a first line treatment for BD, was found to decrease the effects of NCS-1 on gamma band oscillations in PPN neurons. Moreover, gamma band oscillations appear to epigenetically modulate gene transcription in PPN neurons, providing a new direction for research in BD. Conclusions: This is an area needing much additional research, especially since the dysregulation of calcium channels may help explain many of the disorders of arousal in, elicit unwanted neuroepigenetic modulation in, and point to novel therapeutic avenues for, BD. © 2018 The Authors. Bipolar Disorders Published by John Wiley & Sons Ltd.


Documento: Artículo
Título:Bottom-up gamma and bipolar disorder, clinical and neuroepigenetic implications
Autor:Garcia-Rill, E.; D'Onofrio, S.; Mahaffey, S.C.; Bisagno, V.; Urbano, F.J.
Filiación:Center for Translational Neuroscience, University of Arkansas for Medical Sciences, Little Rock, AR, United States
IFIBYNE, CONICET, Universidad de Buenos Aires, Buenos Aires, Argentina
Palabras clave:Arousal; binding; Ca 2+ channels; gamma oscillations; lithium; NCS-1; neuroepigenetics; preconscious awareness; REM sleep; waking
Página de inicio:108
Página de fin:116
Título revista:Bipolar Disorders
Título revista abreviado:Bipolar Disord.


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---------- APA ----------
Garcia-Rill, E., D'Onofrio, S., Mahaffey, S.C., Bisagno, V. & Urbano, F.J. (2019) . Bottom-up gamma and bipolar disorder, clinical and neuroepigenetic implications. Bipolar Disorders, 21(2), 108-116.
---------- CHICAGO ----------
Garcia-Rill, E., D'Onofrio, S., Mahaffey, S.C., Bisagno, V., Urbano, F.J. "Bottom-up gamma and bipolar disorder, clinical and neuroepigenetic implications" . Bipolar Disorders 21, no. 2 (2019) : 108-116.
---------- MLA ----------
Garcia-Rill, E., D'Onofrio, S., Mahaffey, S.C., Bisagno, V., Urbano, F.J. "Bottom-up gamma and bipolar disorder, clinical and neuroepigenetic implications" . Bipolar Disorders, vol. 21, no. 2, 2019, pp. 108-116.
---------- VANCOUVER ----------
Garcia-Rill, E., D'Onofrio, S., Mahaffey, S.C., Bisagno, V., Urbano, F.J. Bottom-up gamma and bipolar disorder, clinical and neuroepigenetic implications. Bipolar Disord. 2019;21(2):108-116.