CONTACT INFORMATIONDepartment of Psychiatry
University of Illinois at Chicago
1601 W. Taylor Street Room 409 ,
Chicago, IL 60612
Office Phone: 312-355-1464
Assistant: Marianela Nelson
Agis-Balboa RC, Guidotti A, and Pinna G: Allopregnanolone biosynthesis is downregulated in the prefrontal cortex/Brodmann’s area 9 (BA9) of depressed patients. Psychopharmacology. Submitted.
Pinna G: Targeting neurosteroidogenesis as therapy for PTSD. Frontiers in Pharmacology. Submitted.
Pinna G and Rasmusson AM: Upregulation of neurosteroid biosynthesis as a pharmacological strategy to improve behavioral deficits in a putative mouse model of PTSD. J. Neuroendocrinology. 24:102-16. 2012
Schüler Nin M, Martinez LA, Pibiri F, Nelson M and Pinna G: Neurosteroids reduce social isolation-induced behavioral deficits: a proposed link with neurosteroid-mediated upregulation of BDNF expression. Front. Endocrin. 2:73. doi: 10.3389/fendo.2011.00073. 2011
Nelson M and Pinna G: S-norfluoxetine infused into the basolateral amygdala increases allopregnanolone levels and reduces aggression in socially isolated mice. Neuropharmacology. 60:1154-1159. 2011
Pinna G: In a mouse model relevant for PTSD, selective brain steroidogenic stimulants (SBSSs) improve behavioral deficits by normalizing allopregnanolone biosynthesis. Behavioural Pharmacology. 21:438-450. 2010.
Pinna G, Costa E, and Guidotti A: SSRIs act as selective brain steroidogenic stimulants (SBSSs) at low doses that are inactive on 5-HT reuptake. Current Opinions in Pharmacology 9:24-30. 2009.
Pinna G, Agis-Balboa R, Pibiri F, Nelson M, Guidotti A, and Costa E: Neurosteroid biosynthesis regulates sexually dimorphic fear and aggressive behavior in mice. Neurochemical Research. 33:1990-2007. 2008.
Pibiri F, Nelson M, Costa E, Guidotti A, and Pinna G: Decreased corticolimbic allopregnanolone expression during social isolation enhances contextual fear: A model relevant for posttraumatic stress disorder. Proc. Natl. Acad. Sci. USA 105:5567-5572. 2008. (media release: Click here.)
Agís-Balboa RC, Pinna G, Pibiri F, Kadriu B, Costa E, and Guidotti A: Downregulation of 5a-reductase type I mRNA expression in cortico-limbic glutamatergic neurons in socially-isolated mice. Proc. Natl. Acad. Sci. USA. 104:18736-18741. 2007. (media release: Click here)
Pinna G, Agis Balboa RC, Zhubi A, Matsumoto K, Grayson DR, Costa E and Guidotti A: Imidazenil and diazepam increase locomotor activity in mice exposed to protracted social isolation. Proc. Natl. Acad. Sci. USA 103:4275-4280. 2006.
Pinna G, Costa E, and Guidotti: Fluoxetine and norfluoxetine stereospecifically and selectively increase brain neurosteroid content at doses inactive on 5-HT reuptake. Psychopharmacology. 186:362-372. 2006.
Agis-Balboa RC, Pinna G, Zhubi A, Veldic M, Costa E and Guidotti A: Location and expression of brain enzymes catalyzing neurosteroid biosynthesis. Proc. Natl. Acad. Sci. USA 103:14602-14607. 2006.
Rasmusson AM, Pinna G, Weisman D, Paliwal P, Gottschalk C, Charney D, Krystal J and Guidotti A: Decreased cerebrospinal fluid allopregnanolone levels in women with PTSD. Biol. Psychiatry. 60: 704-713. 2006.
Pinna G, Costa E, and Guidotti A: Changes in brain testosterone and allopregnanolone elicit aggressive behavior. Proc. Natl. Acad. Sci. USA 102:2135-2140. 2005.
Pinna G, Costa E and Guidotti A: Fluoxetine and norfluoxetine stereospecifically facilitate pentobarbital sedation by increasing neurosteroids. Proc. Natl. Acad. Sci. USA 101:6222-6225. 2004.
Pinna G, Dong E, Matsumoto K, Costa E and Guidotti A: In socially isolated mice, the reversal of brain allopregnanolone down-regulation mediates the anti-aggressive action of fluoxetine. Proc. Natl. Acad. Sci. USA 100:2035-2040. 2003
GRAZIANO PINNA, PhD
1. Mechanism of action of antidepressant, anxiolytic, and antiaggressive drugs in several mouse models of affective/cognitive disorders, including aggressive behavior, schizophrenia, and PTSD
2. Developing new therapies for PTSD and anxiety disorders
3. Epigenetic mechanisms and psychiatric disorders, including schizophrenia
4. Understanding emotional brain circuits that mediate cognitive and affective processes in PTSD mouse models
5. Physiological role of neurosteroid allopregnanolone on GABAA receptor function
6. Pharmacology of GABAA receptor modulators
7. Mechanisms that lead to anabolic androgenic steroid (AAS)-induced behavioral deficits and the study of molecules that reverse the behavioral and neurochemical dysfunction induced by AAS treatment
8. Function of GABAA receptors in mouse models of anxiolytic drug tolerance and dependence
American Medical Association; American Psychiatric Association; Illinois Psychiatric Society; Chicago Medical Society; American Board of Psychiatry and Neurology;Society for Neuroscience (1995);Society for Women’s Health Research (2001)
Title:“Expression, behavioral effects and fertility parameters of β-defensins and neuropeptide Y in a mouse model of post-traumatic stress disorder (PTSD) related to neurosteroidi biosynthesis downregulation”. Supported by FAPESP. Brief description of project’s goals: The goal of this study is to investigate the neurosteroid-mediated regulation of two anti-microbial peptide, (NPY and -defensin), in a mouse model of PTSD. The role of NPY and -defensin on emotions and fertility parameters will be related to levels of neurosteroids (allopregnanolone, 5alpha DHP, and progesterone; testosterone; 5alphaDHT, etc) in male and female rodents.
Title: “Neurosteroid levels in patients with PTSD”. Supported by VA.Brief description of project’s goals: The goal of this study is to investigate the serum and CSF levels of neurosteroids (allopregnanolone, 5alpha DHP, and progesterone; testosterone; 5alphaDHT; DHEA; DHEAS) in male and female (across the menstrual cycle) PTSD patients.
Title: “Effects of Ganaxolone on a mouse model of PTSD”. Supported by Marinus Pharmaceuticals Inc. Supported by Marinus Pharmaceuticals Inc.Brief description of project’s goals: The aim of this investigation is to study the behavioral effects of ganaxolone, an allopregnanolone analog that directly activates GABAA receptors in a mouse model of PTSD. Ganaxolone may offer a safe therapeutic alternative in patients who cannot adequately synthesize allopregnanolone and in whom administration of a steroidogenic agent is ineffective because neurosteroidogenesis is greatly impaired. A multisite Phase II trial of the efficacy and safety of ganaxolone in PTSD is currently under process.
Peer Reviewed Publications:
1. Pinna G: The Neurosteroidogenic Action of Fluoxetine Unveils the Mechanism for the Anxiolytic Property of SSRIs; Chap. 2 Fluoxetine: Pharmacology, Mechanisms of Action and Potential Side Effects, Pharmacology - Research, Safety Testing and Regulation series Pinna G. (Editor) Nova Biomedical Publ. 2015.
2. Pinna G, Rasmusson A. Ganaxolone improves behavioral deficits in a mouse model of post-traumatic stress disorder”. Front. Cell. Neurosci. 8:256.2014 doi: 10.3389/fncel.2014.00256 (Media release).
3. Agis-Balboa RC, Guidotti A, Pinna G. Allopregnanolone biosynthesis is downregulated in the prefrontal cortex/Brodmann’s area 9 (BA9) of depressed patients. Psychopharmacology. 231(17):3569-80. 2014. PMID:24781515 (Media release).
4. Pinna G. Therapeutic strategies to increase neurosteroidogenesis and improve PTSD by enhancing GABAergic neurotransmission. Innovations in Pharmaceuticals and Pharmacotherapy 1 (4, Special Issue, Neuropharmacology), 285-296, 2014.
5. Pinna G. Targeting neurosteroidogenesis as therapy for PTSD. Front. Pharmacol. Dec. 2014 | doi: 10.3389/fphar.2014.00166
6. Pinna G and Rasmusson AM: Upregulation of neurosteroid biosynthesis as a pharmacological strategy to improve behavioral deficits in a putative mouse model of PTSD. J. Neuroendocrinology. 24:102-16. 2012
Editor of Books:
Fluoxetine:Pharmacology,Mechanisms of Action and Potential Side Effects.
Nova Publishers New York.(Editor:G.Pinna)