Doodipala Reddy, Ph.D.
Assistant Professor of Pharmacology   

Phone: (919) 513-6549
E-mail: samba_reddy@ncsu.edu

Research Area:

Epilepsy, Molecular Mechanisms of Neurosteroids, and Antiepileptic Drug Development

Current Research:

Dr. Reddy’s major research goals are to understand the molecular pathophysiology and develop novel therapeutic strategies for epilepsy, with an emphasis on catamenial epilepsy and temporal lobe epilepsy. Current work in the lab is focused on the role of steroid hormones and endogenous neurosteroids in epilepsy and related brain disorders. Neurosteroids are steroids synthesized locally within the brain that rapidly change neural excitability and seizure susceptibility by non-genomic mechanisms, principally via postsynaptic GABAA receptors, a subtype of the major inhibitory neurotransmitter GABA that play critical role in epileptogenesis and epilepsy.

Epilepsy, a neurological disorder involving repeated occurrence of uncontrolled seizures, affects some 50 million people worldwide and about 2.5 million individuals in the United States. Standard current treatment is to prescribe one of the more than 25 seizure-suppressing medications known as antiepileptic drugs. However, nearly 30% of people with epilepsy have intractable seizures that do not respond to even the best available treatment. Temporal lobe epilepsy is a chronic condition characterized by recurrent seizures arising from one or both temporal lobes of the brain, specially the hippocampus. Temporal lobe epilepsy is often drug resistant and novel approaches are being explored in Dr. Reddy lab to treat this devastating disorder that impacts nearly 40% of patients with epilepsy.

Women with epilepsy often report an increase in seizures at the time of menstruation, a condition referred to as "catamenial epilepsy”. Catamenial epilepsy is a form of epilepsy in which seizures are clustered around specific points in the menstrual cycle, most frequently during the perimenstrual or periovulatory phase.  Catamenial epilepsy affects 39-60% of women with epilepsy, and currently there is no specific drug to treat catamenial seizures. The goal of Dr. Reddy’s lab is to develop a drug therapy that, without undesirable side effects, will prevent or control catamenial seizures in women with epilepsy. His lab is testing the effectiveness of neuroactive steroid therapy based on a rational strategy in catamenial model in rats. Because progesterone plays a vital role in women with epilepsy, his lab is uncovering the molecular mechanism of progesterone actions in the brain using genetic, molecular and electrophysiological approaches. Progesterone regulation of the GABA-A receptor plasticity is being explored as a novel paradigm relevant to catamenial epilepsy.

More recent studies include understanding the role of androgenic neurosteroids in epilepsy and aging. Dr. Reddy has found that the testosterone-derived neurosteroid 3a-androstanediol has anticonvulsant properties and thus it could serve as an endogenous protective agent in the brain.

Equipment and Skills:

Dr. Reddy lab is utilizing multiple techniques in current research projects including pharmacological (animal epilepsy models), molecular biological (real-time PCR, Western blots and immunohistochemistry), electrophysiological (patch-clamp and extracellular recordings in hippocampus slices), and transgenic mouse approaches. Dr. Reddy group has active collaborations with several neuroscientists within and at outside of the Research Triangle area.

Representative Publications:

Reddy DS. Mass spectrometric assay and physiological-pharmacological activity of androgenic neurosteroids. Neurochem International 2008;52(4-5):541-553.

Reddy DS and Zeng YC. Differential anesthetic activity of ketamine and the GABAergic neurosteroid allopregnanolone in mice lacking progesterone receptor A and B subtypes. Methods Find Exp Clin Pharmacol 2007; 29(10): 659-664.

Reddy DS. Premenstrual catamenial epilepsy. Women’s Health 2007 3(2): 195-206.

Rao MV, Hattiangady B, Reddy DS and Shetty AK. Hippocampal neurodegeneration, spontaneous seizures and mossy fiber sprouting in F344 rat model of temporal lobe epilepsy. J Neurosci Res 2006, 83(6):1088-105.

Reddy DS. Physiological role of adrenal deoxycorticosterone-derived neuroactive steroids in stress-sensitive conditions. Neuroscience 2006; 138:911-920.

Reddy DS, Chien B, and Ramu K.  A high-performance liquid chromatography-tandem mass spectrometry assay of the androgenic neurosteroid 3a-androstanediol in plasma. Steroids 2005, 70:879-885.

Reddy DS. Role of neurosteroids in catamenial epilepsy. Epilepsy Res 2004, 62:99-118.

Reddy DS, Castenada DA, O’Malley BW, and Rogawski MA. Antiseizure activity of progesterone and neurosteroids in progesterone receptor knockout mice. J Pharmacol Exp Therap 2004, 310: 230-239.

Reddy DS. Testosterone modulation of seizure susceptibility is mediated by neurosteroids 17b-estradiol and 3a-androstanediol. Neuroscience 2004, 129:195-207.

Reddy DS and Woodward R. Ganaxolone: a prospective overview. Drugs Future 2004, 29:227-242.

Reddy DS. Anticonvulsant activity of the testosterone-derived neurosteroid 3a-androstanediol. NeuroReport 2004, 15: 515-518.

Reddy DS. Is there a physiological role for the neurosteroid THDOC in stress-sensitive conditions? Trends Pharmacol Sci 2003; 24: 103-106.

Reddy DS and Rogawski MA. Stress-induced deoxycorticosterone-derived neurosteroids modulates GABA-A receptor function and seizure susceptibility. J Neurosci 2002, 22: 3795-3805.

Reddy DS, Kim Y-H and Rogawski MA. Neurosteroid withdrawal model of perimenstrual catamenial epilepsy. Epilepsia 2001, 42: 328-336.

Reddy Lab Personnel:

Doodipala S. Reddy, Ph.D. Principal Investigator
Seema Briyal, Ph.D. Postdoctoral Fellow
Weifang Zhang, M.S. Research Technician
Omkaram Gangisetty, Ph.D. Postdoctoral Research Associate

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