LSU Health Shreveport
Department of Pharmacology, Toxicology & Neuroscience
1501 Kings Hwy
Shreveport, LA 71103
Kevin S. Murnane, PhD
Associate Professor of Pharmacology, Toxicology and Neuroscience; Associate Professor of Psychiatry; Director of Basic Science Research for Louisiana Addiction Research Center
Bachelor of Science, Biology and Psychology - University of Georgia
PhD, Neuroscience - Emory University
Latest News from the Murnane Lab
Invited Seminar and Symposia Presentations:
- Murnane KS, Phillips-Lindsey L, Daphney CM, Oppong-Damoah A, Uchakin PN, Abney SE, Uchakina ON, Khusial RD, and Akil A (2019) The cannabinoid receptor 2 agonist, β-caryophyllene, improves memory function in aged mice and reduces key cytokines associated with aging. Annual Meeting of the International Society for Cannabinoid Research
- Murnane KS (2019) Neuroinflammation as a target for the development of novel disease modifying therapeutics for central nervous system disorders. Mercer College of Pharmacy Research Seminar Series
- Murnane KS, Guner OF, Bowen JP, Moniri NH, Rambacher KM, Murphy TJ, Daphney CM, Oppong-Damoah A, and Rice KC (2019) Developing serotonin 2A receptor activators with reduced psychoactivity as new treatments for substance dependence. Annual Meeting of the American Society for Pharmacology and Experimental Therapeutics
- Murnane KS, Daphney CM, and Canal CE (2019) Differences in serotonin 2A receptor expression and function across age, sex, and genotype. Annual Meeting of the Behavioral Pharmacology Society (Satellite meeting of the Annual Meeting of the American Society for Pharmacology and Experimental Therapeutics)
- Chitre NM, Wood B, Ray A, Moniri NH, and Murnane KS (2019) Assessing the neuroprotective effects of docosahexaenoic acid in an advanced-stage Parkinson’s disease model in rats. Atlanta Research Conference
- Oppong-Damoah A, Wood BJ, Blough BE, and Murnane KS (2019) Caryophyllene oxide is more potent than beta caryophyllene in attenuating the abuse related effects of ethanol. Eleventh Annual Meeting of the Biology, Behavior, and Chemistry Conference
- Robinson H and Murnane KS (2019) MUBS 2018 experience. Mercer University "Bear Day" Research Symposium
- Kelley K and Murnane KS (2019) Development of a transdermal patch formulation of novel ADHD medications. Mercer University "Bear Day" Research Symposium
- Murnane KS (2019) DD Therapeutics. Panel discussion at Health Connect South
Our research group is focused on the etiology, pathophysiology, pharmacology, neurobiology, and treatment of disorders of the central nervous system (CNS). Areas of special emphasis include substance use disorders, comorbid mood changes and cognitive impairments, as well as neurodegenerative decline following exposure to abused substances. Recent studies have focused on the relationships between natural products, neuroinflammation, oxidative stress, and brain monoamine systems that are associated with mood, motivation, and cognition. We have also recently begun to study the intersections between brain and cardiovascular disease. Our long-term ambition is that the knowledge gained in these studies will allow for the development of new therapeutics with first-in-class disease modifying effects.
Students in our laboratory gain competencies in cutting-edge research techniques such as peripheral surgical and neurosurgical techniques, analytical chemistry methods, microdialysis, neuroimaging, in vivo pharmacology, cognitive testing, operant conditioning, immunohistochemistry, western blotting, optogenetics, electroencephalography, molecular biology, blood-brain barrier transport, and cell culture.
- Central Theme: Neuroinflammation and Drug Discovery and Development
- Alcohol Use Disorder
- Stimulant Use Disorder
- Alzheimer's Disease
- Brain Targeted Drug Delivery
- Parkinson's Disease (PD)
- Additional Research
Our lab focuses on studying neuroinflammation and understanding the mechanisms involved in inflammatory responses within the brain. We study the role of neuroinflammation in the context of different disease states, insults, and stressors. Understanding the context, course and duration of the neuroinflammatory response is vital to understanding the corresponding behavioral and biochemical consequences. Additionally, neuroinflammation plays a central role in the underlying pathophysiology of neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease as well as various substance use disorders such as alcohol use disorder and stimulant use disorder. Thus, the aim of our laboratory is to understand the role of neuroinflammation in the pathophysiology of several classes of disorders listed below and study the role of novel, anti-inflammatory compounds as potential therapeutic interventions for these conditions.
The image on the left depicts Glial fibrillary acidic protein (GFAP) staining for astrocytes as a marker of astrogliosis in the rat hippocampus.
Approximately 20 million adults in the United States suffer from alcohol use disorder (AUD)
Current treatments for AUD include naltrexone, disulfuram, and acomprosate. However, a high percentage of AUD patients remain refractory to such therapy. Thus, we are studying neuropharmacological and neurobiological systems that mediate alcohol abuse and dependence, with an emphasis on brain serotonin systems and neuroinflammation to potentially develop new therapeutics for AUD. We specifically use techniques and measures such as the two bottle-choice ethanol drinking paradigm, ethanol-induced conditioned place preference (CPP) and ethanol-induced loss of righting reflex (LORR) assay. We use these assays to evaluate the potency and efficacy of several anti-inflammatory compounds such as the phytochemical beta-caryophyllene (BCP), its derivative oxide (BCPO) and the synthetic psychedelic 2,5-dimethoxy-4-iodoamphetamine (DOI) for AUD.
The graph on the left depicts data from mice drinking either ethanol or water using the two bottle-choice ethanol drinking paradigm
Our lab is involved in assessing the persistent behavioral and neurochemical effects of exposure to various classes of stimulants such as methamphetamine, MDMA and synthetic cathinones such α-pyrrolidinopropiophenone (α-PPP). Additionally, we also aim to identify novel drug targets to prevent the devastating adverse events associated with stimulant overdose. Thus, current research in our laboratory involves characterizing the neurotoxic effects of stimulant overdose such as stimulant-induced lethality, hyperthermia, convulsions, seizures and monoamine neurochemistry depletion. Additionally, we also study various agents like HT2A receptor antagonist M100907 ,the sigma 1 (σ1) receptor antagonist BD 1047 and other anti-inflammatory compounds and peptides to attenuate adverse effects of stimulant overdose using techniques such as behavioral pharmacology,surgical telemetric probe implantation, electroencephalography and neurochemistry analysis by High Performance Liquid Chromatography (HPLC).
TThe image on the left depicts representative electroencephalography waveforms over a period of 60 s following administration of 78 mg/kg of methamphetamine (or baseline). Data showing the effects of pretreatment with vehicle, M100907 (1 mg/kg), BD 1047 (10 mg/kg), and the combination of M100907/BD 1047 (1/10 mg/kg) on seizures are shown.
Alzheimer's disease (AD) is responsible for major financial and health-care burdens to society. It is estimated that the costs are likely to grow as our population ages further. Current therapeutics for AD only provide transient symptom management and do not alter the course of the disease. Interestingly, AD affects a greater proportion of females as compared to males. A leading hypothesis for the pathology of AD involves the production of toxic forms of Amyloid-beta plaques and neurofibrillary tangles in the brain which trigger inflammation-mediated neurotoxicity. The cholinergic system is most widely studied for AD related pathophysiology. However, more recent studies also implicate other neurotransmitter systems such as serotonin and norepinephrine which play vital roles in modulating behaviors such as fear and anxiety. Thus, our research focuses on studying different neurotransmitter systems implicated in AD and characterizing sex differences and epigenetic alterations in AD. Additionally we are also investigating the role of novel anti-inflammatory agents as potential therapeutics for AD using techniques such as behavioral pharmacology, autoradiography, proteomics, immunohistochemistry and neurochemical analysis.
The image on the left shows App knock-in mice from our breeding colony that were specifically engineered by researchers at the Riken Brain Science Institute in Japan to display AD-like pathology.
The blood-brain barrier (BBB) limits the therapeutic use of large molecules and peptides as it prevents them from passively entering the brain following administration by conventional routes. We use nanotechnology drug delivery systems for encapsulating peptides such as Oxytocin and Neuropeptide Y to increase their brain bioavailability through active transport and increase their duration of action through encapsulation and sustained release. Preclinical and clinical studies suggest pro-social behavioral effects of these peptides and therapeutic promise. Thus, we specifically evaluate the therapeutic effects and increased bioavailability of these formulations for conditions such as alcohol use disorder (AUD) , Substance use disorder and opioid use disorder using in vitro techniques such as cell-culture model of the BBB, and in vivo techniques such as bioimaging, cerebrospinal fluid analysis, behavioral testing and EEG (electroencephalography).
The image on the left shows brain uptake in mice at 30 minutes (above) or 4 hours (below) of an encapsulated large-molecule dye in a nanoformulation (left and middle). The red uptake in the Tf-NP nanoparticles shows that our technology has actively transported this dye into the brain successfully.
Parkinson’s Disease (PD) is amongst the most common neurodegenerative diseases. It is clinically manifested by motor symptoms including resting tremors, postural instability, rigidity, and bradykinesia. The neuropathogenesis of PD symptomology is directly linked to the selective loss of dopaminergic neurons in the substantia nigra pars compacta (SN), where cell death leads to subsequent depletion of the key neurotransmitter dopamine (DA). Polyunsaturated fatty acids (PUFA), including the family of omega-3 fatty acids (w3FA) that contains a-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) have a long record of linkage to brain function. Thus, our research focuses on studying the neuroprotective and dopamine synthesizing effects of omega-3 fatty acids for PD and investigating the potential mechanisms through which they act using behavioral, molecular and neurochemical techniques.
The image above shows a UHPLC coupled to electrochemical detectors (ECD) used to quantify tissue levels of neurotansmitters such as Dopamine and its primary metabolite DOPAC.
Additional research focus areas of the laboratory include:
- Studying the effects of a high fat diet on monoamine neurochemistry
- Comparing the psychoactive effects of various psychedelics such as 2,5-Dimethoxy-4-iodoamphetamine (DOI) and other tryptamines
- Investigating the anxiolytic and sedative properties of various naturally occurring sesquiterpenes
- Using optogenetics as a tool to investigate into mechanisms associated with anxiety with the ultimate aim to develop therapeutic interventions for anxiety related disorders
The synthetic cathinone 3, 4-methylenedioxypyrovalerone increases impulsive action in rats. WS Hyatt, CE Hirsh, LN Russell, NM Chitre, KS Murnane, KC Rice, ... Behavioural Pharmacology 31 (4), 309-321, 2020
Docosahexaenoic acid protects motor function and increases dopamine synthesis in a rat model of Parkinson's disease via mechanisms associated with increased protein kinase … NM Chitre, BJ Wood, A Ray, NH Moniri, KS Murnane, Neuropharmacology 167, 107976, 1 2020
Immune Modulatory Effects of Caryophyllene Oxide in Alcohol Related Behaviors. A Oppong-Damoah, SE Abney, BM Gannon, BE Blough, PN Uchakin, ..., The FASEB Journal 34 (S1), 1-1, 2020
Transdermal Delivery of the Free Base of 3-Fluoroamphetamine: In Vitro Skin Permeation and Irritation Potential. Y Jiang, KS Murnane, BE Blough, AK Banga, AAPS PharmSciTech 21 (3), 1-8, 1 2020
The acute toxic and neurotoxic effects of 3, 4-methylenedioxymethamphetamine are more pronounced in adolescent than adult mice. NM Chitre, MS Bagwell, KS Murnane, Behavioural Brain Research 380, 112413, 1 2020
The pharmacokinetics of 3-fluoroamphetamine following delivery using clinically relevant routes of administration. Y Jiang, A Ray, MSA Junaid, SA Bhattaccharjee, K Kelley, AK Banga, ..., Drug Delivery and Translational Research 10 (1), 271-281, 2 2020
Nanoformulations of neuropeptides and method of making same. MJ D'souza, K Murnane, US Patent App. 16/510,466, 2020
Omega-3 Fatty Acids as Druggable Therapeutics for Neurodegenerative Disorders. NM Chitre, NH Moniri, KS Murnane, CNS & Neurological Disorders-Drug Targets (Formerly Current Drug Targets-CNS …, 1 2019
Effects of the synthetic psychedelic 2, 5-dimethoxy-4-iodoamphetamine (DOI) on ethanol consumption and place conditioning in male mice. A Oppong-Damoah, KE Curry, BE Blough, KC Rice, KS Murnane, Psychopharmacology 236 (12), 3567-3578, 3 2019
A Classroom Activity to Increase Student Pharmacists Confidence in Dealing with the Opioid Epidemic. KS Murnane, JM Augustine, M Quesnel, L Marshall, JG Strom, American Journal of Pharmaceutical Education 83 (9), 2019
The cannabinoid receptor 2 agonist, β-caryophyllene, improves working memory and reduces circulating levels of specific proinflammatory cytokines in aged male mice. LP Lindsey, CM Daphney, A Oppong-Damoah, PN Uchakin, SE Abney, ..., Behavioural brain research 372, 112012, 6 2019
Transdermal Delivery of Phenethylamine Monoamine Releasers. KS Murnane, AK Banga, SS Ganti, Y Jiang, A Puri, US Patent App. 16/346,180, 2019
Repeated administration of synthetic cathinone 3, 4-methylenedioxypyrovalerone persistently increases impulsive choice in rats. WS Hyatt, MD Berquist, NM Chitre, LN Russell, KC Rice, KS Murnane, ..., Behavioural pharmacology 30 (7), 555-565, 2 2019
M100907 and BD 1047 attenuate the acute toxic effects of methamphetamine. A Ray, CE Canal, JC Ehlen, KC Rice, KS Murnane, Neurotoxicology 74, 91-99, 2 2019
Skin delivery and irritation potential of phenmetrazine as a candidate transdermal formulation for repurposed indications. Y Jiang, KS Murnane, SA Bhattaccharjee, BE Blough, AK Banga, The AAPS journal 21 (4), 70, 5 2019
The synthetic cathinone psychostimulant α‐PPP antagonizes serotonin 5‐HT2A receptors: In vitro and in vivo evidence. Y Chen, BE Blough, KS Murnane, CE Canal, Drug testing and analysis 11 (7), 990-998, 1 2019
The sesquiterpene beta-caryophyllene oxide attenuates ethanol drinking and place conditioning in mice. A Oppong-Damoah, BE Blough, A Makriyannis, KS Murnane, Heliyon 5 (6), e01915, 4 2019
The adrenergic receptor antagonist carvedilol interacts with serotonin 2A receptors both in vitro and in vivo. KS Murnane, OF Guner, JP Bowen, KM Rambacher, NH Moniri, ..., Pharmacology Biochemistry and Behavior 181, 37-45, 5 2019
The Synthetic Cathinone α-PPP Acts as a Competitive Antagonist at Human 5-HT2A Receptors. Y Chen, B Blough, K Murnane, C Canal, The FASEB Journal 33 (1_supplement), 664.17-664.17, 2019
Caryophyllene Oxide is More Potent than Beta Caryophyllene in Attenuating the Abuse-Related Effects of Ethanol. A Oppong-Damoah, BJ Wood, B Blough, KS Murnane, The FASEB Journal 33 (1_supplement), 499.6-499.6, 2019
While we are not currently recruiting Post-doctoral Fellows, quality candidates will always be considered. To enquire about opportunities, contact Dr. Murnane.
Graduate students interested in conducting research in the Murnane lab should review the current laboratory research directions and contact Dr. Murnane.
Undergraduate Research Assistants
We are not currently hiring any additional undergraduates. However, positions can become available during the summer.
Medical Students, Residents, and Fellows
The Murnane laboratory has a number of research projects available for any Medical Students, Residents, and Fellows.