Neurotransmitters are chemicals synthesized inside the brain cells (neuron). Signals from the neuron travel out a thread-like extension called the axon, which connects to the next brain cell through a gap (synapse). There are the target neurons waiting for the signal.
There are many neurotransmitters in the brain. Serotonin, dopamine, acetylcholine are three of them.
Serotonin's role in the body has been associated mainly with mood, but it has major roles in temperature regulation, pain perception, sleep regulation, gut function (irritable bowel syndrome), major vessel constriction and relaxation, blood pressure control, and even neurodegenerative disorders like ALS have been associated with serotonin.
Dopamine is a neurotransmitter involved in motor function, behaviour, and cognition.
Acetylcholine functions both in the brain and peripheral neurons as a neuromodulator, it regulates gut function, sensory and autonomic nervous system, and sleep.
My major research is to define some of these neurotransmitters' involvement in disease.
Improvement of Self-Injury With Dopamine and Serotonin Replacement Therapy in a Patient With a Hemizygous PAK3 Mutation: A New Therapeutic Strategy for Neuropsychiatric Features of an Intellectual Disability Syndrome
Journal of Child Neurology
Gabriella A. Horvath and Maja Tarailo-Graovac and Tanja Bartel and Simone Race and Margot I. Van Allen and Ingrid Blydt-Hansen and Colin J. Ross and Wyeth W. Wasserman and Mary B. Connolly and Clara D. M. van Karnebeek
Improved strength on 5-hydroxytryptophan and carbidopa in spinal cord atrophy
Journal of the Neurological Sciences
Gabriella A. Horvath and Lorelyn Meisner and Kathryn Selby and Robert Stowe and Bruce Carleton
Debunking Occam's razor: Diagnosing multiple genetic diseases in families by whole exome sequencing.
Balci TB and Hartley T and Xi Y and Dyment DA and Beaulieu CL and Bernier FP and Dupuis L and Horvath G and Mendoza-Londono R and Prasad C and Richer J and Yang XR and Armour CM and Bareke E and Fernandez BA and McMillan HJ and Lamont R and Majewski J and Parboosingh J and Narayan Prasad A
The International Working Group on Neurotransmitter related Disorders (iNTD): A worldwide research project focused on primary and secondary neurotransmitter disorders.
Opladen T and Cortès-Saladelafont E and Mastrangelo M and Horvath G and Pons R and Lopez-Laso E and Fernández-Ramos JA and Honzik T and Pearson T and Friedman J and Scholl-Bürgi S and Wassenberg T and Jung-Klawitter S and Kuseyri O and Jeltsch K and Kurian MA and Garcia-Cazorla À and International Working Group on Neurotransmitter related disorders (iNTD)
Eye Findings on Vigabatrin and Taurine Treatment in Two Patients with Succinic Semialdehyde Dehydrogenase Deficiency.
Horvath GA and Hukin J and Stockler-Ipsiroglu SG and Aroichane M
Secondary neurotransmitter deficiencies in epilepsy caused by voltage-gated sodium channelopathies: A potential treatment target?
Horvath GA and Demos M and Shyr C and Matthews A and Zhang L and Race S and Stockler-Ipsiroglu S and Van Allen MI and Mancarci O and Toker L and Pavlidis P and Ross CJ and Wasserman WW and Trump N and Heales S and Pope S and Cross JH and van Karnebeek CD
Deep brain stimulation and dantrolene for secondary dystonia in x-linked adrenoleukodystrophy.
van Karnebeek C and Horvath G and Murphy T and Purtzki J and Bowden K and Sirrs S and Honey CR and Stockler S
Mitochondrial carbonic anhydrase VA deficiency resulting from CA5A alterations presents with hyperammonemia in early childhood.
van Karnebeek CD and Sly WS and Ross CJ and Salvarinova R and Yaplito-Lee J and Santra S and Shyr C and Horvath GA and Eydoux P and Lehman AM and Bernard V and Newlove T and Ukpeh H and Chakrapani A and Preece MA and Ball S and Pitt J and Vallance HD and Coulter-Mackie M and Nguyen H
A novel recurrent mutation in ATP1A3 causes CAPOS syndrome.
Demos MK and van Karnebeek CD and Ross CJ and Adam S and Shen Y and Zhan SH and Shyr C and Horvath G and Suri M and Fryer A and Jones SJ and Friedman JM and FORGE Canada Consortium
Long-term outcomes of blood phenylalanine concentrations in children with classical phenylketonuria.
Hartnett C and Salvarinova-Zivkovic R and Yap-Todos E and Cheng B and Giezen A and Horvath G and Lillquist Y and Vallance H and Stockler-Ipsiroglu S
Three years experience with dried blood spot a-glucosidase screening for Pompe disease in British Columbia, Canada.
Horvath G and Sirrs S and Stockler S and Salvarinova-Zivkovic R and Vallance H and Waters P
Profound neonatal hypoglycemia and lactic acidosis caused by pyridoxine-dependent epilepsy.
Mercimek-Mahmutoglu S and Horvath GA and Coulter-Mackie M and Nelson T and Waters PJ and Sargent M and Struys E and Jakobs C and Stockler-Ipsiroglu S and Connolly MB
The use of parenteral nutrition for the management of PKU patient undergoing chemotherapy for lymphoma: a case report.
Salvarinova-Zivkovic R and Hartnett C and Sinclair G and Dix D and Horvath G and Lillquist Y and Stockler-Ipsiroglu S
Failure of repeated cyclophosphamide pulse therapy in childhood cerebral X-linked adrenoleukodystrophy.
Horvath GA and Eichler F and Poskitt K and Stockler-Ipsiroglu S
Hemiplegic migraine, seizures, progressive spastic paraparesis, mood disorder, and coma in siblings with low systemic serotonin.
Horvath GA and Selby K and Poskitt K and Hyland K and Waters PJ and Coulter-Mackie M and Stockler-Ipsiroglu SG
Treatment of intractable epilepsy in a female with SLC6A8 deficiency.
Mercimek-Mahmutoglu S and Connolly MB and Poskitt KJ and Horvath GA and Lowry N and Salomons GS and Casey B and Sinclair G and Davis C and Jakobs C and Stockler-Ipsiroglu S
Autosomal recessive GTP cyclohydrolase I deficiency without hyperphenylalaninemia: evidence of a phenotypic continuum between dominant and recessive forms.
Horvath GA and Stockler-Ipsiroglu SG and Salvarinova-Zivkovic R and Lillquist YP and Connolly M and Hyland K and Blau N and Rupar T and Waters PJ
Newborn screening for MCAD deficiency: experience of the first three years in British Columbia, Canada.
Horvath GA and Davidson AG and Stockler-Ipsiroglu SG and Lillquist YP and Waters PJ and Olpin S and Andresen BS and Palaty J and Nelson J and Vallance H
Report of a fourth individual with a lethal syndrome of choanal atresia, athelia, evidence of renal tubulopathy, and family history of neck cysts.
Horvath GA and Armstrong L
Neurotransmitter and parasympathetic response in patients with dysautonomia, in collaboration with Dr. Jean-Paul Collet (CFRI). I follow several patients with dysautonomia in clinic, who had their baseline catecholamine measurements and then enroll them in this study to evaluate the effect of Chines massage therapy and Tai-Chi on their parasymapthetic nervous system.
Neurotransmitter changes in patients with presyncope, in collaboration with Dr. Shubayan Sanatani (BCCH) and Dr. Victoria Claydon (SFU) I evaluate pateints in clinic with complex autonomic dysfunction and presyncope, and then enroll them in this study where they have sophisticated investigations with a tilt table test at the SFU Kinesiology Lab. I work on the plasma catecholamine and serotonin level interpretations in relation to the other test findings.
Characterization of a new genetic disorder associated with hemiplagic migraines, coma, progressive spasticity, weakness, seizure disorder, spinal cord atrophy, and systemic serotonin deficiency. The research of a family with the above described phenotype lead to discovery of a new gene that involves cytoskeletal and axonal transport, and will cause cytoskeletal aggregates in neurons, that will keep neurotransmitter transporters (serotonin transporter) and other membrane expressed proteins (e.g. Na/K ATPase). This disorder has similarities with ALS, and could be a major breakthrough in ALS research. this research is done partly in collaboration with Dr. Randy Blakely at the Vanderbilt University in Nashville, who has done the exome sequencing in the family. I spent 6 weeks in his lab to do the molecular and biochemical studies. Before traveling there I developed a radioactive isotope method for measuring the serotonin trasnporter activity in vitro in these patients.Grants
Rare Diseases Foundation: Molecular Genetic Analysis of the MMSD Gene in a Patient with Recurrent Metabolic Coma and Abnormal Urinary Excretion of 3-Hydroxyisobutyric Acid, 2009
Rare Diseases Foundation: Evaluation of choline and acetylcholine pathways in a child with progressive cholinergic failure, 2010
Rare Diseases Foundation:in vivo Phosphorus Magnetic Resonance Spectroscopy of the Muscle in Two Siblings with Unexplained Muscle Weakness, 2009Honours & Awards
Clinical Investigator Program, two year scholarship awarded (July 2008 to June 2010)
Laura MacRae Award 2007 (awarded to outstanding graduate student in the Dept. of Pediatrics, UBC, by the College of Physicians and Surgeons of British Columbia, June 2007
Rookie of the Year 2007, (awarded by the Pediatric Residents, UBC, at the Annual Graduation and Awards Dinner), June 2007.Research Group Members
Nicola Fameli, Research associate, Staff scientist