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158 Journal of Veterinary Behavior, Vol 5, No 3, May/June 2010
Studzinski, C.M., Araujo, J.A., Milgram, N.W., 2005. The canine model of
human cognitive aging and dementia: Pharmacological validity of the
model for assessment of human cognitive-enhancing drugs Prog. Neu-
ro-Psychopharm. Biol. Psychiatry 29, 489–498.
TRANSLATIONAL APPROACHES IN NEUROPSYCHIATRICDRUG DISCOVERYJ.J. Hagan1,*1CEO, Global Medical Excellence Cluster (GMEC),King’s College, Hodgkin Building, Guy’s Campus,London, SE1 1UL, UK*Corresponding author: [email protected]
Schizophrenia and depression have remained resistant toattempts to understand their biological causes. As a result, ithas proven difficult to identify new treatments, biomarkersand meaningful strategies for stratifying treatment. A suc-cessful translational agenda in neuropsychiatry requiressolutions to this impasse. Two studies will be discussedwhich take different approaches to the problem. In the first,plasma samples taken from large case/control studies ofunipolar depression and schizophrenia were analysed using acommercially available platform. Patients were diagnosedaccording to DSM-IV criteria. Plasma samples from 245depressed patients, 229 schizophrenic patients and 267controls were selected for profiling of up to 78 proteins,including cytokines, chemokines and neurotrophins. Dataanalysis identified proteins which differed between cases andcontrols, such as insulin and MMP9 for depression; BDNF,EGF and a number of chemokines for schizophrenia. In thesecond study, an expression analysis of 30,000 mRNAtranscripts was conducted on post-mortem tissue fromBrodmann area 10 (anterior prefrontal cortex) taken from28 schizophrenic patients and 23 controls. Data were com-pared with those of an independent prefrontal cortex datasetfrom the Harvard Brain Bank. Fifty-one gene expressionchanges were identified that are common between theschizophrenia cohorts, and 49 show the same direction ofdisease-associated dysregulation. Changes were observed ingene sets associated with synaptic vesicle recycling, trans-mitter release and cytoskeletal dynamics, suggesting multi-ple, synergistic changes in gene expression that affect nerveterminal function. These findings potentially shed light onthe underlying pathophysiology of schizophrenia and de-pression and suggest new avenues for translational research.
Key words: schizophrenia; unipolar depression; mRNA;BA 10; biomarker; protein
DIET RESTRICTION AND DIET RESTRICTION MIMETICS: ANANTI-AGING STRATEGY FOR CANINES?D.K. Ingram1,*, G.S. Roth2
1Pennington Biomedical Research Center, LSU System,6400 Perkins Road, Baton Rouge, LA, 708082GeroScience, Inc., Pylesville, MD, 21132*Corresponding author: [email protected]
Reducing intake of a nutritious diet by 20-50% can increaselifespan, reduce incidence and retard onset of chronicdiseases, enhance stress protection, and maintain youthfulfunction. This paradigm, known as diet restriction (DR),has proven to be the most robust means to retard aging asdemonstrated in numerous species, but its application tohuman or companion animal aging represents a challenge.One DR study completed in Labrador retrievers hasreported increased lifespan, reduced disease, and improvedfunction. Reports of people who practice DR and fromclinical studies also indicate such regimens can positivelyaffect indices of health and risk factors for disease.Nonetheless, despite evidence that DR produces benefi-cial effects in humans and dogs, therapeutic applicationwould be problematic due to difficulties of complianceand other quality of life issues. To address this challenge,we introduced the concept of DR ‘‘mimetics’’ (DRM) as amethod to obtain ‘‘anti-aging’’ and health-promotingbenefits of DR without reducing food intake. Severalcandidate DRM compounds have been proposed includ-ing the sirtuin activator, resveratrol, and the insulinsensitizer, metformin, but neither candidate has shownreliable and consistent prolongevity effects. Followingour previous work with 2-deoxyglucose, we have beenexamining the anti-aging benefits of glycolytic inhibitionproduced by mannoheptulose (MH), a seven carbon sugarthat inhibits hexokinase. Preliminary results in severalanimal models, including dogs, indicate that a dietsupplemented with an avocado extract enriched withMH, has great potential as a DRM that can be used inhuman and pet applications.
Key words: aging; diet restriction; longevity; nutrition;glucose metabolism; avocado; mannoheptulose
MODELING ANXIETY IN BEAGLE DOGSC. de Rivera1,2,*, J.A. Araujo1,2, N.W. Milgram1,2
1CanCog Technologies Inc, 120 Carlton St., Suite 204,Toronto, ON, Canada2University of Toronto, Department of Pharmacology,Toronto, ON, Canada*Corresponding author: [email protected]
In humans, anxiety is a common emotion which can alsobe a manifestation of a neuropsychiatric disorder.Companion animals as well can show anxiety-likebehaviors which in some instances leads to highlymaladaptive behaviors, such as separation anxiety andfear of strangers. A better understanding of canine anxietyis potentially important both as providing a potentiallynew animal model of human anxiety, and to assist in thedevelopment of new therapeutics for treatment of anxietydisorders in companion animals. The goal of the currentpilot studies was to develop clinically relevant objectivelaboratory tests to evaluate therapeutic response of anx-iolytics. We sought first to distinguish in our laboratory
