COMPREHENSIVE NEUROAIDS CENTER (cnac)
Basic Science Core II: Animal Models, Behavioral Testing, Pathology, and Histology
This core assists researchers studying AIDS and brain disorders to utilize animal models for evaluating therapeutics and behavioral tests for improving treatments diagnosis and prevention. Moreover, this core provides services to researchers in analyzing human samples and animal tissues for improving diagnosis of disease and understanding the mechanisms involved in the pathogenesis of neuroAIDS.
We assist investigators in the development, analysis, and characterization of animal models with impaired nervous system function related to HIV-1 and AIDS, including phenotypic characterization of animals at the anatomical level and full-scale behavioral characterization of animals including memory, learning, and other cognitive functions, sensory and motor function, development and aging, neurological and neuromuscular assessment.
For additional information on animal models, please contact Jennifer Gordon, PhD.
For additional information on animal behavioral testing, please contact Mary Barbe, PhD.
We offer histological and immunohistochemical services for the evaluation of human autopsy and biopsy clinical samples, tissues harvested from experimental animal models, and cell cultures. More specifically, this core performs neuropathological evaluation of tissues from animal models and patients with neurological disorders including AIDS, PML, CNS neoplasia, and other neurodegenerative diseases, including peripheral neuropathies. Further, this core provides training in Laser Capture Microdissection (LCM) accessioning of tissue samples and nucleic acid extraction for downstream molecular biological applications, immunohistochemical labeling, photodocumentation, and quantitative analysis of neuronal density and expression of cellular and viral proteins using image analysis systems and methods. Through its microscope facilities, this core assists in training and use of the image capture and analysis techniques. In service hands-on training or seminars on core techniques are held from time to time. Please visit the CNAC website for upcoming sessions.
To schedule a neuropathology consultation, please email firstname.lastname@example.org. Consultations are available by appointment each week.
We are currently completing a series of histological and behavioral assays on mice heterozygous for the Pur-alpha protein, an essential protein for postnatal brain development that localizes specifically to dendrites. Mice lacking Pur-alpha display decreased neuronogenesis and impaired neuronal differentiation (Mishra et al 2013). Yet, the effects of the Pur-alpha induced brain changes on memory behavioral changes have yet to be explored in mice that are heterozygous for pur-alpha. Our histological data showed an increase in Pur-alpha immunostaining in the hippocampus, a key brain structure involved in memory processing. Therefore, we utilized two different object recognition memory assays, novel object-recognition and novel object-location tests, to determine if memory losses are occurring as a consequence of the increase in hippocampus Pur-alpha.
The object-recognition and object-location memory tasks are based on a rodent’s spontaneous tendency to explore novelty in their environment. In the object-recognition task, the exploration of a new object is compared with the exploration of a familiar object. In the object-location task, the ability to detect the displacement of familiar objects to new locations is assessed. The tasks consist of a familiarization session, in which rats encode the object information, then an acquisition session, in which rodents are supposed to retrieve the previous object information, detect the familiarity and react to changes [1, 2]. The two tasks of object memory recognition are then repeated after an retention interval, to further challenge the rodent’s ability to retrieve the previous object information. The object-recognition task implies the “ventral stream” or “what” pathway for the detection of visual information based on object features (i.e. shape, color, texture), which is mediated by the perirhinal cortex, lateral entorhinal cortex and lastly, the hippocampus [1, 2]. The object-location task seems to involve the “dorsal stream” or “where” pathway to process the spatial arrangement of objects. This pathway preferentially activates the postrhinal cortex, medial entorhinal cortex and finally, the hippocampus .
We used a 5 min interval to test short-term memory and 1 hour interval to test longer-term memory in a clear open field box, combined with digital camera tracking by AnyMaze software. The magnitude of the reaction to novelty was determined using a reaction ratio in which the mean duration of contacts with the “familiar” object was subtracted from the mean duration of contacts with the “new” object, and divided by the amount of time spent exploring the objects .
These reaction deficits may result from impairments in encoding object features and spatial configuration, or disturbances in both short-term and long-term memory, since the heterozygous Pur-alpha mice displayed degraded abilities to retrieve and discriminate familiar from new information in the environment. The memory deficits in the heterozygous Pur-alpha mice may result from damage to the ventral and dorsal streams involved in both information processing to extract object and spatial features, and memory. These results are encouraging in light of our histological results of changes in the hippocampus, and support further research in this area.
Jennifer Gordon, PhD
Mary F. Barbe, PhD
Basic Science Core II Co-Leader
Animal behavioral testing
Department of Anatomy and Cell Biology
Temple University School of Medicine
3500 N. Broad Street, 4th Fl. MERB