Dataset Information

Non-spatial pre-training in the water maze as a clinically relevant model for evaluating learning and memory in experimental TBI.

ABSTRACT: Explicit and implicit learning and memory networks exist where each network can facilitate or inhibit cognition. Clinical evidence suggests that implicit networks are relatively preserved after traumatic brain injury (TBI). Non-spatial pre-training (NSPT) in the Morris Water Maze (MWM) provides the necessary behavioral components to complete the task, while limiting the formation of spatial maps. Our study utilized NSPT in the MWM to assess implicit and explicit learning and memory system deficits in the controlled cortical impact (CCI) model of TBI. 76 adult male Sprague-Dawley rats were divided: CCI vs. sham surgery, NSPT vs. No-NSPT, and cued vs. non-cued groups. NSPT occurred for 4d prior to surgery (dynamic hidden platform location, extra-maze cues covered, static pool entry point). Acquisition (d14-18), Probe/Visible Platform (d19), and Reversal (d20-21) trials were conducted with or without extra-maze cues. Novel time allocation and search strategy selection metrics were utilized. Results indicated implicit and explicit learning/memory networks are distinguishable in the MWM. In the cued condition, NSPT reduced thigmotaxis, improved place learning, and largely eliminated the apparent injury-induced deficits typically observed between untrained CCI and sham rats. However, among NSPT groups, incorporation of cues into search strategy selection for CCI rats was relatively impaired compared to shams. Non-cued condition performance showed sham/NSPT and CCI/NSPT rats perform similarly, suggesting implicit memory networks are largely intact 2weeks after CCI. Place learning differences between CCI/NSPT and sham/NSPT rats more accurately reflect spatial deficits in our CCI model compared to untrained controls. These data suggest NSPT as a clinically relevant construct for evaluating potential neurorestorative and neuroprotective therapies. These findings also support development of non-spatial cognitive training paradigms for evaluating rehabilitation relevant combination therapies.

SUBMITTER: Wagner AK

PROVIDER: S-EPMC3851771 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Non-spatial pre-training in the water maze as a clinically relevant model for evaluating learning and memory in experimental TBI.

Wagner Amy K AK Brayer Samuel W SW Hurwitz Max M Niyonkuru Christian C Zou Huichao H Failla Michelle M Arenth Patricia P Manole Mioara D MD Skidmore Elizabeth E Thiels Edda E

Neurobiology of learning and memory 20130718

Explicit and implicit learning and memory networks exist where each network can facilitate or inhibit cognition. Clinical evidence suggests that implicit networks are relatively preserved after traumatic brain injury (TBI). Non-spatial pre-training (NSPT) in the Morris Water Maze (MWM) provides the necessary behavioral components to complete the task, while limiting the formation of spatial maps. Our study utilized NSPT in the MWM to assess implicit and explicit learning and memory system defici ...[more]

PMID: 23871745

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Project description:STUDY QUESTION:Does spontaneous endometriosis in cynomolgus monkeys have the characteristics required of a good experimental model? SUMMARY ANSWER:Spontaneous endometriosis in cynomolgus monkeys exhibited similar clinicopathological characteristics to the human disease and was useful as an experimental model. WHAT IS KNOWN ALREADY:The prevalence of endometriosis in autopsied cynomolgus monkeys (Macaca fascicularis) in a breeding colony was reported to be 28.7% in 1993. The histopathological findings we reported recently showed that components of spontaneous endometriosis were not only endometriotic epithelium and stromal cells (CD10-positive) with hemorrhage and inflammation, but also smooth muscle metaplasia and nerve fibers. STUDY DESIGN, SIZE, DURATION:During routine medical examinations at a research facility from 2008 to 2012, 614 female cynomolgus monkeys of reproductive age (6-25 years) were screened for endometriosis by the presence of regular menstrual bleeding, serum CA125 levels and palpation of the abdomen. In total, 29 monkeys were selected as subjects for the following study. PARTICIPANTS/MATERIALS, SETTING, METHODS:Of the 29 monkeys selected, 15 were diagnosed with endometriosis by laparoscopy and/or open surgery. The monkeys were monitored by observing their general condition, and eight of these were monitored using laparoscopy and MRI. In addition, to investigate appropriate screening parameters and endometriosis-associated biological parameters in monkeys, we retrospectively examined general laboratory parameters that correlate to the menstrual cycle and disease status. MAIN RESULTS AND THE ROLE OF CHANCE:The combination of CA125 serum levels (this was a useful marker for chocolate cysts), palpation of the abdomen, and fecal abnormalities was the most efficient screening method for diagnosing monkeys with endometriosis. Each animal could be diagnosed and assigned a disease stage by laparoscopy. While monitoring the disease stage by laparoscopy and/or MRI, disease status in individual monkeys was mainly stable or was progressive for 2-7 months. The detection rate by screening was low (15/614) but age-specific analysis suggests that screening would be more efficient if a colony for an endometriosis model is maintained with 11-20-year olds. As an endometriosis-associated biological parameter, the decrease in food consumption that coincided with menstruation was selected and correlated well (R2 value = 0.8239) with disease status (according to a modified adhesion revised American Fertility Society score). LARGE SCALE DATA:N/A. LIMITATIONS, REASONS FOR CAUTION:Peritoneal fluid was not analyzed because a smaller amount is produced in cynomolgus monkeys than in baboons. Although clinical endometriosis-associated pain is evaluated in women using a visual analog scale, pain could not be directly evaluated in this non-human primate model. WIDER IMPLICATIONS OF THE FINDINGS:Although cynomolgus monkeys are relatively small (2-5 kg) primates, laparoscopy and MRI make it possible to evaluate spontaneous endometriosis in these monkeys and to monitor its development over time. Spontaneous endometriosis in cynomolgus monkeys is a useful model for evaluating disease progress and drug efficacy because they have similar lesions to those in humans, and conventional laboratory methods and parameters for assessment are well established. STUDY FUNDING/COMPETING INTEREST(S):No external funds were used for this study. A.N.-K., K.T., H.T., A.K. and M.S. are full-time employees of Chugai Pharmaceutical Co., Ltd. R.K. received a consultancy fee from Chugai Pharmaceutical Co., Ltd. and lecture fees from Chugai Pharmaceuticals, Japan Vaccine Co. Ltd., Merck & Co., Mochida Co. Ltd., Roche Diagnostics, and BD, unrelated to the submitted work. S.N., S.O. and T.S. have nothing to declare.

Dataset Information

Non-spatial pre-training in the water maze as a clinically relevant model for evaluating learning and memory in experimental TBI.

Publications

Non-spatial pre-training in the water maze as a clinically relevant model for evaluating learning and memory in experimental TBI.

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