Comparison of methods for analysis of functional observation battery (FOB) data

The role of aluminum (Al) in Alzheimer disease is highly controversial. However, this element has been detected in neuritic plaques and neurofibrillary tangles in patients with Alzheimer disease. Its presence in neuritic plaques in hippocampus is especially relevant, as this is an area closely related to spatial learning and memory. In this study, the diet of wild-type and Tg2576 mice (animals overexpressing the human amyloid precursor protein) was supplemented with Al lactate (1 mg/g). General neurotoxic Al effects were evaluated using a functional observational battery and a novel object recognition task. Four experimental groups were used: Control-wild, Al-wild, Control-Tg, and Al-Tg mice. The results show a decreased home-cage activity and an increase in piloerection in all Al-exposed animals, and an increased sensorimotor reactivity in Tg2576 mice given Al. Neither Al treatment nor genotype had any noticeable effect on corticosterone levels and Al concentrations in frontal cortex and cerebellum of the mice. Recognition memory was impaired in Tg2576 mice, whereas β-amyloid plaque depositions were observed in all these animals. However, Al did not alter the recognition memory and β-amyloid plaque loads of Tg2576 mice.

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“…Bonferroni correction was used to account for multiple comparisons (MannWhitney U test). 33 Statistical significance was set at P < 0.05.…”

Section: Statisticsmentioning

confidence: 99%

Recognition Memory and β-amyloid Plaques in Adult Tg2576 Mice are not Modified After Oral Exposure to Aluminum

Ribes

Torrente

Vicens

et al. 2012

Alzheimer Disease &Amp; Associated Disorders

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“…A wide range of group sizes was reported (i.e. n=3 to 30), but a majority of respondents (Moscardo et al, 2007;Markgraf et al, 2010) to identify drug effects in FOB studies. Results from the current survey confirm that a majority of participants undertake statistical analysis (combined 74%), at least for some parameters.…”

Section: Discussionmentioning

confidence: 99%

“…Setting a lower threshold than this (ie, 3/6) is arguably prudent when in the business of hazard detection. Statistical analysis is more appropriate when using a larger group size and when ranking the severity of the observed parameters, but even so, when Markgraf et al (2010) Pharmacological effects identified during FOB may differ between adult and juvenile animals (Himmel, 2008), justifying careful designs supported by regulatory guidance documents (EMEA, 2008;FDA, 2006) to investigate possible neurotoxicity in a younger population when applicable. Authier et al 2015JPTM 6/2/2016 A wide range of approved drugs are associated with drug induced sleep disturbances such as insomnia, including beta-blockers (Chang et al, 2013;Moser, 1979), corticosteroids (Ciriaco et al, 2013), selective serotonin-reuptake inhibitors (SSRI) (Asnis, et al, 1999) or acetylcholinesterase inhibitors (Cooke et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Safety Pharmacology Investigations on the Nervous System: An Industry Survey

Authier

2017

Journal of Pharmacological and Toxicological Methods

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Abstract:The Safety Pharmacology Society (SPS) conducted an industry survey in 2015 to identify industry practices as they relate to central, peripheral and autonomic nervous system ("CNS") drug safety testing. One hundred fifty-eight (158) participants from Asia (16%), Europe (20%) and North America (56%) responded to the survey. 52% of participants were from pharmaceutical companies (>1,000 employees). Oncology (67%) and neurology/psychiatry (66%) were the most frequent target indications pursued by companies followed by inflammation (48%), cardiovascular (43%), metabolic (39%), infectious (37%), orphan (32%) and respiratory (29%) diseases. Seizures (67% of participants), gait abnormalities (67%), tremors (65%), emesis (56%), sedation (52%) and salivation (47%) were the most commonly encountered CNS issues in pre-clinical drug development while headache (65%), emesis/nausea (60%), fatigue (51%) and dizziness (49%) were the most frequent issues encountered in Phase I clinical trials. 54% of respondents reported that a standard battery of tests applied to screen drug candidates was the approach most commonly used to address nonclinical CNS safety testing. A minority (14% of all participants) reported using electroencephalography (EEG) screening prior to animal inclusion on toxicology studies. The most frequent group size was n=8 for functional observation battery (FOB), polysomnography and seizure liability studies. FOB evaluations were conducted in a dedicated room (78%) by blinded personnel (66%) with control for circadian cycle (55%) effects (e.g., dosing at a standardized time; balancing time of day across treatment groups). The rat was reported as the most common species used for seizure liability, nerve conduction and drug-abuse liability testing.

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“…After dermal irritation scoring, functional observational battery (FOB) was conducted to investigate gross functional deficits due to dermal exposure of extracts as described elsewhere. 37,38 Exploratory behavior in hole-board test Followed by FOB, the exploratory behavior was assessed using a holeboard apparatus in all treatment groups. This apparatus consisted of 40 cm square floor with 16 equally spaced holes of 3 cm diameter and mounted on four legs of 25 cm height.…”

Section: Functional Observational Battery (Fob)mentioning

confidence: 99%

Phytochemical, in vitro Antioxidant and in vivo Safety Evaluation of Leaf Extracts of Tragia plukenetii

Bonam¹,

Manoharan²,

Pandy³

et al. 2019

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Objective: To investigate the phytochemical properties, in vitro antioxidant and in vivo safety profile of leaf extracts of Tragia plukenetii (TP). Methods: TP leaves were obtained from the south part of India (Guntur District, Andhra Pradesh) and it was extracted with different solvents (Benzene Extract (BE), Chloroform Extract (CE) and methanolic extract (ME)). These TP extracts were analyzed for the in vitro antioxidant activity by DPPH reducing power, β-carotene-linoleic acid complex and iron chelation assays followed by in vivo acute oral and dermal toxicities using Swiss mice and Wistar rats respectively. Results: The present study results revealed ME exhibited an effective and powerful antioxidant activity when compared to a standard antioxidant, Butylated hydroxytoluene (BHT). ME was found to be effective in DPPH, β-carotene-linoleic acid complex and iron chelation assays respectively. In vivo acute oral toxicity study revealed that mice treated with up to 5000 mg/kg of BE, CE and ME did not show any signs of toxicity. Furthermore, similarly, acute dermal toxicity study demonstrated that BE, CE and ME did not exhibit any signs of dermal toxicity up to 1000 mg/kg in rats. Conclusion: TP extracts possess an excellent antioxidant activity with a devoid of any signs of acute oral and dermal toxicities.

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Comparison of methods for analysis of functional observation battery (FOB) data

Cited by 13 publications

References 17 publications

Recognition Memory and β-amyloid Plaques in Adult Tg2576 Mice are not Modified After Oral Exposure to Aluminum

Recognition Memory and β-amyloid Plaques in Adult Tg2576 Mice are not Modified After Oral Exposure to Aluminum

Safety Pharmacology Investigations on the Nervous System: An Industry Survey

Phytochemical, in vitro Antioxidant and in vivo Safety Evaluation of Leaf Extracts of Tragia plukenetii

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