Grooming Behavior Research Articles

Group A streptococcal antigen exposed rat model to investigate neurobehavioral and cardiac complications associated with post-streptococcal autoimmune sequelae.

BackgroundThe neuropsychiatric disorders due to post‐streptococcal autoimmune complications such as Sydenham's chorea (SC) are associated with acute rheumatic fever and rheumatic heart disease (ARF/RHD). An animal model that exhibits characteristics of both cardiac and neurobehavioral defects in ARF/RHD would be an important adjunct for future studies. Since age, gender, strain differences, and genotypes impact on the development of autoimmunity, we investigated the behavior of male and female Wistar and Lewis rat strains in two age cohorts (<6 weeks and >12 weeks) under normal husbandry conditions and following exposure to group A streptococcus (GAS).MethodsStandard behavioral assessments were performed to determine the impairments in fine motor control (food manipulation test), gait and balance (beam walking test), and obsessive‐compulsive behavior (grooming and marble burying tests). Furthermore, electrocardiography, histology, and behavioral assessments were performed on male and female Lewis rats injected with GAS antigens.ResultsFor control Lewis rats there were no significant age and gender dependent differences in marble burying, food manipulation, beam walking and grooming behaviors. In contrast significant age‐dependent differences were observed in Wistar rats in all the behavioral tests except for food manipulation. Therefore, Lewis rats were selected for further experiments to determine the effect of GAS. After exposure to GAS, Lewis rats demonstrated neurobehavioral abnormalities and cardiac pathology akin to SC and ARF/RHD, respectively.ConclusionWe have characterised a new model that provides longitudinal stability of age‐dependent behavior, to simultaneously investigate both neurobehavioral and cardiac abnormalities associated with post‐streptococcal complications.

DNA Methyltransferase Inhibitor Successfully Treats Obsessive-Compulsive Disorder in Various Mouse Models

Mental health disorders are manifested in families yet cannot be fully explained by classical Mendelian genetics. Changes in gene expression via epigenetics present a plausible mechanism. Anxiety often leads to avoidant behaviours, which upon repetition may become habitual, maladaptive, and resistant to extinction as observed in obsessive-compulsive disorders (OCD). Psychophysical models of OCD propose that anxiety (amygdala) and habits (dorsolateral striatum, DLS) may be causally linked. The amygdala activates spiny projection neurons in the DLS. Repetitive amygdala terminal stimulation in the DLS elicits long-term OCD-like behaviour in mice associated with circuitry changes and gene methylation-mediated decrease in protein phosphatase 1 (PP1). Treatment of OCD-like grooming behaviour in Slitrk5, SAPAP3, and laser-stimulated mice with one dose of RG108 (DNA methyltransferase inhibitor), leads to marked symptom improvement lasting for at least one week as well as a complete reversal of abnormal changes in the circuitry and PP1 activity.

The anxiolytic effect of some plant extracts in clinical trials and animal models

The phenomenon of anxiety remains poorly understood and there is much to be learnt about its’s effective treatment. Here we discuss the data of available scientific literature concerning the use of plant derived extracts in the treatment of anxiety. Study of the treating effects of natural alternatives to prescription drugs is very important in regard to limitations of current drug therapies. Significance of the study of treating efficacy of endemic plant species, endemic to Georgia in particular, and the use of animal models, such as rat grooming and rat behavior in maze, for evaluation of the anxiolytic efficacy of phytomedicines is discussed as well. We conclude, that medical as well as experimental trials in animal models of anxiety provide strong argument for the use of plant extracts as an alternative to the current drug therapies for anxiety.

Per- and polyfluoroalkyl substances (PFASs) in Swedish household dust and exposure of pet cats

Per- and polyfluoroalkyl substances (PFASs) are used in a wide range of products and have been found ubiquitously in our indoor environment, and there is evidence that exposure to PFAS can lead to adverse endocrine effects, such as thyroid hormone disruption. Pet cats have a high dust intake due to their grooming behavior and have been shown to be a suitable sentinel species for assessment of toddler’s exposure. Here we used paired household dust (n=46) and cat serum (n=27) samples to establish whether dust is a relevant exposure pathway to PFASs. An analytical method for PFAS analysis was optimized using a low volume of cat serum samples, combining solid-phase extraction and online sample cleanup. Dust was extracted with methanol by sonication and cleaned up by addition of active carbon. In total, 27 PFASs were analyzed by liquid chromatography/mass spectrometry analysis. The correlation between PFAS levels in dust and serum, serum lipids and thyroid hormone levels, and PFAS levels in dust between different rooms were statistically evaluated. PFOS and PFDA could be quantified in all cat serum samples (median 2300 pg/mL and 430 pg/mL, respectively), followed by PFOA (median 1100 pg/mL), quantified in 96% of the samples. The levels of 6:2 and 8:2 diPAPs were determined in 65% and 92% of the serum samples, respectively, and were an order of magnitude lower (1.4–160 pg/mL). Household dust on the other hand was dominated by 6:2 and 8:2 diPAPs, with a median of 65 ng/g dust and 49 ng/g dust, respectively. PFOS (median 13 ng/g dust) and PFOA (median 9 ng/g dust) were quantified in 93% of the dust samples. Only eight PFASs were detected (>LOD) in at least 50% of the samples of both matrices and could be paired. Significant correlations between cat serum and dust were found for PFOA (rS=0.32, p<0.049) and PFUnDA (rS=0.55, p<0.001). Significant positive correlations were found between serum total thyroxine (rS=0.11, p<0.05) and PFNA and between serum cholesterol and PFHpA (rS=0.46, p<0.01), PFUnDA (rS=0.40, p<0.05), PFDoDA (rS=0.44, p<0.01), and sum PFAS (rS=0.48, p<0.01). In conclusion, this study confirmed that dust is a relevant exposure pathway for the ingestion of some PFASs for cats, and the serum levels of PFASs could be of relevance for the cat’s health.

Effects of Aqueous Extract of Lycopersicum esculentum L. var. "Camone" Tomato on Blood Pressure, Behavior and Brain Susceptibility to Oxidative Stress in Spontaneously Hypertensive Rats.

Behavioral disorders affect millions of people worldwide. Hypertension contributes to both the development and progression of brain damage and cognitive dysfunction and could represent the most powerful modifiable risk factor for cerebral vessel dysfunction and consequent behavioral impairment. Tomato contains antioxidants and bioactive molecules that might play an important role in the prevention of cardiovascular and brain diseases. The effects of the combined gel and serum from Lycopersicum esculentum L. var. “Camone” tomatoes and those of purified tomato glycoalkaloids (tomatine) and an antihypertensive drug (captopril) were investigated in male spontaneously hypertensive rats (SHRs) and compared with normotensive Wistar Kyoto (WKY) rats. Body weight, systolic blood pressure, behavioral parameters, as well as brain susceptibility to oxidative stress and brain cytokine contents, were assessed. Treating hypertensive rats with tomato gel/serum or captopril for four weeks caused a significant reduction in blood pressure, decreased locomotor activity and increased grooming behavior; the last two parameters were also significantly affected by tomatine treatment. Brain slices obtained from hypertensive rats treated with tomato gel/serum were more resistant to oxidative stress and contained lower levels of inflammatory cytokines than vehicle-treated ones. In contrast, tomatine treatment had no effect. In conclusion, the tomato-derived gel/serum can be considered a dietary supplement able to drive in vivo blood pressure towards healthier values and also control some central effects such as behavior and brain oxidative stress.

Action detection using a neural network elucidates the genetics of mouse grooming behavior.

Automated detection of complex animal behaviors remains a challenging problem in neuroscience, particularly for behaviors that consist of disparate sequential motions. Grooming is a prototypical stereotyped behavior that is often used as an endophenotype in psychiatric genetics. Here, we used mouse grooming behavior as an example and developed a general purpose neural network architecture capable of dynamic action detection at human observer-level performance and operating across dozens of mouse strains with high visual diversity. We provide insights into the amount of human annotated training data that are needed to achieve such performance. We surveyed grooming behavior in the open field in 2457 mice across 62 strains, determined its heritable components, conducted GWAS to outline its genetic architecture, and performed PheWAS to link human psychiatric traits through shared underlying genetics. Our general machine learning solution that automatically classifies complex behaviors in large datasets will facilitate systematic studies of behavioral mechanisms.

Silencing of selenium-binding protein disrupted the active immunization of the termite Reticulitermes chinensis and improved the lethal effect of the entomopathogenic fungus Metarhizium anisopliae

Active immunization is a process by which naïve termites receive sublethal doses of pathogenic spores from infected termites through social contact to enhance their immune responses; this process significantly diminishes the termite biocontrol effect of commercial entomopathogenic products, such as Metarhizium anisopliae. We found that the expression of selenium-binding protein (SeBP) was significantly increased by active immunization of the nestmates of fungus-contaminated termites, suggesting a close relationship between SeBP and active immunization in termites. To elucidate this relationship, we used the fungus M. anisopliae to contaminate the termite Reticulitermes chinensis and then measured the changes in the grooming behavior, antifungal activity, immune gene expression and survival of the double-stranded SeBP (dsSeBP)-injected nestmates of these fungus-contaminated termites. Our results showed that there was no significant change in the grooming behavior of the dsSeBP-injected nestmates of the fungus-contaminated termites, but the antifungal activity and expression of the immune gene Gram-negative bacteria-binding protein 2 (GNBP2) were significantly reduced. Moreover, the survival of the dsSeBP-injected nestmates of the fungus-contaminated termites was significantly decreased. These findings showed that SeBP knockdown disrupted the active immunization of R. chinensis and improved the lethal effect of M. anisopliae, which suggested that enhancing immune dysregulation by targeting SeBP was a sound strategy for the biological control of termites.

A nutty idea: Exploring a novel method using a hazelnut cocoa spread to temporarily increase maternal care behavior within a rat litter.

Maternal care plays a crucial role for infant development. In humans, skin-to-skin care is often used for preterm infants to reduce acute stress and improve long-term developmental outcome. Here we propose a new translational approach to study the effects of acute increases in maternal care on offspring development in rodents. First, pilot studies determined that dams spent more time licking pups covered in hazelnut cocoa spread (Nutella® )) than any other studied substance. For the main experiment, Sprague-Dawley rats were bred in-house, and Nutella® was applied four times a day to treatment pups (2 males/females per litter) of seven litters from PN2 to 5. Control pups (2 males/females per litter) were handled similarly without applying any substance. Maternal licking and grooming behavior was observed for 30min following each Nutella® application. Nutella® -covered pups received significantly more licking and grooming compared to control pups within each litter. There was no difference in body weight or basal serum corticosterone levels between Nutella® -covered and control pups on PN5, suggesting that the Nutella® application and subsequent increased maternal licking was not stressful for the pups. Future studies will investigate whether this increase in maternal care can protect pups from stress- or pain-induced rises in corticosterone.

Expression of Human Immunodeficiency Virus Transactivator of Transcription (HIV-Tat1-86) Protein Alters Nociceptive Processing that is Sensitive to Anti-Oxidant and Anti-Inflammatory Interventions.

Despite the success of combined antiretroviral therapy (cART) in reducing viral load, a substantial portion of Human Immunodeficiency Virus (HIV)+ patients report chronic pain. The exact mechanism underlying this co-morbidity even with undetectable viral load remains unknown, but the transactivator of transcription (HIV-Tat) protein is of particular interest. Functional HIV-Tat protein is observed even in cerebrospinal fluid of patients who have an undetectable viral load. It is hypothesized that Tat protein exposure is sufficient to induce neuropathic pain-like manifestations via both activation of microglia and generation of oxidative stress. iTat mice conditionally expressed Tat(1-86) protein in the central nervous system upon daily administration of doxycycline (100 mg/kg/d, i.p., up to 14 days). The effect of HIV-Tat protein exposure on the well-being of the animal was assessed using sucrose-evoked grooming and acute nesting behavior for pain-depressed behaviors, and the development of hyperalgesia assessed with warm-water tail-withdrawal and von Frey assays for thermal hyperalgesia and mechanical allodynia, respectively. Tissue harvested at select time points was used to assess ex vivo alterations in oxidative stress, astrocytosis and microgliosis, and blood-brainbarrier integrity with assays utilizing fluorescence-based indicators. Tat protein induced mild thermal hyperalgesia but robust mechanical allodynia starting after 4 days of exposure, reaching a nadir after 7 days. Changes in nociceptive processing were associated with reduced sucrose-evoked grooming behavior without altering acute nesting behavior, and in spinal cord dysregulated free radical generation as measured by DCF fluorescence intensity, altered immunohistochemical expression of the gliotic markers, Iba-1 and GFAP, and increased permeability of the blood-brainbarrier to the small molecule fluorescent tracer, sodium fluorescein, in a time-dependent manner. Pretreatment with the anti-inflammatory, indomethacin (1 mg/kg/d, i.p.), the antioxidant, methylsulfonylmethane (100 mg/kg/d i.p.), or the immunomodulatory agent, dimethylfumarate (100 mg/kg/d p.o.) thirty minutes prior to daily injections of doxycycline (100 mg/kg/d i.p.) over 7 days significantly attenuated the development of Tat-induced mechanical allodynia. Collectively, the data suggests that even acute exposure to HIV-1 Tat protein at pathologically relevant levels is sufficient to produce select neurophysiological and behavioral manifestations of chronic pain consistent with that reported by HIV-positive patients.

Students’ accounts of grooming and boundary-blurring behaviours by academic staff in UK higher education

ABSTRACT Drawing on data from qualitative interviews with students who had attempted to report staff sexual misconduct to their higher education institutions in the UK, the article analyses interviewees’ experiences of ‘grooming’ and boundary-blurring behaviours from academic staff where the possibility for consent was affected by the power imbalances between staff and students. The term ‘boundary-blurring’ is used to describe behaviours that transgress (often tacit) professional boundaries, and ‘grooming’ refers to a pattern of these behaviours over time between people in positions of unequal power. This article analyses the power imbalances interviewees described that created the context for these behaviours. These were constituted by social inequalities including gender, class, and age, as well as stemming from students’ position within their institutions. The article also explores how heterosexualised normativity allows such behaviours to be minimised and invisibilised.

Machine learning algorithms for lamb survival

Lamb survival is influenced by the culmination of a sequence of often interrelated events including genetics, physiology, behaviour and nutrition, with the environment providing an overarching complication. Machine learning algorithms offer great flexibility with regard to problems of complex interactions among variables. The objective of this study was to use machine learning algorithms to identify factors affecting the lamb survival in high altitudes and cold climates. Lambing records were obtained from three native breed of sheep (Awassi = 50, Morkaraman = 50, Tuj = 50) managed in semi intensive systems. The data set included 193 spring born lambs out of which 106 lambs were sired by indigenous rams (n = 10), and 87 lambs were sired by Romanov Rams (n = 10).Factors included were dam body weight at lambing, age of dam, litter size at birth, maternal and lamb behaviors, and lamb sex. Individual and cohort data were combined into an original dataset containing 1351 event records from 193 individual lambs and 750 event records from 150 individual ewes. Classification algorithms applied for lamb survival were Bayesian Methods, Artificial Neural Networks, Support Vector Machine and Decision Trees. Variables were categorized for lamb survival, lamb behavior, and mothering ability. RandomForest performed very well in their classification of the mothering ability while SMO was found best in predicting lamb behavior. REPtree tree visualization showed that grooming behavior is the first determinant for mothering ability. Classification Trees performed best in lamb survival. Our results showed that Classification Trees clearly outperform others in all traits included in this study.

Variation of cleaning organ structures and setae of pedipalp tarsus in the family Phrynidae (Arachnida: Amblypygi)

The pedipalp tarsus of Amblypygi is used as a cleaning tool in grooming behavior and as a weapon in prey capture. The tarsus presents several structures with unknown functions that probably relate to both processes. The Amblypygi tarsus possesses a cleaning organ with two lines of projections and a group of setae distributed along the structure. We analyzed the morphological variation of the cleaning organ structures and the setae of the tarsus in species of the family Phrynidae using scanning electron microscopy (SEM). Additionally, we made histological sections to evaluate the sensory function of the structures. We found variation in the shape and size of the setae, projections and granular area of the cleaning organ; however, the observed differences do not allow for differentiation of taxonomic genera. The setae and projections of the cleaning organ have an internal structure similar to tip-pore sensilla. Externally, the setae are similar to the sensorial hairs in spiders and differ from the cleaning organ projections, which probably are modified setae. Mechanoreception function is evident in the setae, and is probable in projections of the cleaning organ; the evidence observed indicates that both structures may be considered as putative chemoreceptors.

Audiovisual overstimulation in childhood and adolescence promotes hyperactive behaviour in adult mice

There is a discussion about the impact of technological development on behavioural aspects, a nuance that the present study aimed to assess. p21, p26 and p36 mice were subjected to audio (70 db) and visual stimulation (flashing lights) for 2 or 6 h per day until p64. Naive animals were included. From p74 onwards, the animals were subjected to tests to assess their locomotion, depression, anxiety, aggressiveness, and nociception behaviours. Weight assessment was also performed. The animals that received stimulation for 2 h a day since p21 showed a decrease in rearing and grooming behaviour in the open field test, as well as in the mechanical orofacial sensitivity. Animals that received stimulation for 6 h daily since p21 showed increased locomotor activity in the open field test. Animals that received stimulation for 2 h a day since p26 showed an increase in locomotor activity and a decrease in grooming behaviour in the open field test, in addition to a reduction in the number of entries in the closed arm of the elevated plus maze. Animals stimulated from p26 for 6 h daily increased the reaction time to the thermal stimulus. Animals that received stimulation for 2 h daily since p36 showed an increase in locomotor activity and a decrease in grooming behaviour in the open field test. Taken together, these findings suggest that audiovisual overstimulation during critical periods of brain development may have adverse effects compatible with hyperactivity in adulthood.

Simple approaches for environmental and mechanical management of the Varroa mite, Varroa destructor Anderson and Trueman (Parasitiformes: Varroidae), on the honey bee, Apis mellifera L. (Hymenoptera: Apidae) in Egypt

BackgroundVarroa mite, Varroa destructor Anderson and Trueman (Parasitiformes: Varroidae), is an ectoparasitic mite of the honey bee, Apis mellifera L. (Hymenoptera: Apidae), with a great economic importance. It is the major deadlock of apiculture development all over the world.ResultsThis work aimed to assess the effect of bee house and dark bee house on numbers of Varroa mite on white card board sheets, worker broods, and alive bees during spring and autumn of 2018 and 2019. Two types of card board for sticking the fallen Varroa mite were evaluated through winter of 2019. Keeping honey bee hives in a dark room during March and September of 2018 and 2019 for a successive 3 days resulted in a great reduction in the number of Varroa inner bee hive, i.e., on the white card board sheets, area of broods, and alive honey bee. Highest number of fallen Varroa mite on the white card board sheets was obtained in the case of using the dark bee house during March and September in 2018 and 2019, followed by keeping in a normal bee house then those fallen in the case of the open apiary.ConclusionThe dark bee house grooming behaviour increased through 3 days of dark. Environmental management of bee house and dark bee house can be promising in colony collapse disorder. Modified adhesive sheets were more efficient in this regard than the normal ones.

Social contagion of affiliation in female macaques.

Social contagion of non-interactive behaviour is widespread among animals including humans. It is thought to facilitate behavioural synchronization and consequently group cohesion, coordination and opportunities for social learning. Contagion of interactive behaviour—particularly affiliation—has received much less attention. Here, we investigated in female rhesus macaques (Macaca mulatta) the effect of observing group members groom on a subject's subsequent grooming behaviour and the potential modulation of contagion by relationship quality and social status. We recorded behaviour after subjects witnessed a grooming event and compared it to behaviour in a control condition with the same individuals in proximity but in the absence of a stimulus grooming event. Compared to the control condition, after observing others groom, females engaged in a grooming interaction sooner, and were more likely to be the initiator and to take on the active groomer role. Dominance rank of the focal individual and more weakly also of the stimulus individuals affected the latency to the next grooming interaction of the focal subject. Latency to the next grooming interaction decreased with increasing rank of the subject potentially reflecting lower social constraints faced by high ranking individuals in this highly despotic species. Relationship quality between the subject and the stimulus individuals had no effect on latency to grooming. Collectively, our findings provide evidence for visual contagion of affiliation in rhesus macaques. Future studies should explore the systematic variation in contagion of interactive behaviour in relation to a gradient of social tolerance.

Temporal Order of Neural Progenitor Division Controls Neural Connectivity

Spatiotemporal mechanisms generating neural diversity are fundamental for understanding neural processes. Here, we investigated how neural connection diversity arises from neurons coming from identical progenitors. In the dorsal thorax of Drosophila, rows of mechanosensory organs originate from the division of sensory organ progenitor (SOPs). We show that in each row of the notum, a central SOP divides first, then neighboring SOPs divide, and so on. This centrifugal wave of mitoses depends on cell-cell inhibitory interactions mediated by SOP cytoplasmic protrusions and Scabrous, a secreted protein interacting with the Delta/Notch complex. When scabrous was downregulated, the mitotic wave was abolished, axonal growth was more synchronous, axonal terminals had a complex branching pattern and fly behavior was impaired. We propose that the temporal order of progenitor divisions influences the birth order of sensory neurons which is critical for correct axon wiring and appropriate grooming behavior, supporting the idea that developmental timing controls neural connectivity.

Environmental Enrichment Ameliorates Psychological Dependence Symptoms and Voluntary Morphine Consumption in Morphine Withdrawn Rats Under Methadone Maintenance Treatment

Introduction:Previous studies have shown that physical and psychological dependence and the vulnerability to relapse are still present during MMT. Thus, this study examined whether Enriched Environment (EE) would attenuate anxiety, depressive, and obsessive-compulsive-like behaviors, as well as voluntary morphine consumption following Methadone Maintenance Treatment (MMT) in morphine withdrawn rats.Methods:The rats were injected bi-daily doses (10 mg/kg, 12-h interval) of morphine for 14 days. Then, the rats were reared in a Standard Environment (SE) or EE for 30 more days during morphine withdrawal, simultaneous with receiving MMT. The rats were tested for anxiety (the Elevated Plus Maze [EPM]) and depression (Sucrose Preference Test [SPT]), Obsessive-Compulsive Disorder (OCD) as grooming behavior, and voluntary morphine consumption using a Two-Bottle Choice (TBC) paradigm.Results:The findings revealed that EE experience in morphine withdrawn rats under MMT significantly increased the EPM open-arm time and higher sucrose preference than SE rats. Also, we found that the EE decreased the self-grooming behavior and morphine preference ratio in morphine withdrawn rats receiving MMT compared to the SE group.Conclusion:We conclude that exposure to EE decreased methadone-induced anxiety, depressive and OCD-like behaviors, and voluntary morphine consumption in morphine withdrawn rats under MMT. Thus, the EE seems to be one of the strategies for reducing MMT-induced behavioral dysfunction and the risk of relapse induced by morphine withdrawal.

The profile of dexamethasone combined with transcranial direct current stimulation in rats submitted to an arthritis model

ABSTRACT BACKGROUND AND OBJECTIVES: To pursue safer and more effective treatments for rheumatoid arthritis, the effect of dexamethasone treatment (DEX, 0.25mg/kg) combined with transcranial direct current stimulation (tDCS) in the behavior and neurochemical parameters of arthritic rats was evaluated. METHODS: Thirty-six Wistar rats were divided into four groups: control+DEX (CTRL+DEX), arthritis+DEX (RA+DEX), arthritis+DEX+sham-tDCS (RA+DEX+sham-tDCS) and arthritis+DEX+tDCS (RA+DEX+tDCS). The arthritic model (RA) was induced by complete Freund’s adjuvant (CFA) paw administration. Paw edema and mechanical allodynia were assessed by plethysmometer and von Frey apparatus, respectively. Fourteen days after the CFA injection, rats received the treatment for eight days (DEX and/or tDCS). Behavioral parameters were measured with the Open-Field test. ELISA was used to evaluate hippocampal and spinal cord tumor necrosis factor (TNF-α) levels, cerebral cortex and brainstem BDNF levels. RESULTS: In pre-treatment measurements, arthritic rats presented an increase in joint swelling and mechanical allodynia when compared to the control group, confirming chronic pain establishment. A slight antinociceptive effect of dexamethasone combined with tDCS in the pain model was observed. The pain model significantly induced an increase in the grooming behavior and a reduction in the spinal cord and hippocampal TNF-α levels; these effects were reverted in the sham- and active-tDCS-treated rats. However, no effects of DEX or tDCS were observed in the BDNF levels in the cerebral cortex and brainstem. CONCLUSION: Despite the small effect observed, tDCS treatment cannot be discarded as a non-pharmacological adjuvant technique for inflammatory chronic pain treatment.

Ouabain induces memory impairment and alter the BDNF signaling pathway in an animal model of bipolar disorder: Cognitive and neurochemical alterations in BD model

BackgroundThe present study aims to evaluate the effects of ouabain on memory and neurotrophic parameters in the brains of rats. MethodsWistar rats received an intracerebroventricular (ICV) injection of ouabain or artificial cerebrospinal fluid (aCSF). Seven and 14 days after ICV administration, the animals were subjected to the open-field and splash tests. Furthermore, the pro-BDNF, BDNF, TrkB, and CREB were assessed in the frontal cortex and hippocampus of the rats, in both seven and 14 days after ICV injection. The memory of the animals was tested by novel object recognition test (NOR) and inhibitory avoidance task (IA), only 14 days after ICV administration. ResultsOuabain increased locomotion and exploration in the animals seven days after its administration; however, 14 days after ICV, these behavioral parameters return to the basal level. Seven days after ouabain administration increased grooming behavior in the splash test; on the other hand, seven days after ouabain injection decreased the grooming behavior, which is considered an anhedonic response. Besides, ouabain decreased recognition index in the NOR and decreased aversive memory in the IA, when compared to the control group. The levels of pro-BDNF and BDNF decreased in the frontal cortex seven days after ouabain; but its receptor (TrkB) and CREB decreased seven and 14 days after ouabain, in both cerebral structures evaluated. ConclusionOuabain-induced animal model of BD is an excellent model to assess memory alteration, observed in bipolar patients. Besides, the memory impairment induced by ouabain seems to be related to BDNF signaling pathway alterations.

The Putative Role of 1,25(OH)2D3 in the Association of Milk Consumption and Parkinson's Disease.

The consumption of dairy products, particularly of low fat milk, has been shown to be associated with the occurrence of Parkinson's disease. This association does not necessarily reflect a pathophysiological role of milk intake in the development of Parkinson's disease. Nevertheless, the present review discusses a potential mechanism possibly mediating an effect of milk consumption on Parkinson's disease. The case is made that milk is tailored in part to support bone mineralization of the suckling offspring and is thus rich in calcium and phosphate. Milk intake is thus expected to enhance intestinal calcium phosphate uptake. As binding to fatty acids impedes Ca2+ absorption, low fat milk is particularly effective. Calcium and phosphate uptake inhibit the formation of 1,25(OH)2D3 (1,25-dihydroxy-vitamin D3 = calcitriol), the active form of vitamin D. Calcium inhibits 1,25(OH)2D3 production in part by suppressing the release of parathyroid hormone, a powerful stimulator of 1,25(OH)2D3 formation. Phosphate excess stimulates the release of fibroblast growth factor FGF23, which suppresses 1,25(OH)2D3 formation, an effect requiring Klotho. 1,25(OH)2D3 is a main regulator of mineral metabolism, but has powerful effects apparently unrelated to mineral metabolism, including suppression of inflammation and influence of multiple brain functions. In mice, lack of 1,25(OH)2D3 and excessive 1,25(OH)2D3 formation have profound effects on several types of behavior, such as explorative behavior, anxiety, grooming and social behavior. 1,25(OH)2D3 is produced in human brain and influences the function of various structures including substantia nigra. In neurons 1,25(OH)2D3 suppresses oxidative stress, inhibits inflammation and stimulates neurotrophin formation thus providing neuroprotection. As a result, 1,25(OH)2D3 is considered to favorably influence the clinical course of Parkinson's disease. In conclusion, consumption of milk could in theory accelerate the downhill course of neuronal function in Parkinson's disease. However, substantial additional experimentation is required to define the putative causal role of 1,25(OH)2D3 in the pathophysiology of Parkinson's disease and its sensitivity to milk consumption.