Tryptophan-enriched diet or 5-hydroxytryptophan supplementation given in a randomized controlled trial impacts social cognition on a neural and behavioral level.

Understanding of emotions and intentions are key processes in social cognition at which serotonin is an important neuromodulator. Its precursor is the essential amino acid tryptophan (TRP). Reduced TRP availability leads to weaker impulse control ability and higher aggression, while TRP supplementation promotes confidence. In a double-blind placebo-controlled fMRI study with 77 healthy adults, we investigated the influence of a 4 week TRP enriched diet and an acute 5-hydroxytryptophan (5-HTP) intake on two social-cognitive tasks, a moral evaluation and an emotion recognition task. With 5-HTP, immoral behavior without negative consequences was rated as more reprehensible. Additionally, during story reading, activation in insula and supramarginal gyrus was increased after TRP intake. No significant effects of TRP on emotion recognition were identified for the whole sample. Importantly, emotion recognition ability decreased with age which was for positive emotions compensated by TRP. Since the supramarginal gyrus is associated with empathy, pain and related information integration results could be interpreted as reflecting stricter evaluation of negative behavior due to better integration of information. Improved recognition of positive emotions with TRP in older participants supports the use of a TRP-rich diet to compensate for age related decline in social-cognitive processes.

Creatine Supplementation Upregulates mTORC1 Signaling and Markers of Synaptic Plasticity in the Dentate Gyrus While Ameliorating LPS-Induced Cognitive Impairment in Female Rats.

Mild cognitive impairment (MCI) designates the boundary area between cognitive function in natural aging and dementia, and this is viewed as a therapeutic window to prevent the occurrence of dementia. The current study investigated the neurocognitive effects of oral creatine (Cr) supplementation in young female Wistar rats that received intracerebroventricular injections of lipopolysaccharide (LPS) to mimic MCI. Neuromolecular changes within the dentate gyrus were analyzed following behavioral testing. We also investigated both neurocognitive and neuromolecular changes following Cr supplementation in the absence of LPS in young female Wistar rats to further investigate mechanisms. Interestingly, based on trial 2 of Barnes maze test, Cr supplementation ameliorated spatial learning and memory deficit induced by LPS, shown by decreased latency time and errors to reach the escape box (p < 0.0001, n = 12). Cr supplementation also attenuated recognition memory deficit induced by LPS, shown by increased amount of time taken to explore the new object (p = 0.002, n = 12) during novel object recognition testing. Within the dentate gyrus, Cr supplementation in LPS injected rats upregulated mTORC1 signaling (p = 0.026 for mTOR phosphorylation, p = 0.002 for p70S6K phosphorylation, n = 8) as well as the synapsin (p = 0.008) and PSD-95 synaptic proteins (p = 0.015), in comparisons to LPS injected rats. However, Cr supplementation failed to further enhance spatial memory and recognition memory in the absence of LPS. In conclusion, Cr ameliorates LPS-induced cognitive impairment in a rodent MCI model. Mechanistically, these phenotypic effects may, in part, be mitigated via an upregulation of mTORC1 signaling, and an enhancement in synaptogenesis in the dentate gyrus. While preliminary, these findings may inform future research investigating neurocognitive effects of Cr for MCI patients.

BDNF as a Putative Target for Standardized Extract of Ginkgo biloba-Induced Persistence of Object Recognition Memory.

Despite considerable progress on the study of the effect of standardized extract of Gingko biloba (EGb) on memory processes, our understanding of its role in the persistence of long-term memory (LTM) and the molecular mechanism underlying its effect, particularly episodic-like memory, is limited. We here investigated the effects of EGb on the long-term retention of recognition memory and its persistence and BDNF expression levels in the dorsal hippocampal formation (DHF). Adult male Wistar rats (n = 10/group) were handled for 10 min/5 day. On day 6, the animals were treated with vehicle or 0.4 mg/kg diazepam (control groups) or with EGb (250, 500 or 100 mg/kg) 30 min before the training session (TR1), in which the animals were exposed to two sample objects. On day 7, all rats underwent a second training session (TR2) as described in the TR1 but without drug treatment. Object recognition memory (ORM) was evaluated on day 8 (retention test, T1) and day 9 (persistence test, T2). At the end of T1or T2, animals were decapitated, and DHF samples were frozen at -80 °C for analyses of the differential expression of BDNF by Western blotting. EGb-treated groups spent more time exploring the novel object in T2 and showed the highest recognition index (RI) values during the T1 and T2, which was associated with upregulation of BDNF expression in the DHF in a dose-and session-dependent manner. Our data reveal, for the first time, that EGb treatment before acquisition of ORM promotes persistence of LTM by BDNF differential expression.

24(S)-Saringosterol Prevents Cognitive Decline in a Mouse Model for Alzheimer's Disease.

We recently found that dietary supplementation with the seaweed Sargassum fusiforme, containing the preferential LXRß-agonist 24(S)-saringosterol, prevented memory decline and reduced amyloid-ß (Aß) deposition in an Alzheimer's disease (AD) mouse model without inducing hepatic steatosis. Here, we examined the effects of 24(S)-saringosterol as a food additive on cognition and neuropathology in AD mice. Six-month-old male APPswePS1ΔE9 mice and wildtype C57BL/6J littermates received 24(S)-saringosterol (0.5 mg/25 g body weight/day) (APPswePS1ΔE9 n = 20; C57BL/6J n = 19) or vehicle (APPswePS1ΔE9 n = 17; C57BL/6J n = 19) for 10 weeks. Cognition was assessed using object recognition and object location tasks. Sterols were analyzed by gas chromatography/mass spectrometry, Aß and inflammatory markers by immunohistochemistry, and gene expression by quantitative real-time PCR. Hepatic lipids were quantified after Oil-Red-O staining. Administration of 24(S)-saringosterol prevented cognitive decline in APPswePS1ΔE9 mice without affecting the Aß plaque load. Moreover, 24(S)-saringosterol prevented the increase in the inflammatory marker Iba1 in the cortex of APPswePS1ΔE9 mice (p < 0.001). Furthermore, 24(S)-saringosterol did not affect the expression of lipid metabolism-related LXR-response genes in the hippocampus nor the hepatic neutral lipid content. Thus, administration of 24(S)-saringosterol prevented cognitive decline in APPswePS1ΔE9 mice independent of effects on Aß load and without adverse effects on liver fat content. The anti-inflammatory effects of 24(S)-saringosterol may contribute to the prevention of cognitive decline.

Study of Neuroprotection by a Combination of the Biological Antioxidant (Eucalyptus Extract) and the Antihypertensive Drug Candesartan against Chronic Cerebral Ischemia in Rats.

Chronic cerebral ischemia with a notable long-term cessation of blood supply to the brain tissues leads to sensorimotor defects and short- and long-term memory problems. Neuroprotective agents are used in an attempt to save ischemic neurons from necrosis and apoptosis, such as the antioxidant agent Eucalyptus. Numerous studies have demonstrated the involvement of the renin-angiotensin system in the initiation and progression of cardiovascular and neurodegenerative diseases. Candesartan is a drug that acts as an angiotensin II receptor 1 blocker. We established a rat model exhibiting sensorimotor and cognitive impairments due to chronic cerebral ischemia induced by the ligation of the right common carotid artery. Wistar male rats were randomly divided into five groups: Sham group, Untreated Ligated group, Ischemic group treated with Eucalyptus (500 mg/kg), Ischemic group treated with Candesartan (0.5 mg/kg), and Ischemic group treated with a combination of Eucalyptus and Candesartan. To evaluate the sensorimotor disorders, we performed the beam balance test, the beam walking test, and the modified sticky test. Moreover, the object recognition test and the Morris water maze test were performed to assess the memory disorders of the rats. The infarct rat brain regions were subsequently stained using the triphenyltetrazolium chloride staining technique. The rats in the Sham group had normal sensorimotor and cognitive functions without the appearance of microscopic ischemic brain lesions. In parallel, the untreated Ischemic group showed severe impaired neurological functions with the presence of considerable brain infarctions. The treatment of the Ischemic group with a combination of both Eucalyptus and Candesartan was more efficient in improving the sensorimotor and cognitive deficits (p < 0.001) than the treatment with Eucalyptus or Candesartan alone (p < 0.05), by the comparison to the non-treated Ischemic group. Our study shows that the combination of Eucalyptus and Candesartan could decrease ischemic brain injury and improve neurological outcomes.

Effects of the aqueous extract of Phyllanthus niruri Linn during pregnancy and lactation on neurobehavioral parameters of rats' offspring.

ETHNOPHARMACOLOGICAL RELEVANCE: Phyllanthus niruri L. (Phyllanthaceae) is a plant used in traditional medicine, mainly to treat kidney stones. However, the effects of maternal exposure to P. niruri remain poorly explored. AIM OF THE STUDY: The objective of this study was to investigate the effects of administration of aqueous extract of P. niruri (AEPN) during pregnancy and lactation, in maternal toxicity, reflex maturation, and offspring memory. MATERIALS AND METHODS: Pregnant rats were divided into three groups (n = 8/group): Control (vehicle), AEPN 75, and AEPN 150 (each respectively treated with P. niruri at a dose of 75 and 150 mg/kg/day). The animals were treated via intragastric gavage during pregnancy and lactation. Weight gain, feed intake, and reproductive performance were analyzed in the mothers. In the offspring, the following tests were performed: Neonatal Reflex Ontogeny, Open Field Habituation Test and the Object Recognition Test in adulthood. RESULTS: Maternal exposure to AEPN did not influence weight gain, feed intake, or reproductive parameters. In the offspring, anticipation of reflex ontogenesis (time of completion) was observed (p < 0.05). During adulthood, the AEPN groups presented decreases in exploratory activity upon their second exposure to the Open Field Habituation Test (in a dose-dependent manner) (p < 0.05). In the Object Recognition Test, administration of the extract at 75 and 150 mg/kg induced significant dose-dependent improvements in short and long-term memory (p < 0.05). CONCLUSION: Administration of the AEPN accelerated the reflex maturation in neonates, and improved offspring memory while inducing no maternal or neonatal toxicity.

Paeonol administration alleviates cognitive deficits and attenuates neural pathological changes in APP/PS1 mice.

Alzheimer's disease typically presents with impaired cognition and pathological morphologic changes, including the accumulation of amyloid-ß plaques. Disease-modifying drugs are in urgent need as neuroprotective therapies. Exploration of novel therapeutics for alleviating symptoms of Alzheimer's disease has found promise in plant extracts of functional phenols. Paeonol is a water-soluble phenolic substance that has been shown to confer diverse biological effects, including neuroprotection. An Alzheimer's disease model of APP/PS1 double transgenic mice was used in this study, and the therapeutic effects of paeonol were assessed after three weeks' administration. It was found that paeonol treatment significantly increased behavioral performance in the Morris water maze test and increased discrimination rate in the novel object recognition test compared to vehicle-treated APP/PS1 mice. Histologically, paeonol treatment significantly alleviated the Aß plaque burden, reduced neural loss, inhibited microglia activation, and decreased neuroinflammation in the brain of APP/PS1 mice. In addition, a number of Alzheimer's disease-related synaptic plasticity deficits were ameliorated. The present results indicate that paeonol significantly relieved amyloid-ß deposition and amyloid-ß -mediated neuropathology in the brain of APP/PS1 mice, suggesting the potential of paeonol as a preventive and therapeutic agent for Alzheimer's disease.

Orally Administered Cinnamon Extract Attenuates Cognitive and Neuronal Deficits Following Traumatic Brain Injury.

The present paper shows how cinnamon extract (CE) consumption mitigates neuronal loss and memory impairment following traumatic brain injury (TBI), one of the world's most common neurodegenerative diseases. TBI patients suffer short- and long-term behavioral, cognitive, and emotional impairments, including difficulties in concentration, memory loss, and depression. Research shows that CE application can mitigate cognitive and behavioral impairments in animal models for Alzheimer's and Parkinson's disease, whose pathophysiology is similar to that of TBI. This study builds on prior research by showing similar results in TBI mice models. After drinking CE for a week, mice were injured using our 70-g weight drop TBI device. For 2 weeks thereafter, the mice continued drinking CE alongside standard lab nutrition. Subsequently, the mice underwent behavioral tests to assess their memory, motor activity, and anxiety. The mice brains were harvested for immunohistochemistry staining to evaluate overall neuronal survival. Our results show that CE consumption almost completely mitigates memory impairment and decreases neuronal loss after TBI. Mice that did not consume CE demonstrated impaired memory. Our results also show that CE consumption attenuated neuronal loss in the temporal cortex and the dentate gyrus. Mice that did not consume CE suffered a significant neuronal loss. There were no significant differences in anxiety levels and motor activity between all groups. These findings show a new therapeutic approach to improve cognitive function and decrease memory loss after TBI.

N,N-dimethylglycine prevents toluene-induced impairment in recognition memory and synaptic plasticity in mice.

Toluene intoxication produces deleterious effects on cognitive function, which has been associated with the inhibition of N-methyl-d-aspartate receptor (NMDAR). The present study determined whether N,N-dimethylglycine (DMG), a nutrient supplement and a partial agonist for NMDAR glycine binding site, could counteract recognition memory deficits and hippocampal synaptic dysfunction after acute toluene exposure. Male ICR mice were treated with toluene (250-750 mg/kg) for monitoring the sociability and social novelty in three-chamber test and long-term potentiation (LTP) of hippocampal synaptic transmission. Moreover, the combined effects of DMG (30-100 mg/kg) pretreatment with toluene (750 mg/kg) on three-chamber test, novel location and object recognition test and synaptic function were determined. Toluene decreased the sociability, preference for social novelty, hippocampal synaptic transmission and LTP in a dose-dependent manner. DMG pretreatment significantly reduced the toluene-induced memory impairment in social recognition, object location and object recognition and synaptic dysfunction. Furthermore, NMDAR glycine binding site antagonist, 7-chlorokynurenic acid, abolished the protective effects of DMG. These results indicate that DMG could prevent toluene-induced recognition memory deficits and synaptic dysfunction and its beneficial effects might be associated with modulation of NMDAR. These findings suggest that DMG supplementation might be an effective approach to prevent memory problems for the workers at risk of high-level toluene exposure or toluene abusers.

Supplementation of Taurine Insulates Against Oxidative Stress, Confers Neuroprotection and Attenuates Memory Impairment in Noise Stress Exposed Male Wistar Rats.

Noise has always been an important environmental factor that induces health problems in the general population. Due to ever increasing noise pollution, humans are facing multiple auditory and non-auditory problems including neuropsychiatric disorders. In modern day life it is impossible to avoid noise due to the rapid industrialization of society. Continuous exposure to noise stress creates a disturbance in brain function which may lead to memory disorder. Therefore, it is necessary to find preventive measures to reduce the deleterious effects of noise exposure. Supplementation of taurine, a semi essential amino acid, is reported to alleviate psychiatric disorders. In this study noise-exposed (100 db; 3 h daily for 15 days) rats were supplemented with taurine at a dose of 100 mg/kg for 15 days. Spatial and recognition memory was assessed using the Morris water maze and novel object recognition task, respectively. Results of this study showed a reversal of noise-induced memory impairment in rats. The derangements of catecholaminergic and serotonergic levels in the hippocampus and altered brain antioxidant enzyme activity due to noise exposure were also restored by taurine administration. This study highlights the importance of taurine supplementation to mitigate noise-induced impaired memory via normalizing the neurochemical functions and reducing oxidative stress in rat brain.

Melatonin improves memory defects in a mouse model of multiple sclerosis by up-regulating cAMP-response element-binding protein and synapse-associated proteins in the prefrontal cortex.

Multiple sclerosis is a progressive autoimmune disorder of the myelin sheath and is the most common inflammatory disease of young adults. Up to 65% of multiple sclerosis patients have cognitive impairments such as memory loss and difficulty in understanding and maintaining attention and concentration. Many pharmacological interventions have been used to reverse motor impairments in multiple sclerosis patients; however, none of these drugs improve cognitive function. Melatonin can diffuse through the blood-brain barrier and has well-known antioxidant and anti-inflammatory properties with almost no side effects; it is, therefore, a promising neuroprotective supplement for many neurological diseases, such as multiple sclerosis, Alzheimer's disease, Parkinson's disease, ischemic stroke, and fibromyalgia. However, only some researches have assessed the effect of melatonin on cognitive dysfunction in multiple sclerosis. Here, we evaluated the effects of melatonin supplementation on memory defects induced by cuprizone in a mouse model of multiple sclerosis. Cuprizone (400 mg/kg) and melatonin (80 mg/kg) were administered to SWR/J mice daily for 5 weeks. Open field, tail-flick, and novel object recognition behavioral tests were performed. Also, expression of cAMP-response element-binding protein, synaptophysin, and postsynaptic density protein 95 were measured in the prefrontal cortex. Melatonin significantly improved the memory defects induced by cuprizone toxicity by up-regulating cAMP-response element-binding protein and by increasing expression of the synapse-associated synaptophysin and postsynaptic density protein 95 genes in the prefrontal cortex. These results indicate that melatonin may provide protective effects against memory impairments associated with multiple sclerosis.

Early-Life Supplementation of Bovine Milk Osteopontin Supports Neurodevelopment and Influences Exploratory Behavior.

INTRODUCTION: Osteopontin (OPN) is a whey protein found at high concentration in human milk and is involved in processes such as bone cell proliferation and differentiation. Milk OPN has shown to be involved in various aspects of development, including the immune system and gut health. However, the influence of dietary bovine milk OPN inclusion on brain and cognitive development has not been studied extensively until recently. This research examines whether dietary supplementation of bovine milk OPN supports brain and cognitive development in the translational pig model. METHODS: From postnatal day (PND) 2 to 34, twenty-one intact male pigs were provided ad libitum access to one of two dietary treatments, a standard soy protein isolate-based milk replacer to serve as a control diet (n = 11) and the same base diet supplemented with bovine milk OPN to serve as a test diet (n = 10). In addition to growth and health outcomes, recognition memory was tested using the novel object recognition (NOR) task from PND 28 to 32, and magnetic resonance imaging was conducted at PND 34 to evaluate brain development. RESULTS: No dietary effects were observed for growth performance or health indices. For the behavioral analysis, pigs that received the test diet exhibited shorter (p < 0.05) latency to the first object visited compared with pigs fed the control diet. Although the control group exhibited novelty preference, there was no difference in recognition index between dietary groups. Neuroimaging outcomes revealed increased (p < 0.05) relative brain volumes of the corpus callosum, lateral ventricle, left and right internal capsule, left and right putamen-globus pallidus, and right hippocampus, and right cortex in the test group. Diffusion tensor imaging revealed higher (p < 0.05) radial diffusivity in the corpus callosum and lower (p < 0.05) fractional anisotropy in pigs provided the test diet. CONCLUSION: Dietary supplementation of bovine milk OPN increased the relative volume of several brain regions and altered behaviors in the NOR task. Underlying mechanisms of bovine milk OPN influencing the development of brain structures and additional behaviors warrant further investigation.

Casticin ameliorates scopolamine-induced cognitive dysfunction in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: The fruit of Vitex rotundifolia L. (Verbenaceae) has been used in traditional medicine as sedative or analgesic agent for headache. Recent population-based cohort studies have shown that headache including migraines is a risk factor for dementia. Thus, the fruit of V. rotundifolia may be useful for treating cognitive dysfunction observed in dementia. AIM OF THE STUDY: We had previously found that the ethanolic extract of the fruit of V. rotundifolia ameliorated cognitive dysfunction and isolated casticin as an active compound. In the present study, we studied the effect of casticin on a mouse model of cognitive impairment induced by scopolamine. MATERIALS AND METHODS: Mice were treated with the ethanolic extract of the fruit of V. rotundifolia (EEVR; 30, 100 or 300 mg/kg, p.o.) or casticin (0.3, 1 or 3 mg/kg, p.o.). We examined the effect of casticin or EEVR using the passive avoidance test, the Morris water maze test and the novel object recognition test. Scopolamine (1 mg/kg, i.p.) was used to induce cognitive impairment by blocking cholinergic neurotransmitter system. We investigated the effects of casticin on acetylcholinesterase (AchE) activity and the phosphorylation levels of extracellular signal-regulated kinase (ERK), cAMP response element binding protein (CREB), and the expression levels of brain-derived neurotrophic factor (BDNF). RESULTS: EEVR (100 and 300 mg/kg, p.o.) significantly ameliorated the latency in the passive avoidance test, and casticin (1 and 3 mg/kg, p.o.) also significantly improved the latency in the passive avoidance test, novel object preference in the novel object recognition test, and swimming time in the target quadrant of the Morris water maze test. Casticin also decreased AChE activity in ex vivo analysis and increased the phosphorylation levels of memory-related signaling molecules, such as ERK, CREB and BDNF in the cortex. CONCLUSION: These results suggest that casticin ameliorates cholinergic blockade-induced cognitive impairment, in part, through the inhibition of AChE and the activation of the ERK-CREB-BDNF signaling pathway. Taken together, the results suggest that casticin may be useful for treating the cognitive dysfunction observed during cholinergic impairment.

Tea polyphenols protect learning and memory in sleep-deprived mice by promoting AMPA receptor internalization.

Chronic sleep loss caused lots of health problems, also including cognition impairment. Tea is one of the most popular drinks when people stay up late. Nevertheless, the effects of tea on sleep deprivation-induced cognition impairment are still unclear. In the present study, we found 24-h sleep deprivation (S-DEP) increased membrane α-amino-3-hydroxy-5-methyl-4-isoxa-zolep-propionate (AMPA) receptor level through a tumor necrosis factor α (TNFα)-dependent pathway in hippocampi. Blocking elevated TNFα level can protect S-DEP mice from impaired learning ability according to behavioral test. Tea polyphenols, major active compounds in green tea, suppressed TNFα production through downregulating TNFα converting enzyme (TACE) level. Meanwhile, tea polyphenols treatment could ameliorate recognition impairment and anxiety-like behaviors in S-DEP mice. The aforementioned results demonstrate cognition protective effects of tea polyphenols in S-DEP mice model, which provide a theoretical basis for the treatments of S-DEP-induced cognition impairment by targeting the TACE/TNFα/AMPA pathway.

Supplemental taurine during adolescence and early adulthood has sex-specific effects on cognition, behavior and neurotransmitter levels in C57BL/6J mice dependent on exposure window.

The mammalian brain goes through final maturation during late adolescence and early adulthood with sex differences in timing. The key cellular processes, including changes in neurotransmitter receptor density and synaptic pruning, make this age uniquely vulnerable to neurotoxic insults. Teenagers and young adults are the major consumers of energy drinks, which contain high levels of taurine and caffeine. Taurine is one of the most abundant amino acids in the central nervous system, but the effects of supplemental taurine consumption during adolescence has not been well studied. We conducted an initial short-term exposure study with 0.12% taurine in drinking water and a long-term exposure dose-response study using 0.06 and 0.12% taurine in male and female C57BL/6J mice. We examined a broad range of cognitive functions and behaviors and measured neurotransmitter levels. We found no significant differences in anxiety, open field locomotor activity, or sensorimotor gating. However, we found impairments in novel object recognition and sex differences in Morris water maze. When taurine treatment stopped before behavioral experiments began, male mice had significant impairments in spatial learning and memory. In the dose-response study when taurine treatment continued throughout behavioral experiments, females had significant impairments. We also found sex differences in neurotransmitter levels with females having higher levels of glutamate, DOPAC and 5-HIAA. We conclude that both females and males are at risk from excess taurine consumption during final brain maturation.

A botanical drug composed of three herbal materials attenuates the sensorimotor gating deficit and cognitive impairment induced by MK-801 in mice.

OBJECTIVES: A botanical drug derived from the ethanolic extract composed of Clematis chinensis Osbeck (Ranunculaceae), Trichosanthes kirilowii Maximowicz (Cucurbitaceae) and Prunella vulgaris Linné (Lamiaceae) has been used to ameliorate rheumatoid arthritis as an ethical drug in Korea. In our study, we investigated the effect of this herbal complex extract (HCE) on schizophrenia-like behaviours induced by MK-801. METHODS: HCE (30, 100 or 300 mg/kg, p.o) was orally administered to male ICR mice to a schizophrenia-like animal model induced by MK-801. We conducted an acoustic startle response task, an open-field task, a novel object recognition task and a social novelty preference task. KEY FINDINGS: We found that a single administration of HCE (100 or 300 mg/kg) ameliorated MK-801-induced abnormal behaviours including sensorimotor gating deficits and social or object recognition memory deficits. In addition, MK-801-induced increases in phosphorylated Akt and GSK-3ß expression levels in the prefrontal cortex were reversed by HCE (30, 100 or 300 mg/kg). CONCLUSIONS: These results imply that HCE ameliorates MK-801-induced dysfunctions in prepulse inhibition, social interactions and cognitive function, partly by regulating the Akt and GSK-3ß signalling pathways.

Effects of transcranial photobiomodulation and methylene blue on biochemical and behavioral profiles in mice stress model.

The effectiveness of transcranial photobiomodulation (tPBM) and methylene Blue (MB) in treating learning and memory impairments is previously reported. In this study, we investigated the effect of tPBM and MB in combination or alone on unpredictable chronic mild stress (UCMS)-induced learning and memory impairments in mice. Fifty-five male BALB/c mice were randomly allocated to five groups: control, laser sham + normal saline (NS), tPBM + NS, laser sham + MB, and tPBM + MB. All groups except the control underwent UCMS and were treated simultaneously for 4 weeks. Elevated plus maze (EPM) was used to evaluate anxiety-like behaviors. Novel object recognition (NOR) test and Barnes maze tests were used to evaluate learning and memory function. The serum cortisol and brain nitric oxide (NO), reactive oxygen species (ROS), total antioxidant capacity (TAC), glutathione peroxidase (GPx), and superoxide dismutase (SOD) levels were measured by spectrophotometric methods. Behavioral tests revealed that UCMS impaired learning and memory, and treatment with PBM, MB, and their combination reversed these impairments. Levels of NO, ROS, SOD activity in brain, and serum cortisol levels significantly increased while brain GPx activity and total antioxidant capacity significantly decreased in the sham + NS animals when compared with the controls. A significant improvement was observed in treatment groups due to reversion of the aforementioned molecular analysis caused by UCMS when it was compared with control levels. Both tPBM and MB in combination or alone have significant therapeutic effects on learning and memory impairments in UCMS-received animals.

Vitamin D3 favorable outcome on recognition memory and prefrontal cortex expression of choline acetyltransferase and acetylcholinesterase in experimental model of chronic high-fat feeding.

Aim of the study: High-fat diet (HFD) consumption and insufficient vitamin D levels are globally increasing phenomena. The present study assessed the effect of chronic HFD feeding with and without vitamin D supplementation on recognition memory and prefrontal cortex expression of choline acetyltransferase (CAT) and acetylcholinesterase (Achase).Materials and methods: Forty male Wistar rats were subjected to four dietary regimens (n = 10); control diet (10% fat), control + vitamin D3, high-fat diet (HFD 45% fat) and HFD + vitamin D3 for 6 months. Rats were tested for the novel object recognition test, and their prefrontal cortices were assessed for expression of CAT and Achase.Results: Recognition memory was impaired in HFD-fed rats compared to control rats as evidenced by significantly decreased discrimination index in the novel object recognition test. Moreover, CAT expression was significantly decreased while Achase expression was significantly increased in the prefrontal cortex of HFD-fed rats. Vitamin D3 supplementation with HFD significantly increased the exploration of the novel object and the discrimination index and attenuated the alterations in the prefrontal cortex CAT and Achase expression.Conclusions: The present findings support the potential effect of vitamin D on recognition memory and cholinergic transmission in the prefrontal cortex and add to the pathophysiology of HFD consumption.

Behavior, protein, and dendritic changes after model traumatic brain injury and treatment with nanocoffee particles.

BACKGROUND: Traumatic brain injury (TBI) is a widespread public health problem and a signature injury of our military in modern conflicts. Despite the long-term effects of even mild brain injuries, an effective treatment remains elusive. Coffee and several of its compounds, including caffeine, have been identified as having neuroprotective effects in studies of neurodegenerative disease. Given the molecular similarities between TBI and neurodegenerative disease, we have devised a study to test a nanocoffee extract in the treatment of a mouse model of mild TBI. RESULTS: After a single injury and two subsequent injections of nanocoffee, we identified treatment as being associated with improved behavioral outcomes, favorable molecular signaling changes, and dendritic changes suggestive of improved neuronal health. CONCLUSIONS: We have identified coffee extracts as a potential viable multifaceted treatment approach to target the secondary injury associated with TBI.

Natural hypothalamic circuit dynamics underlying object memorization.

Brain signals that govern memory formation remain incompletely identified. The hypothalamus is implicated in memory disorders, but how its rapidly changing activity shapes memorization is unknown. During encounters with objects, hypothalamic melanin-concentrating hormone (MCH) neurons emit brief signals that reflect object novelty. Here we show that targeted optogenetic silencing of these signals, performed selectively during the initial object encounters (i.e. memory acquisition), prevents future recognition of the objects. We identify an upstream inhibitory microcircuit from hypothalamic GAD65 neurons to MCH neurons, which constrains the memory-promoting MCH cell bursts. Finally, we demonstrate that silencing the GAD65 cells during object memory acquisition improves future object recognition through MCH-receptor-dependent pathways. These results provide causal evidence that object-associated signals in genetically distinct but interconnected hypothalamic neurons differentially control whether the brain forms object memories. This gating of memory formation by hypothalamic activity establishes appropriate behavioral responses to novel and familiar objects.