Impaired Motor Coordination Research Articles

Long-Term Soft-Food Rearing in Young Mice Alters Brain Function and Mood-Related Behavior.

The relationship between caloric and nutrient intake and overall health has been extensively studied. However, little research has focused on the impact of the hardness of staple foods on health. In this study, we investigated the effects of a soft diet on brain function and behavior in mice from an early age. Mice fed a soft diet for six months exhibited increased body weight and total cholesterol levels, along with impaired cognitive and motor function, heightened nocturnal activity, and increased aggression. Interestingly, when these mice were switched back to a solid diet for three months, their weight gain ceased, total cholesterol levels stabilized, cognitive function improved, and aggression decreased, while their nocturnal activity remained high. These findings suggest that long-term consumption of a soft diet during early development can influence various behaviors associated with anxiety and mood regulation, including weight gain, cognitive decline, impaired motor coordination, increased nocturnal activity, and heightened aggression. Therefore, the hardness of food can impact brain function, mental well-being, and motor skills during the developmental stage. Early consumption of hard foods may be crucial for promoting and maintaining healthy brain function.

Rosuvastatin Synergistically Enhances the Antinociceptive Efficacy of Duloxetine in Paclitaxel-Induced Neuropathic Pain in Mice.

Paclitaxel, a widely used cancer chemotherapeutic agent, has high incidence of neurotoxicity associated with the production of neuropathic pain, for which only duloxetine has shown significant but moderate analgesic effect. Since statins, classically used to reduce hypercholesterolemia, have shown antinociceptive effect in preclinical studies on neuropathic pain, we studied whether the antinociceptive efficacy of duloxetine could be synergistically potentiated by rosuvastatin in a model of paclitaxel-induced neuropathy in mice. The astrocytic and microglial responses in the spinal cord of paclitaxel-treated mice were also assessed by measuring GFAP and CD11b proteins, respectively. Paclitaxel treatment did not impair motor coordination and balance in rotarod testing. Rosuvastatin, duloxetine, and the rosuvastatin/duloxetine combination (combined at equieffective doses) dose-dependently decreased mechanical allodynia (ED30, von Frey testing) and thermal hyperalgesia (ED50, hot plate testing) in paclitaxel-treated mice. Isobolographic analysis showed a superadditive interaction for rosuvastatin and duloxetine, as both the ED30 and ED50 for the rosuvastatin/duloxetine combination contained only a quarter of each drug compared to the individual drugs. The rosuvastatin/duloxetine combination reversed paclitaxel-induced GFAP overexpression, indicating that such effects might depend in part on astrocyte inactivation. Results suggest that statins could be useful in synergistically enhancing the efficacy of duloxetine in some chemotherapy-induced neuropathic conditions.

Repeated donkey milk consumption reduces anxiety-like behaviors and brain oxidative damage to lipids in mice

Donkey milk (DM) is a source of bioactive compounds that can benefit neural functioning. In the present study, we investigated the effects of DM consumption on anxiolytic-related, despair-like, locomotion and coordination behaviors, as well as the provision of protection from oxidative damage to lipids and proteins in brain tissues and melatonin plasma levels. To achieve this, male mice orally received DM (4 g.kg-1) or vehicle for 18 days. Their behavior was assessed in the following tests: elevated plus maze (EPM), open field and rotarod tests (OF, RR) and forced swimming test (FST). Acute treatments with diazepam (DZP, 1.5 mg.kg-1, v.o.), fluoxetine (FLX, 20 mg.kg-1, i.p.) and nortriptyline (NTP, 20 mg.kg-1, i.p.) were used as positive controls. On the eighteenth day, the animals were euthanized and brain tissue and blood were collected to measure oxidative damage, and melatonin plasma levels. Similar to DZP, repeated DM consumption reduced exploration to open areas in the EPM test. Under our experimental conditions, conventional antidepressants reduced immobility time in the FST, and the benzodiazepine treatment impaired motor coordination in mice. No significant differences in locomotion, motor coordination and despair-related behaviors were observed in the mice treated with DM when assessed in the EPM, OF, RR and FST, respectively. Biochemical assays showed that repeated DM exposition protected against oxidative damage to lipids and increased plasma levels of melatonin. These findings suggest consumption of DM may be a promising food for the treatment of anxiety-related disorders, without depressant effects on the central nervous system.

Reasons for use and experiences of using phenibut, a mixed methods analysis of online reports

ABSTRACT Background: Phenibut is a drug similar in structure to gabapentin and pregabalin. It is available online without prescription, often marketed as a dietary supplement or amino acid derivative. Little is known about phenibut use despite its increased popularity in the United States over the last decade. Objective: To clarify reasons for taking phenibut, circumstances, and effects of use. Methods: Reports of phenibut, gabapentin, and pregabalin use were downloaded from a publicly-available database, Erowid.org. A mixed methods approach utilizing qualitative content analysis was used. Results: Of 229 reports, 211 were from male authors. People usually purchased phenibut online and reportedly used it for recreation, to manage a medical or psychiatric problem (primarily insomnia, anxiety), as a substitute for other drugs (especially benzodiazepines), to manage withdrawal from another substance (including benzodiazepines, opioids), and/or for performance enhancement. While it shared many reported effects with pregabalin and gabapentin such as anxiolysis, increased talkativeness, and impaired motor coordination, reports of gastrointestinal distress and sedation were more commonly attributed to phenibut. Several people reported difficulty in restricting their use and managing withdrawal. Conclusions: Phenibut reports suggest that phenibut may have some benefits for some people. Use also, however, carries risks of adverse effects, a potentially dangerous withdrawal syndrome, and addiction. Not dissimilar to unprescribed gabapentin or pregabalin, self-medication is a common motive for phenibut use. Physicians should continue to ask their patients about use of any non-prescribed medications, dietary supplements, or “amino acid derivatives.”Abbreviation: PWUPh: people who use phenibut; PWUG: people who use gabapentin; PWUPr: people who use pregabalin

Alteration in mitochondrial dynamics promotes the proinflammatory response of microglia and is involved in cerebellar dysfunction of young and aged mice following LPS exposure

Cerebellar dysfunction is implicated in impaired motor coordination and balance, thus disturbing the dynamics of sensorimotor integration. Neuroinflammation and aging could be prominent contributors to cerebellar aberration. Additionally, changes in mitochondrial dynamics may precede microglia activation in several chronic neurodegenerative diseases; however, the underlying mechanism remains largely unknown. Here using LPS (1 mg/kg i.p. for four consecutive days) stimulation in both young (3 months old) and aged (12 months old) mice, followed by molecular analysis on the 21st day, we have explored the correlation between aging and mitochondrial dynamic alteration in the backdrop of chronic neuroinflammation. Following LPS stimulation, we observed microglia activation and subsequent elevation in proinflammatory cytokines (M1; TNF-α, IFN-γ) with NLRP3 activation and a concomitant reduction in the expression of anti-inflammatory markers (M2; YM1, TGF-β1) in the cerebellar tissue of aged mice compared with the young LPS and aged controls. Remarkably, senescence (p21, p27, p53) and epigenetic (HDAC2) markers were found upregulated in the cerebellum tissue of the aged LPS group, suggesting their crucial role in LPS-induced cerebellar deficit. Further, we demonstrated alteration in the antagonistic forces of mitochondrial fusion and fission with increased expression of the mitochondrial fission-related gene [FIS1] and decreased fusion-related genes [MFN1 and MFN2]. We noted increased mtDNA copy number, microglia activation, and inflammatory response of IL1-β and IFN-γ post-chronic neuroinflammation in aged LPS group. Our results suggest that the crosstalk between mitochondrial dynamics and altered microglial activation paradigm in chronic neuroinflammatory conditions may be the key to understanding the cerebellar molecular mechanism.

Preclinical data on morpholine (3,5-di-tertbutyl-4-hydroxyphenyl) methanone induced anxiolysis.

Trimetozine is used to be indicated for the treatment of mental illnesses, particularly anxiety. The present study provides data on the pharmacological profile of trimetozine derivative morpholine (3,5-di-tert-butyl-4-hydroxyphenyl) methanone (LQFM289) which was designed from molecular hybridization of trimetozine lead compound and 2,6-di-tert-butyl-hydroxytoluene to develop new anxiolytic drugs. Here, we conduct molecular dynamics simulations, docking studies, receptor binding assays, andin silicoADMET profiling of LQFM289 before its behavioral and biochemical assessment in mice within the dose range of 5-20mg/kg. The docking of LQFM289 showed strong interactions with the benzodiazepine binding sites and matched well with receptor binding data. With the ADMET profile of this trimetozine derivative that predicts a high intestinal absorption and permeability to blood-brain barrier without being inhibited by the permeability glycoprotein, the oral administration of LQFM289 10mg/kg consistently induced anxiolytic-like behavior of the mice exposed to the open field and light-dark box apparatus without eliciting motor incoordination in the wire, rotarod, and chimney tests. A decrease in the wire and rotarod´s fall latency coupled with an increase in the chimney test´s climbing time and a decrease in the number of crossings in the open field apparatus at the dose of 20mg/kg of this trimetozine derivative suggest sedative or motor coordination impairment at this highest dose. The attenuation of the anxiolytic-like effects of LQFM289 (10mg/kg) by flumazenil pretreatment implicates the participation of benzodiazepine binding sites. The lowering of corticosterone and tumor necrosis factor alpha (cytokine) in LQFM289-treated mice at a single oral (acute) dose of 10mg/kg suggests that the anxiolytic-like effect of this compound also involves the recruitment of non-benzodiazepine binding sites/GABAergic molecular machinery.

Degeneration of muscle spindles in a murine model of Pompe disease

Pompe disease is a debilitating medical condition caused by a functional deficiency of lysosomal acid alpha-glucosidase (GAA). In addition to muscle weakness, people living with Pompe disease experience motor coordination deficits including an instable gait and posture. We reasoned that an impaired muscle spindle function might contribute to these deficiencies and therefore analyzed proprioception as well as muscle spindle structure and function in 4- and 8-month-old Gaa−/− mice. Gait analyses showed a reduced inter-limb and inter-paw coordination in Gaa−/− mice. Electrophysiological analyses of single-unit muscle spindle proprioceptive afferents revealed an impaired sensitivity of the dynamic and static component of the stretch response. Finally, a progressive degeneration of the sensory neuron and of the intrafusal fibers was detectable in Gaa−/− mice. We observed an increased abundance and size of lysosomes, a fragmentation of the inner and outer connective tissue capsule and a buildup of autophagic vacuoles in muscle spindles from 8-month-old Gaa−/− mice, indicating lysosomal defects and an impaired autophagocytosis. These results demonstrate a structural and functional degeneration of muscle spindles and an altered motor coordination in Gaa−/− mice. Similar changes could contribute to the impaired motor coordination in patients living with Pompe disease.

Hyperbaric Oxygen Therapy Attenuated the Motor Coordination and Cognitive Impairment of Polyglutamine Spinocerebellar Ataxia SCA17 Mice

Spinocerebellar ataxias (SCAs) are a large and diverse group of autosomal-dominant neurodegenerative diseases. No drugs have been approved for these relentlessly progressive and fatal SCAs. Our previous studies indicate that oxidative stress, neuroinflammation, and neuronal apoptosis are elevated in the SCA17 mice, which are the main therapeutic targets of hyperbaric oxygen treatment (HBOT). HBOT is considered to be an alternative and less invasive therapy for SCAs. In this study, we evaluated the HBOT (2.2 ATA for 14 days) effect and the persistence for the management of SCA17 mice and their wild-type littermates. We found HBOT attenuated the motor coordination and cognitive impairment of SCA17 mice and which persisted for about 1 month after the treatment. The results of several biochemistry and liver/kidney hematoxylin and eosin staining show the HBOT condition has no obvious toxicity in the mice. Immunostaining analyses show that the neuroprotective effect of HBOT could be through the promotion of BDNF production and the amelioration of neuroinflammation. Surprisingly, HBOT executes different effects on the male and female SCA17 mice, including the reduction of neuroinflammation and activation of CaMKII and ERK. This study suggests HBOT is a potential alternative therapeutic treatment for SCA17. Accumulated findings have revealed the similarity in disease pathomechanisms and possible therapeutic strategies in polyQ diseases; therefore, HBOT could be an optional treatment as well as the other polyQ diseases.

BALB.NCT-Cpoxnct is a unique mouse model of hereditary coproporphyria

In humans, mutations in the coproporphyrinogen oxidase (CPOX) gene can result in hereditary coproporphyria (HCP), characterized by high levels of coproporphyrin excretion in the urine and feces, as well as acute neurovisceral and chronic cutaneous manifestations. Appropriate animal models for comprehending the precise pathogenesis mechanism of HCP have not been reported that show similarities in terms of gene mutation, reduced CPOX activity, excess coproporphyrin accumulation, and clinical symptoms. As previously discovered, the BALB.NCT-Cpoxnct mouse carries a hypomorphic mutation in the Cpox gene. Due to the mutation, BALB.NCT-Cpoxnct had a drastic increase in coproporphyrin in the blood and liver persistently from a young age. In this study, we found that BALB.NCT-Cpoxnct mice manifested HCP symptoms. Similar to HCP patients, BALB.NCT-Cpoxnct excreted an excessive amount of coproporphyrin and porphyrin precursors in the urine and displayed neuromuscular symptoms, such as a lack of grip strength and impaired motor coordination. Male BALB.NCT-Cpoxnct had nonalcoholic steatohepatitis (NASH)-like liver pathology and sclerodermatous skin pathology. A portion of male mice had liver tumors as well, whereas female BALB.NCT-Cpoxnct lacked these hepatic and cutaneous pathologies. In addition, we discovered that BALB.NCT-Cpoxnct exhibited microcytic anemia. These results indicate that BALB.NCT-Cpoxnct mice serve as the suitable animal model to help gain insight into the pathogenesis and therapy of HCP.

Deficiency of Perry syndrome-associated p150Glued in midbrain dopaminergic neurons leads to progressive neurodegeneration and endoplasmic reticulum abnormalities

Multiple missense mutations in p150Glued are linked to Perry syndrome (PS), a rare neurodegenerative disease pathologically characterized by loss of nigral dopaminergic (DAergic) neurons. Here we generated p150Glued conditional knockout (cKO) mice by deleting p150Glued in midbrain DAergic neurons. The young cKO mice displayed impaired motor coordination, dystrophic DAergic dendrites, swollen axon terminals, reduced striatal dopamine transporter (DAT), and dysregulated dopamine transmission. The aged cKO mice showed loss of DAergic neurons and axons, somatic accumulation of α-synuclein, and astrogliosis. Further mechanistic studies revealed that p150Glued deficiency in DAergic neurons led to the reorganization of endoplasmic reticulum (ER) in dystrophic dendrites, upregulation of ER tubule-shaping protein reticulon 3, accumulation of DAT in reorganized ERs, dysfunction of COPII-mediated ER export, activation of unfolded protein response, and exacerbation of ER stress-induced cell death. Our findings demonstrate the importance of p150Glued in controlling the structure and function of ER, which is critical for the survival and function of midbrain DAergic neurons in PS.

Novel, thalidomide-like, non-cereblon binding drug tetrafluorobornylphthalimide mitigates inflammation and brain injury

BackgroundQuelling microglial-induced excessive neuroinflammation is a potential treatment strategy across neurological disorders, including traumatic brain injury (TBI), and can be achieved by thalidomide-like drugs albeit this approved drug class is compromised by potential teratogenicity. Tetrafluorobornylphthalimide (TFBP) and tetrafluoronorbornylphthalimide (TFNBP) were generated to retain the core phthalimide structure of thalidomide immunomodulatory imide drug (IMiD) class. However, the classical glutarimide ring was replaced by a bridged ring structure. TFBP/TFNBP were hence designed to retain beneficial anti-inflammatory properties of IMiDs but, importantly, hinder cereblon binding that underlies the adverse action of thalidomide-like drugs.MethodsTFBP/TFNBP were synthesized and evaluated for cereblon binding and anti-inflammatory actions in human and rodent cell cultures. Teratogenic potential was assessed in chicken embryos, and in vivo anti-inflammatory actions in rodents challenged with either lipopolysaccharide (LPS) or controlled cortical impact (CCI) moderate traumatic brain injury (TBI). Molecular modeling was performed to provide insight into drug/cereblon binding interactions.ResultsTFBP/TFNBP reduced markers of inflammation in mouse macrophage-like RAW264.7 cell cultures and in rodents challenged with LPS, lowering proinflammatory cytokines. Binding studies demonstrated minimal interaction with cereblon, with no resulting degradation of teratogenicity-associated transcription factor SALL4 or of teratogenicity in chicken embryo assays. To evaluate the biological relevance of its anti-inflammatory actions, two doses of TFBP were administered to mice at 1 and 24 h post-injury following CCI TBI. Compared to vehicle treatment, TFBP reduced TBI lesion size together with TBI-induction of an activated microglial phenotype, as evaluated by immunohistochemistry 2-weeks post-injury. Behavioral evaluations at 1- and 2-weeks post-injury demonstrated TFBP provided more rapid recovery of TBI-induced motor coordination and balance impairments, versus vehicle treated mice.ConclusionTFBP and TFNBP represent a new class of thalidomide-like IMiDs that lower proinflammatory cytokine generation but lack binding to cereblon, the main teratogenicity-associated mechanism. This aspect makes TFBP and TFNBP potentially safer than classic IMiDs for clinical use. TFBP provides a strategy to mitigate excessive neuroinflammation associated with moderate severity TBI to, thereby, improve behavioral outcome measures and warrants further investigation in neurological disorders involving a neuroinflammatory component.Graphical

Clinical Impact of the CYP2C19 Gene on Diazepam for the Management of Alcohol Withdrawal Syndrome.

Diazepam is a benzodiazepine widely prescribed for the management of patients with severe alcohol withdrawal syndrome to prevent agitation, withdrawal seizures, and delirium tremens. Despite standard dosing of diazepam, a subset of patients experience refractory withdrawal syndromes or adverse drug reactions, such as impaired motor coordination, dizziness, and slurred speech. The CYP2C19 and CYP3A4 enzymes play a key role in the biotransformation of diazepam. Given the highly polymorphic nature of the CYP2C19 gene, we reviewed the clinical impact of variants in the CYP2C19 gene on both the pharmacokinetics of diazepam and treatment outcomes related to the management of alcohol withdrawal syndrome.

Neuroprotective and Immunomodulatory Effects of Probiotics in a Rat Model of Parkinson's Disease.

It is now well recognized that a bidirectional relationship between gut microbiota and the brain, referred to as the gut-brain axis, plays a prominent role in maintaining homeostasis and that a disruption in this axis can result in neuroinflammatory response and neurological disorders such as Parkinson's disease (PD). The protective action of probiotics such as Bifidobacterium animalis ssp. lactis Bb12 and Lactobacillus rhamnosus GG in various animal models of PD has been reported. Therefore, in this study, we used an inflammatory model of PD to assess the effects of a combination of these two probiotics (Microbiot®) on motor behavior as well as on the response of microglia, including microglia morphology, to gain a better understanding of their mechanism of action. Microbiot® (300 µL) was administered orally once daily for 15days in a lipopolysaccharide-induced PD model using male Wistar rats. Although LPS-induced motor asymmetry in cylinder test was not affected by Microbiot®, impairment of motor coordination in the narrow-beam test was significantly reduced by this probiotic. Moreover, Microbiot® treatment reduced microglial activation suggesting an anti-inflammatory effect. While further mechanistic investigation of Microbiot® in neurodegenerative diseases is warranted, our results support the potential utility of probiotics in PD.

α7 nicotinic acetylcholine receptor agonist improved brain injury and impaired glucose metabolism in a rat model of ischemic stroke.

Vagus nerve stimulation through the action of acetylcholine can modulate inflammatory responses and metabolism. α7 Nicotinic Acetylcholine Receptor (α7nAChR) is a key component in the biological functions of acetylcholine. To further explore the health benefits of vagus nerve stimulation, this study aimed to investigate whether α7nAChR agonists offer beneficial effects against poststroke inflammatory and metabolic changes and to identify the underlying mechanisms in a rat model of stroke established by permanent cerebral ischemia. We found evidence showing that pretreatment with α7nAChR agonist, GTS-21, improved poststroke brain infarction size, impaired motor coordination, brain apoptotic caspase 3 activation, dysregulated glucose metabolism, and glutathione reduction. In ischemic cortical tissues and gastrocnemius muscles with GTS-21 pretreatment, macrophages/microglia M1 polarization-associated Tumor Necrosis Factor-α (TNF-α) mRNA, Cluster of Differentiation 68 (CD68) protein, and Inducible Nitric Oxide Synthase (iNOS) protein expression were reduced, while expression of anti-inflammatory cytokine IL-4 mRNA, and levels of M2 polarization-associated CD163 mRNA and protein were increased. In the gastrocnemius muscles, stroke rats showed a reduction in both glutathione content and Akt Serine 473 phosphorylation, as well as an elevation in Insulin Receptor Substrate-1 Serine 307 phosphorylation and Dynamin-Related Protein 1 Serine 616 phosphorylation. GTS-21 reversed poststroke changes in the gastrocnemius muscles. Overall, our findings, provide further evidence supporting the neuroprotective benefits of α7nAChR agonists, and indicate that they may potentially exert anti-inflammatory and metabolic effects peripherally in the skeletal muscle in an acute ischemic stroke animal model.

Microglial depletion exacerbates motor impairment and dopaminergic neuron loss in a 6-OHDA model of Parkinson's disease

6-hydroxydopamine (6-OHDA) is a common neurotoxin used to induce Parkinson's disease (PD) in mice, exerting neurotoxic effects through the production of reactive oxygen species and microglial activation. However, the role of microglia in PD is still not clear, with contradictory reports showing neuroprotection or exacerbation of neuronal death. Microglial depletion aggravates motor coordination impairments and reduces tyrosine hydroxylase positive neurons in the substantia nigra pars compacta. Moreover, MeCP2 and Adora1 genes expression were downregulated, suggesting they may be involved in the neurodegenerative process. This study highlights that microglia plays a protective role in dopaminergic neuron survival during the initial phase of PD, and the investigation of the mechanisms of this effect in future studies will help elucidate the pathophysiology of PD.

A fatal alliance: Glial connexins, myelin pathology and mental disorders

Mature oligodendrocytes are myelin forming glial cells which are responsible for myelination of neuronal axons in the white matter of the central nervous system. Myelin pathology is a major feature of severe neurological disorders. Oligodendrocyte-specific gene mutations and/or white matter alterations have also been addressed in a variety of mental disorders. Breakdown of myelin integrity and demyelination is associated with severe symptoms, including impairments in motor coordination, breathing, dysarthria, perception (vision and hearing), and cognition. Furthermore, there is evidence indicating that myelin sheath defects and white matter pathology contributes to the affective and cognitive symptoms of patients with mental disorders. Oligodendrocytes express the connexins GJC2; mCx47 [human (GJC2) and mouse (mCx47) connexin gene nomenclature according to Söhl and Willecke (2003)], GJB1; mCx32, and GJD1; mCx29 in both white and gray matter. Preclinical findings indicate that alterations in connexin expression in oligodendrocytes and astrocytes can induce myelin defects. GJC2; mCx47 is expressed at early embryonic stages in oligodendrocyte precursors cells which precedes central nervous system myelination. In adult humans and animals GJC2, respectively mCx47 expression is essential for oligodendrocyte function and ensures adequate myelination as well as myelin maintenance in the central nervous system. In the past decade, evidence has accumulated suggesting that mental disorders can be accompanied by changes in connexin expression, myelin sheath defects and corresponding white matter alterations. This dual pathology could compromise inter-neuronal information transfer, processing and communication and eventually contribute to behavioral, sensory-motor, affective and cognitive symptoms in patients with mental disorders. The induction of myelin repair and remyelination in the central nervous system of patients with mental disorders could help to restore normal neuronal information propagation and ameliorate behavioral and cognitive symptoms in individuals with mental disorders.

14-3-3γ haploinsufficiency leads to altered dopamine pathway and Parkinson’s disease-like motor incoordination in mice

The 14-3-3 protein family with seven isoforms found in mammals is widely expressed in the brain and plays various roles in cellular processes. Several studies have reported that 14-3-3γ, one of the 14-3-3 protein isoforms, is associated with neurological and psychiatric disorders, but the role of 14-3-3γ in the pathophysiology of brain diseases is unclear. Although studies have been conducted on the relationship between 14-3-3γ protein and Parkinson’s disease (PD), a common neurodegenerative disorder with severe motor symptoms such as bradykinesia and rigidity, a direct connection remains to be elucidated. We recently showed that adult heterozygous 14-3-3γ knockout mice are hyperactive and exhibit anxiety-like behavior. In this study, we further characterized the molecular and behavioral changes in aged 14-3-3γ heterozygous mice to investigate the role of 14-3-3γ in the brain. We observed decreased dopamine levels and altered dopamine metabolism in the brains of these mice, including changes in the phosphorylation of proteins implicated in PD pathology. Furthermore, we confirmed that they displayed PD symptom-like behavioral deficits, such as impaired motor coordination and decreased ability to the nest-building activity. These findings suggest an association between 14-3-3γ dysfunction and PD pathophysiology.

Sensorimotor integration and motor learning during a novel force-matching task in young adults with attention-deficit/hyperactivity disorder.

Attention-Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder that exhibits unique neurological and behavioral characteristics. Those with ADHD often have noted impairments in motor performance and coordination, including during tasks that require force modulation. The present study provides insight into the role of altered neural processing and SMI in response to a motor learning paradigm requiring force modulation and proprioception, that previous literature has suggested to be altered in those with ADHD, which can also inform our understanding of the neurophysiology underlying sensorimotor integration (SMI) in the general population. Adults with ADHD (n = 15) and neurotypical controls (n = 15) performed a novel force-matching task, where participants used their right-thumb to match a trace template that varied from 2-12% of their Abductor Pollicis Brevis maximum voluntary contraction. This motor task was completed in pre, acquisition, and post blocks. Participants also completed a retention test 24 h later. Median nerve somatosensory-evoked potentials (SEPs) were collected pre and post motor acquisition. SEPs were stimulated at two frequencies, 2.47 Hz and 4.98 Hz, and 1,000 sweeps were recorded using 64-electrode electroencephalography (EEG) at 2,048 Hz. SEP amplitude changes were normalized to each participant's baseline values for that peak. Both groups improved at post measures (ADHD: 0.85 ± 0.09; Controls: 0.85 ± 0.10), with improvements maintained at retention (ADHD: 0.82 ± 0.11; Controls: 0.82 ± 0.11). The ADHD group had a decreased N18 post-acquisition (0.87 ± 0.48), while the control N18 increased (1.91 ± 1.43). The N30 increased in both groups, with a small increase in the ADHD group (1.03 ± 0.21) and a more pronounced increase in controls (1.15 ± 0.27). Unique neural differences between groups were found after the acquisition of a novel force-matching motor paradigm, particularly relating to the N18 peak. The N18 differences suggest that those with ADHD have reduced olivary-cerebellar-M1 inhibition when learning a novel motor task dependent on force-modulation, potentially due to difficulties integrating the afferent feedback necessary to perform the task. The results of this work provide evidence that young adults with ADHD have altered proprioceptive processing when learning a novel motor task when compared to neurotypical controls.

Medical Cannabis sativa (Marijuana or drug type): Psychoactive molecule, Δ9-Tetrahydrocannabinol (Δ9-THC)

This review paper highlights about Medical Cannabis sativa (Marijuana or drug type) containing psychoactive molecule, Δ9-Tetrahydrocannabinol (Δ9-THC) as a part of educational awareness programme in India. Cannabis sativa and Cannabis indica were originally a native of India growing as a wild notorious noxious weed in the Indian Himalayan region. Marijuana (Charas, Ganja and Bhang in India) is a mind-altering (psychoactive) drug, produced by the Cannabis sativa plant. Marijuana (Charas, Ganja or Bhang drink in India) is an illicit drug containing very high levels (25-35%) of narcotic psychoactive molecule, Δ9-Tetrahydrocannabinol (Δ9-THC) is banned and prohibited in India. Import, export, local sales and cultivation of Cannabis are illegal and prohibited in India. Phytocannabinoids (Δ9-Tetrahydrocannabinol-Δ9-THC, and Cannabidiol- CBD) have attained a global attention recently due to the therapeutic potentials in Parkinson’s disease, Schizophrenia, cancers, pain, anxiety, depression other neurological disorders as well as the Food and Drug Administration (FDA) approval of Epidiolex for Dravet syndrome and Lennox-Gauss Syndrome. Δ9-Tetrahydrocannabinol (Δ9-THC) is known as the substance that makes a person feel a “high,” while Cannabidiol (CBD) often promotes a feeling of relaxation. However, the adverse effects of Marijuana (medicinal cannabis) comes from studies of recreational users of marijuana led to the impaired short-term memory; impaired motor coordination; altered judgment; and paranoia or psychosis at high doses. The quality control of Cannabis products, contamination and adulteration of Cannabis products in Cannabis industry is another major issue. Therefore, a detailed study with clinical trials is warranted and this knowledge should be shared and explained to the customers.

Construction and evaluation of an alcohol vapor chamber system.

An increasing number of studies demonstrated that alcohol vapor chamber is an effective way to model physical signs of alcohol use disorders. Although researchers are developing different vapor chambers to study chronic alcohol exposure model worldwide, few studies build and modify their own vapor chambers in China. Here, we designed and established an alcohol vapor chamber system for small animals. We described a paradigm showing how to control and monitor alcohol concentration in whole system. The vapor chamber system with several advantages including accommodating up to ten standard mouse cages. Furthermore, the system was tested by evaluating the blood alcohol concentration and neuron injury in mice. Importantly, the alcohol withdrawal after vapor exposure caused motor coordination impairment, anxiolytic- and depression-like behavior. Finally, the N-methyl-D-aspartate receptor (NMDAR)-mediated glutamatergic transmissions in the medial prefrontal cortex was changed after alcohol vapor exposure-induced behaviors. The frequency and amplitude of spontaneous excitatory postsynaptic currents between control and alcohol groups were not different, suggesting that alcohol exposure-induced behaviors are associated with the change in NMDAR response. Taken together, the new alcohol vapor chamber system was constructed, which would help to research the relationship between the stable alcohol exposure and withdrawal behaviors and to study chronic alcohol exposure-induced disorders in China.